Psoriatic Arthritis ICYMI

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.

• Exploring new guidelines and scientific advances
• ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
• Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
• Biologics may delay psoriatic arthritis
• AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
• Specific markers detect psoriatic disease inflammation without elevated CRP
• Beyond PASI 100: Striving for molecular clearance
• Ultrasound improves specificity of psoriatic arthritis referrals
• Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
• New psoriasis guidelines focus on topical and alternative treatments, and severity measures
• Psoriasis topical combination maintenance strategy hits mark at 1 year

Read the supplement.

Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.

• Exploring new guidelines and scientific advances
• ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
• Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
• Biologics may delay psoriatic arthritis
• AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
• Specific markers detect psoriatic disease inflammation without elevated CRP
• Beyond PASI 100: Striving for molecular clearance
• Ultrasound improves specificity of psoriatic arthritis referrals
• Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
• New psoriasis guidelines focus on topical and alternative treatments, and severity measures
• Psoriasis topical combination maintenance strategy hits mark at 1 year

Read the supplement.

Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.

• Exploring new guidelines and scientific advances
• ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
• Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
• Biologics may delay psoriatic arthritis
• AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
• Specific markers detect psoriatic disease inflammation without elevated CRP
• Beyond PASI 100: Striving for molecular clearance
• Ultrasound improves specificity of psoriatic arthritis referrals
• Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
• New psoriasis guidelines focus on topical and alternative treatments, and severity measures
• Psoriasis topical combination maintenance strategy hits mark at 1 year

Read the supplement.

Patients aged 2 years and older now have intravenous golimumab (Simponi Aria) as an option to treat active polyarticular-course juvenile idiopathic arthritis (pJIA) or psoriatic arthritis (PsA) after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.

Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m², also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.

The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.

The full prescribing information for intravenous golimumab can be found on the FDA website.

jevans@mdedge.com

Patients aged 2 years and older now have intravenous golimumab (Simponi Aria) as an option to treat active polyarticular-course juvenile idiopathic arthritis (pJIA) or psoriatic arthritis (PsA) after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.

Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m², also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.

The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.

The full prescribing information for intravenous golimumab can be found on the FDA website.

jevans@mdedge.com

Patients aged 2 years and older now have intravenous golimumab (Simponi Aria) as an option to treat active polyarticular-course juvenile idiopathic arthritis (pJIA) or psoriatic arthritis (PsA) after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.

Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m², also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.

The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.

The full prescribing information for intravenous golimumab can be found on the FDA website.

jevans@mdedge.com

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Initiating treatment with the interleukin-12/23p40–targeting monoclonal antibody ustekinumab may trigger early severe cardiovascular events (SCEs) in susceptible patients, according to a large French case-time-control analysis.

Investigators led by Florence Poizeau, MD, of the department of dermatology at Rennes (France) University Hospital, found high-risk patients had more than four times the risk of an acute SCE in the 6 months after starting treatment. Although ustekinumab (Stelara) effectively treats moderate to severe psoriasis, psoriatic arthritis (PsA), and Crohn’s disease (indications approved by the Food and Drug Administration), the early months after ustekinumab initiation may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17, the group reported in JAMA Dermatology.

The observational study drew on France’s 66 million–registrant health insurance database to identify all patients exposed to ustekinumab between April 1, 2010, and Dec. 31, 2016. Classified by high or low cardiovascular risk level, ustekinumab recipients served as their own controls, being compared during two time windows: the risk period covered the 6 months after initiating treatment and leading up to the SCE, defined as acute coronary syndrome (ACS) or stroke, while a reference period spanned the 6-12 months leading up to the risk period.

In the statistical analysis of 9,290 ustekinumab-exposed patients (mean age 43 years, 52% male), conducted from September 2017 to July 2018, 7,588 (82%) received ustekinumab for psoriasis or PsA, and 724 (8%) for Crohn’s disease. (The remaining indications were for psoriasis or PsA and Crohn’s disease, or were undetermined.)

Of these patients, 98 experienced SCEs (52 with ACS admitted to the ICU and 46 with strokes). In patients deemed at high cardiovascular risk – those with two risk factors or a personal history of atherosclerotic disease – there was a statistically significant association between starting ustekinumab and SCE occurrence, for an odds ratio of 4.17 (95% confidence interval, 1.19-14.59). In contrast, no such association emerged in ustekinumab users at low cardiovascular risk, for an OR of 0.30 (95% CI, 0.03-3.13). The OR for all was 2.41 (95% CI, 0.83-7.01).

