Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

The Food and Drug Administration has approved ustekinumab-aauz (Otulfi), a biosimilar that references Johnson & Johnson’s ustekinumab (Stelara).

This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:

• Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• Patients 6 years or older with active psoriatic arthritis
• Adult patients with moderately to severely active Crohn’s disease
• Adult patients with moderately to severely active ulcerative colitis

Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).

The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”

Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-aauz (Otulfi), a biosimilar that references Johnson & Johnson’s ustekinumab (Stelara).

This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:

• Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• Patients 6 years or older with active psoriatic arthritis
• Adult patients with moderately to severely active Crohn’s disease
• Adult patients with moderately to severely active ulcerative colitis

Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).

The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”

Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-aauz (Otulfi), a biosimilar that references Johnson & Johnson’s ustekinumab (Stelara).

This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:

• Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• Patients 6 years or older with active psoriatic arthritis
• Adult patients with moderately to severely active Crohn’s disease
• Adult patients with moderately to severely active ulcerative colitis

Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).

The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”

Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).

A version of this article first appeared on Medscape.com.

COPENHAGEN — Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

COPENHAGEN — Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

COPENHAGEN — Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

The experimental monoclonal antibody tulisokibart safely induced clinical remission in a phase 2 randomized trial of moderately to severely active ulcerative colitis (UC).

In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).

The incidence of adverse events was similar in both arms, and most events were mild.

Courtesy Icahn School of Medicine at Mount Sinai

The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine. 

“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases. 

“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.

Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”

He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.

In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.” 
 

Why Target TL1A?

Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).

“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.

With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years. 

The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.

Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.” 
 

Earlier Application?

“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies. 

Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.

The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.

A version of this article appeared on Medscape.com.

The experimental monoclonal antibody tulisokibart safely induced clinical remission in a phase 2 randomized trial of moderately to severely active ulcerative colitis (UC).

In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).

The incidence of adverse events was similar in both arms, and most events were mild.

Courtesy Icahn School of Medicine at Mount Sinai

The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine. 

“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases. 

“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.

Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”

He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.

In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.” 
 

Why Target TL1A?

Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).

“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.

With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years. 

The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.

Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.” 
 

Earlier Application?

“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies. 

Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.

The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.

A version of this article appeared on Medscape.com.

The experimental monoclonal antibody tulisokibart safely induced clinical remission in a phase 2 randomized trial of moderately to severely active ulcerative colitis (UC).

In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).

The incidence of adverse events was similar in both arms, and most events were mild.

Courtesy Icahn School of Medicine at Mount Sinai

The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine. 

“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases. 

“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.

Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”

He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.

In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.” 
 

Why Target TL1A?

Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).

“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.

With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years. 

The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.

Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.” 
 

Earlier Application?

“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies. 

Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.

The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.

A version of this article appeared on Medscape.com.

For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

For patients with intermediate- or low-risk localized prostate cancer, intensity-modulated radiation therapy (IMRT) and proton beam therapy are both safe and effective options, according to results of the phase 3 randomized controlled PARTIQoL trial.

With both techniques, disease control rates were over 90%, with virtually no difference in bowel function or other quality-of-life ratings after 2 years, reported Jason Efstathiou, MD, PhD, with Massachusetts General Hospital, Boston, at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“This is a tremendous study [that] really shows us we have two great options, with equal results across the board for both control rates and toxicity rates,” said Sameer Keole, MD, incoming ASTRO president, during a press briefing.

“These control rates are phenomenal, and the complication rates were very low,” continued Dr. Keole, with the Mayo Clinic in Phoenix, Arizona. “I think men can go and seek definitive treatment when it’s appropriate with a radiation oncologist and know that whether it’s proton therapy or IMRT; it’s an excellent treatment option.”

Overall, about 70% of new cases of prostate cancer each year are localized disease, which represents about 200,000 patients in the United States each year, Dr. Efstathiou explained. These patients have several treatment options, including different choices for external beam radiation therapy.

“Because many of these patients are going to survive their cancer and live many years after treatment, quality of life becomes paramount because they’re at risk for long-term posttreatment morbidity,” Dr. Efstathiou said. “Quality of life will inform their decision-making.”

Dr. Efstathiou noted that proton beam therapy comes with certain dosimetric advantages with the potential to reduce morbidity and improve cancer outcomes, but it is generally more resource intensive and costly than IMRT.

The PARTIQoL multicenter, phase 3, randomized trial compared patient-reported quality of life after external beam radiation using either IMRT or proton beam therapy to determine whether one performs better on the local control and toxicity fronts.