Of the 98 patients included in the final case-time-control analysis, 62 were men (63%), the median age was 57 years, and 76 (78%) were at high cardiovascular risk. A total of 89 patients (91%) had psoriasis, four (4%) had Crohn’s disease, and two (2%) had both.

The investigators also did an analysis including these 98 patients plus 13 patients with ACS who were not hospitalized in an ICU, and 68 with unstable angina, for a total of 179. In this group, the ORs for SCE were 1.75 (95% CI, 0.86-3.56) overall, compared with 3.20 (95% CI, 1.29-7.92) among those at high cardiovascular risk and 0.21 (95% CI, 0.02-1.69) among those at low cardiovascular risk.

The Rennes investigators’ decision to focus on early SCEs stemmed in part from a meta-analysis of randomized clinical trials that reported a possible excess of early SCEs in adults exposed to anti–IL-12/23p40 antibodies, which at that time included the now-discontinued experimental antibody briakinumab. Briakinumab trials were aborted and the drug was never brought to market, leaving ustekinumab as the only antibody of this type.

The finding of “an association between ustekinumab initiation and SCE among patients with cardiovascular risk factors suggests the need for caution regarding the prescription of ustekinumab in this population,” Dr. Poizeau and colleagues wrote. The risk “seems to concern patients with psoriasis” rather than Crohn’s disease, which may be related to the older age and greater cardiovascular risk of the former. “A close collaboration between cardiologists and biologic prescribers could be beneficial to evaluate the risk of SCEs for patients who are receiving ustekinumab,” they added, recommending further research into the physiopathological mechanisms of action.

Offering a U.S. clinician’s perspective on the French study, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, called the findings “unique and interesting with very robust odds ratios. These posttreatment associations have actually been a big area of research over the past decade but not with such defined time periods.”

No significant increases in risk have been seen with other biologics, Dr. Fernandez added, with the exception of briakinumab. “But still, the current study does not definitively answer the question whether ustekinumab can trigger acute events within 6 months of treatment. There’s smoke, but we haven’t clearly seen a fire.”

As to ustekinumab’s possible pathogenic mechanism of action, Dr. Fernandez pointed to data suggesting that IL-17A can be stabilizing to atherosclerotic plaques. “So there’s a hypothesis that blocking the 17/23 pathway may destabilize plaques and make patients more prone to acute cardiovascular events.”

In other comments from clinicians not involved in the study, Seoyoung Kim, MD, ScD, MSCE, director of the program in rheumatologic, immunologic, and musculoskeletal pharmacoepidemiology (PRIME) at Brigham and Women’s Hospital, Boston, noted that, while the investigators controlled for the trend over time and their design choice included time-fixed covariates such as age, sex, and family history within individuals, the case-crossover study could not control for time-varying confounders within individuals.

“In other words, it’s possible that some of the patients had a lot more disease activity and systemic inflammation and used more NSAIDs, steroids, and other medications potentially related to cardiovascular risk a few months before they started ustekinumab, compared with 6-12 months prior,“ Dr. Kim said in an interview. “I would be curious to know if they would find the same thing or not if they studied a different type of biologic drug.”

She also pointed out that the number of outcomes overall was small, leading to imprecise estimates and wide confidence intervals.

Last year Dr. Kim and associates published a study comparing ustekinumab with tumor necrosis factor inhibitor therapy in younger psoriasis and psoriatic arthritis patients and found no difference between the two groups in major cardiovascular events or atrial fibrillation.

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, has more reservations about the findings. “The Poizeau study was methodologically flawed, making the results unreliable,” he said in an interview. “There is a breadth of data from clinical trials and observational studies that do not demonstrate an increased risk of major acute cardiovascular events with ustekinumab and the results of the Poizeau study should not impact clinical practice.”

In an interview, Mark G. Lebwohl, MD, professor and chairman of the department of dermatology and chief for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York, said that, in his view, the investigators used early reports of a small number cardiovascular events to look at the issue from a faulty perspective, and hence their findings would have no impact on his clinical practice.

“This study looked at the issue incorrectly. It looked at people put on drug who already had two risk factors for heart attack. And psoriasis itself is a third risk factor,” he said. “So lo and behold, big surprise, some of them had cardiovascular events.”

Dr. Lebwohl noted that a wealth of carefully compiled data has found no increase over time in cardiovascular events with this drug in psoriasis patients. The risk of cardiovascular events actually goes down with time because of the drug’s anti-inflammatory effects.

Dr. Fernandez takes a more positive view of the French findings. “The data certainly support the need for further research in this area,” he said in an interview, “and in the meantime this paper will probably make me extra cautious in using ustekinumab in those at significant risk.”

The French study was supported by a grant from the French National Agency for Medicines and Health Products Safety. Dr. Poizeau and seven coauthors had no disclosures. The remaining five reported disclosures that included receiving fees from AbbVie, Admiral, Amgen, Baxalta, Cologne, Dermavant, Eli Lilly, Janssen, Kyowa Kirin, Novartis, Mylan, Sun Pharmaceuticals, and UCB, as well as grants and personal fees from Boehringer Ingelheim, Leo Pharma, and Pfizer outside the submitted work, and personal fees from Pfizer, AbbVie, UCB Pharma, and Lilly during the conduct of the study. Dr. Fernandez reported consulting work for AbbVie and research grants from Novartis. Dr. Kim disclosed research grants from Brigham and Women’s Hospital and from Pfizer, Abbvie, Roche, and Bristol-Myers Squibb for unrelated studies. Dr. Gelfand reported varying financial ties to Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen Biologics, Regeneron, UCB, Sanofi, Pfizer, Celgene, OrthoDermatolgics, AbbVie, Novartis, and Eli Lilly. He is copatent holder of a treatment for cutaneous T-cell lymphoma. Dr. Lebwohl reported unpaid consulting for most manufacturers of psoriasis drugs, with all fees going directly to Mount Sinai.

Source: Poizeau F et al. JAMA Dermatol. 2020 Sep 9. doi: 10.1001/jamadermatol.2020.2977.
 

Initiating treatment with the interleukin-12/23p40–targeting monoclonal antibody ustekinumab may trigger early severe cardiovascular events (SCEs) in susceptible patients, according to a large French case-time-control analysis.

Investigators led by Florence Poizeau, MD, of the department of dermatology at Rennes (France) University Hospital, found high-risk patients had more than four times the risk of an acute SCE in the 6 months after starting treatment. Although ustekinumab (Stelara) effectively treats moderate to severe psoriasis, psoriatic arthritis (PsA), and Crohn’s disease (indications approved by the Food and Drug Administration), the early months after ustekinumab initiation may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17, the group reported in JAMA Dermatology.

The observational study drew on France’s 66 million–registrant health insurance database to identify all patients exposed to ustekinumab between April 1, 2010, and Dec. 31, 2016. Classified by high or low cardiovascular risk level, ustekinumab recipients served as their own controls, being compared during two time windows: the risk period covered the 6 months after initiating treatment and leading up to the SCE, defined as acute coronary syndrome (ACS) or stroke, while a reference period spanned the 6-12 months leading up to the risk period.

In the statistical analysis of 9,290 ustekinumab-exposed patients (mean age 43 years, 52% male), conducted from September 2017 to July 2018, 7,588 (82%) received ustekinumab for psoriasis or PsA, and 724 (8%) for Crohn’s disease. (The remaining indications were for psoriasis or PsA and Crohn’s disease, or were undetermined.)

Of these patients, 98 experienced SCEs (52 with ACS admitted to the ICU and 46 with strokes). In patients deemed at high cardiovascular risk – those with two risk factors or a personal history of atherosclerotic disease – there was a statistically significant association between starting ustekinumab and SCE occurrence, for an odds ratio of 4.17 (95% confidence interval, 1.19-14.59). In contrast, no such association emerged in ustekinumab users at low cardiovascular risk, for an OR of 0.30 (95% CI, 0.03-3.13). The OR for all was 2.41 (95% CI, 0.83-7.01).

Of the 98 patients included in the final case-time-control analysis, 62 were men (63%), the median age was 57 years, and 76 (78%) were at high cardiovascular risk. A total of 89 patients (91%) had psoriasis, four (4%) had Crohn’s disease, and two (2%) had both.

The investigators also did an analysis including these 98 patients plus 13 patients with ACS who were not hospitalized in an ICU, and 68 with unstable angina, for a total of 179. In this group, the ORs for SCE were 1.75 (95% CI, 0.86-3.56) overall, compared with 3.20 (95% CI, 1.29-7.92) among those at high cardiovascular risk and 0.21 (95% CI, 0.02-1.69) among those at low cardiovascular risk.