After stratifying by institution, age (< 65 years vs ≥ 65 years), rectal spacer use (no vs yes), and moderate hypofractionation (no vs yes), participants were randomized to either proton beam therapy or IMRT.

Patients were followed longitudinally for 60 months after completing radiotherapy. The primary endpoint was bowel function at 24 months using the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary outcomes included urinary and erectile function, sexual function, toxicity and efficacy, or disease control endpoints.

Of the 450 patients randomized, 221 of 226 (97.8%) randomized to proton beam therapy and 216 of 224 (96.4%) randomized to IMRT started on their respective treatments, and 167 and 162, respectively, completed the EPIC at 24 months. This represents about a 27% rate of missing data, which “was much better than anticipated,” Dr. Efstathiou noted.

For the primary endpoint, there was no difference between proton beam therapy and IMRT in mean change of the EPIC bowel score at 24 months, with both treatment groups showing only a small, clinically nonrelevant decline from baseline. There was only about a 2% decrease on a 100-point scale in bowel quality of life after 2 years, Dr. Efstathiou reported.

Similarly, the team noted no difference in bowel function at earlier or later time points. “We see some small fluctuations, but at no time point did these reach statistical significance,” he noted.

There were also no differences observed in the other domains at any point, including urinary incontinence, urinary irritation, or sexual function.

Turning to disease control, Dr. Efstathiou and colleagues found no difference between the two groups in progression-free survival. The progression-free survival rate was 99% at 24 months and 93.7% at 60 months with IMRT, compared with 98.1% at 24 months and 93.4% at 60 months with proton beam therapy.

When looking at key subgroups or factors, the team reported no sustained difference in any quality-of-life domain or in cancer control.

Patient monitoring over a longer follow-up period is ongoing. Dr. Efstathiou noted that the PARTIQoL trial was limited to localized low- and intermediate-risk prostate cancer patients receiving either conventionally or moderately hypofractionated therapy. The trial also did not address the full range of disease scope, including higher risk disease, nodal therapy, concurrent use of hormonal therapy or other systemic therapy, local recurrent situations, or retreatment situations.

Dr. Efstathiou noted that because both proton therapy and IMRT continue to evolve, there is ongoing work to optimize the delivery of both.

Overall, the PARTIQoL trial results demonstrate “equivalent outcomes, with superb cancer control rates and extremely low toxicity from both treatments,” Jessica Karen Wong, MD, MEng, who wasn’t involved in the study, told this news organization.

“Both are excellent treatments for low- and intermediate-risk prostate cancer patients,” said Dr. Wong, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “This study corroborates prior single and multi-institutional experiences with the statistical power and rigorous methods of a clinical trial. Dr Efstathiou and authors should be commended for this comprehensive and well-run trial.”

Discussant for the study, Curtiland Deville, MD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, agreed that patients in the trial did “exceedingly well,” regardless of whether patients received IMRT or proton therapy.

Dr. Deville said the “fundamental question regarding the use of proton therapy for prostate cancer remains — is there a clinical benefit to protons that justifies their increased costs in this setting? In a cost-neutral setting, it may still be considered very reasonable to deliver proton therapy for prostate cancer.”

In his view, this study is “practice informing” but not yet “practice changing as we await the imminent findings of the COMPARE trial,” which uses a pragmatic design powered to assess the co-primary patient-reported outcome endpoints of EPIC bowel summary, urinary function, and sexual function scores at 2 years, and which enrolled over 2500 patients.

The study has no commercial funding. Dr. Efstathiou disclosed various relationships with IBA Proton Therapy, Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Lantheus/Progenics, Astellas/Pfizer, Elekta, Uptodate, Merck, Roivant Pharma, Myovant Sciences, EMD Serono, Bayer Healthcare, Janssen, Pfizer, Progenics Pharmaceuticals, Gilead, Angiodynamics, and Clarity Pharmaceuticals. Dr. Keole and Dr. Wong had no relevant disclosures. Dr. Deville is deputy editor of the ASTRO Red Journal.

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the annual World Conference on Lung Cancer on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Dr. Zhu said.
 

Different Approaches in ESCC

Dr. Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Dr. Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.
 

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Dr. Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Dr. Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Dr. Zhu declared no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

A version of this article first appeared on Medscape.com.

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

A version of this article first appeared on Medscape.com.

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.
 

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
 

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
 

A version of this article first appeared on Medscape.com.