The Rennes investigators’ decision to focus on early SCEs stemmed in part from a meta-analysis of randomized clinical trials that reported a possible excess of early SCEs in adults exposed to anti–IL-12/23p40 antibodies, which at that time included the now-discontinued experimental antibody briakinumab. Briakinumab trials were aborted and the drug was never brought to market, leaving ustekinumab as the only antibody of this type.

The finding of “an association between ustekinumab initiation and SCE among patients with cardiovascular risk factors suggests the need for caution regarding the prescription of ustekinumab in this population,” Dr. Poizeau and colleagues wrote. The risk “seems to concern patients with psoriasis” rather than Crohn’s disease, which may be related to the older age and greater cardiovascular risk of the former. “A close collaboration between cardiologists and biologic prescribers could be beneficial to evaluate the risk of SCEs for patients who are receiving ustekinumab,” they added, recommending further research into the physiopathological mechanisms of action.

Offering a U.S. clinician’s perspective on the French study, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, called the findings “unique and interesting with very robust odds ratios. These posttreatment associations have actually been a big area of research over the past decade but not with such defined time periods.”

No significant increases in risk have been seen with other biologics, Dr. Fernandez added, with the exception of briakinumab. “But still, the current study does not definitively answer the question whether ustekinumab can trigger acute events within 6 months of treatment. There’s smoke, but we haven’t clearly seen a fire.”

As to ustekinumab’s possible pathogenic mechanism of action, Dr. Fernandez pointed to data suggesting that IL-17A can be stabilizing to atherosclerotic plaques. “So there’s a hypothesis that blocking the 17/23 pathway may destabilize plaques and make patients more prone to acute cardiovascular events.”

In other comments from clinicians not involved in the study, Seoyoung Kim, MD, ScD, MSCE, director of the program in rheumatologic, immunologic, and musculoskeletal pharmacoepidemiology (PRIME) at Brigham and Women’s Hospital, Boston, noted that, while the investigators controlled for the trend over time and their design choice included time-fixed covariates such as age, sex, and family history within individuals, the case-crossover study could not control for time-varying confounders within individuals.

“In other words, it’s possible that some of the patients had a lot more disease activity and systemic inflammation and used more NSAIDs, steroids, and other medications potentially related to cardiovascular risk a few months before they started ustekinumab, compared with 6-12 months prior,“ Dr. Kim said in an interview. “I would be curious to know if they would find the same thing or not if they studied a different type of biologic drug.”

She also pointed out that the number of outcomes overall was small, leading to imprecise estimates and wide confidence intervals.

Last year Dr. Kim and associates published a study comparing ustekinumab with tumor necrosis factor inhibitor therapy in younger psoriasis and psoriatic arthritis patients and found no difference between the two groups in major cardiovascular events or atrial fibrillation.

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, has more reservations about the findings. “The Poizeau study was methodologically flawed, making the results unreliable,” he said in an interview. “There is a breadth of data from clinical trials and observational studies that do not demonstrate an increased risk of major acute cardiovascular events with ustekinumab and the results of the Poizeau study should not impact clinical practice.”

In an interview, Mark G. Lebwohl, MD, professor and chairman of the department of dermatology and chief for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York, said that, in his view, the investigators used early reports of a small number cardiovascular events to look at the issue from a faulty perspective, and hence their findings would have no impact on his clinical practice.

“This study looked at the issue incorrectly. It looked at people put on drug who already had two risk factors for heart attack. And psoriasis itself is a third risk factor,” he said. “So lo and behold, big surprise, some of them had cardiovascular events.”

Dr. Lebwohl noted that a wealth of carefully compiled data has found no increase over time in cardiovascular events with this drug in psoriasis patients. The risk of cardiovascular events actually goes down with time because of the drug’s anti-inflammatory effects.

Dr. Fernandez takes a more positive view of the French findings. “The data certainly support the need for further research in this area,” he said in an interview, “and in the meantime this paper will probably make me extra cautious in using ustekinumab in those at significant risk.”

The French study was supported by a grant from the French National Agency for Medicines and Health Products Safety. Dr. Poizeau and seven coauthors had no disclosures. The remaining five reported disclosures that included receiving fees from AbbVie, Admiral, Amgen, Baxalta, Cologne, Dermavant, Eli Lilly, Janssen, Kyowa Kirin, Novartis, Mylan, Sun Pharmaceuticals, and UCB, as well as grants and personal fees from Boehringer Ingelheim, Leo Pharma, and Pfizer outside the submitted work, and personal fees from Pfizer, AbbVie, UCB Pharma, and Lilly during the conduct of the study. Dr. Fernandez reported consulting work for AbbVie and research grants from Novartis. Dr. Kim disclosed research grants from Brigham and Women’s Hospital and from Pfizer, Abbvie, Roche, and Bristol-Myers Squibb for unrelated studies. Dr. Gelfand reported varying financial ties to Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen Biologics, Regeneron, UCB, Sanofi, Pfizer, Celgene, OrthoDermatolgics, AbbVie, Novartis, and Eli Lilly. He is copatent holder of a treatment for cutaneous T-cell lymphoma. Dr. Lebwohl reported unpaid consulting for most manufacturers of psoriasis drugs, with all fees going directly to Mount Sinai.

Source: Poizeau F et al. JAMA Dermatol. 2020 Sep 9. doi: 10.1001/jamadermatol.2020.2977.
 

Initiating treatment with the interleukin-12/23p40–targeting monoclonal antibody ustekinumab may trigger early severe cardiovascular events (SCEs) in susceptible patients, according to a large French case-time-control analysis.

Investigators led by Florence Poizeau, MD, of the department of dermatology at Rennes (France) University Hospital, found high-risk patients had more than four times the risk of an acute SCE in the 6 months after starting treatment. Although ustekinumab (Stelara) effectively treats moderate to severe psoriasis, psoriatic arthritis (PsA), and Crohn’s disease (indications approved by the Food and Drug Administration), the early months after ustekinumab initiation may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17, the group reported in JAMA Dermatology.

The observational study drew on France’s 66 million–registrant health insurance database to identify all patients exposed to ustekinumab between April 1, 2010, and Dec. 31, 2016. Classified by high or low cardiovascular risk level, ustekinumab recipients served as their own controls, being compared during two time windows: the risk period covered the 6 months after initiating treatment and leading up to the SCE, defined as acute coronary syndrome (ACS) or stroke, while a reference period spanned the 6-12 months leading up to the risk period.

In the statistical analysis of 9,290 ustekinumab-exposed patients (mean age 43 years, 52% male), conducted from September 2017 to July 2018, 7,588 (82%) received ustekinumab for psoriasis or PsA, and 724 (8%) for Crohn’s disease. (The remaining indications were for psoriasis or PsA and Crohn’s disease, or were undetermined.)

Of these patients, 98 experienced SCEs (52 with ACS admitted to the ICU and 46 with strokes). In patients deemed at high cardiovascular risk – those with two risk factors or a personal history of atherosclerotic disease – there was a statistically significant association between starting ustekinumab and SCE occurrence, for an odds ratio of 4.17 (95% confidence interval, 1.19-14.59). In contrast, no such association emerged in ustekinumab users at low cardiovascular risk, for an OR of 0.30 (95% CI, 0.03-3.13). The OR for all was 2.41 (95% CI, 0.83-7.01).

Of the 98 patients included in the final case-time-control analysis, 62 were men (63%), the median age was 57 years, and 76 (78%) were at high cardiovascular risk. A total of 89 patients (91%) had psoriasis, four (4%) had Crohn’s disease, and two (2%) had both.

The investigators also did an analysis including these 98 patients plus 13 patients with ACS who were not hospitalized in an ICU, and 68 with unstable angina, for a total of 179. In this group, the ORs for SCE were 1.75 (95% CI, 0.86-3.56) overall, compared with 3.20 (95% CI, 1.29-7.92) among those at high cardiovascular risk and 0.21 (95% CI, 0.02-1.69) among those at low cardiovascular risk.

The Rennes investigators’ decision to focus on early SCEs stemmed in part from a meta-analysis of randomized clinical trials that reported a possible excess of early SCEs in adults exposed to anti–IL-12/23p40 antibodies, which at that time included the now-discontinued experimental antibody briakinumab. Briakinumab trials were aborted and the drug was never brought to market, leaving ustekinumab as the only antibody of this type.

The finding of “an association between ustekinumab initiation and SCE among patients with cardiovascular risk factors suggests the need for caution regarding the prescription of ustekinumab in this population,” Dr. Poizeau and colleagues wrote. The risk “seems to concern patients with psoriasis” rather than Crohn’s disease, which may be related to the older age and greater cardiovascular risk of the former. “A close collaboration between cardiologists and biologic prescribers could be beneficial to evaluate the risk of SCEs for patients who are receiving ustekinumab,” they added, recommending further research into the physiopathological mechanisms of action.

Offering a U.S. clinician’s perspective on the French study, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, called the findings “unique and interesting with very robust odds ratios. These posttreatment associations have actually been a big area of research over the past decade but not with such defined time periods.”

No significant increases in risk have been seen with other biologics, Dr. Fernandez added, with the exception of briakinumab. “But still, the current study does not definitively answer the question whether ustekinumab can trigger acute events within 6 months of treatment. There’s smoke, but we haven’t clearly seen a fire.”

As to ustekinumab’s possible pathogenic mechanism of action, Dr. Fernandez pointed to data suggesting that IL-17A can be stabilizing to atherosclerotic plaques. “So there’s a hypothesis that blocking the 17/23 pathway may destabilize plaques and make patients more prone to acute cardiovascular events.”

In other comments from clinicians not involved in the study, Seoyoung Kim, MD, ScD, MSCE, director of the program in rheumatologic, immunologic, and musculoskeletal pharmacoepidemiology (PRIME) at Brigham and Women’s Hospital, Boston, noted that, while the investigators controlled for the trend over time and their design choice included time-fixed covariates such as age, sex, and family history within individuals, the case-crossover study could not control for time-varying confounders within individuals.

“In other words, it’s possible that some of the patients had a lot more disease activity and systemic inflammation and used more NSAIDs, steroids, and other medications potentially related to cardiovascular risk a few months before they started ustekinumab, compared with 6-12 months prior,“ Dr. Kim said in an interview. “I would be curious to know if they would find the same thing or not if they studied a different type of biologic drug.”

She also pointed out that the number of outcomes overall was small, leading to imprecise estimates and wide confidence intervals.

Last year Dr. Kim and associates published a study comparing ustekinumab with tumor necrosis factor inhibitor therapy in younger psoriasis and psoriatic arthritis patients and found no difference between the two groups in major cardiovascular events or atrial fibrillation.

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, has more reservations about the findings. “The Poizeau study was methodologically flawed, making the results unreliable,” he said in an interview. “There is a breadth of data from clinical trials and observational studies that do not demonstrate an increased risk of major acute cardiovascular events with ustekinumab and the results of the Poizeau study should not impact clinical practice.”

In an interview, Mark G. Lebwohl, MD, professor and chairman of the department of dermatology and chief for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York, said that, in his view, the investigators used early reports of a small number cardiovascular events to look at the issue from a faulty perspective, and hence their findings would have no impact on his clinical practice.

“This study looked at the issue incorrectly. It looked at people put on drug who already had two risk factors for heart attack. And psoriasis itself is a third risk factor,” he said. “So lo and behold, big surprise, some of them had cardiovascular events.”

Dr. Lebwohl noted that a wealth of carefully compiled data has found no increase over time in cardiovascular events with this drug in psoriasis patients. The risk of cardiovascular events actually goes down with time because of the drug’s anti-inflammatory effects.

Dr. Fernandez takes a more positive view of the French findings. “The data certainly support the need for further research in this area,” he said in an interview, “and in the meantime this paper will probably make me extra cautious in using ustekinumab in those at significant risk.”

The French study was supported by a grant from the French National Agency for Medicines and Health Products Safety. Dr. Poizeau and seven coauthors had no disclosures. The remaining five reported disclosures that included receiving fees from AbbVie, Admiral, Amgen, Baxalta, Cologne, Dermavant, Eli Lilly, Janssen, Kyowa Kirin, Novartis, Mylan, Sun Pharmaceuticals, and UCB, as well as grants and personal fees from Boehringer Ingelheim, Leo Pharma, and Pfizer outside the submitted work, and personal fees from Pfizer, AbbVie, UCB Pharma, and Lilly during the conduct of the study. Dr. Fernandez reported consulting work for AbbVie and research grants from Novartis. Dr. Kim disclosed research grants from Brigham and Women’s Hospital and from Pfizer, Abbvie, Roche, and Bristol-Myers Squibb for unrelated studies. Dr. Gelfand reported varying financial ties to Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen Biologics, Regeneron, UCB, Sanofi, Pfizer, Celgene, OrthoDermatolgics, AbbVie, Novartis, and Eli Lilly. He is copatent holder of a treatment for cutaneous T-cell lymphoma. Dr. Lebwohl reported unpaid consulting for most manufacturers of psoriasis drugs, with all fees going directly to Mount Sinai.

Source: Poizeau F et al. JAMA Dermatol. 2020 Sep 9. doi: 10.1001/jamadermatol.2020.2977.
 

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.