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EADV: Pursuing ‘clear’ in psoriasis worthwhile, expert says
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
AT THE EADV CONGRESS
Key clinical point: A Physician Global Assessment of “clear” is worth striving for in psoriasis patients because it represents a clinically important lesser level of disease than “almost clear.”
Major finding: Fourteen percent of psoriasis patients with an on-treatment physician assessment of “almost clear” had at least moderately impaired health care quality of life, compared with 6.4% of those rated “clear.”
Data source: A secondary pooled analysis of quality of life–related outcomes among psoriasis patients rated “clear” as opposed to “almost clear” at week 12 of three phase III double-blind randomized trials of the interleukin-17 inhibitor brodalumab.
Disclosures: The presenter reported receiving research support from Amgen, which sponsored the study.
Anti-TNF therapy can continue for IBD patients with skin lesions
Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.
In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.
Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.
“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.
Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).
Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.
In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.
Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.
“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.
Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).
Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.
In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.
Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.
“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.
Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).
Steroid use down, biologic use rising in pregnancies of women with rheumatic disease
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Women with lupus and other rheumatic diseases used fewer steroids during pregnancy over a 12-year period, while use of biologic agents increased over time.
Major finding: Steroid use dropped from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while biologic use increased from 5.1 per 100 to 16.6 (P less than .001 for both).
Data source: Private and public insurance records, including prescription filling data, for 2,645 U.S. women with lupus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis who gave birth between 2001 and 2012.
Disclosures: The study received no outside funding. Two coauthors reported financial relationships with pharmaceutical manufacturers.
Psoriasis cohort reveals high arthritis risk
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Incidence of psoriatic arthritis is higher among psoriasis patients than previously estimated.
Major finding: Annual incidence rate was 2.7 (95% confidence interval 2.1, 3.6) PsA cases per 100 psoriasis patients; significant predictors included disease severity, nail pitting, low education, and uveitis.
Data source: A prospective cohort study of 464 psoriasis patients without arthritis at baseline, followed for 8 years.
Disclosures: Krembil Foundation, Canadian Institutes of Health Research, and The Arthritis Society sponsored the study.
EADV: New long-term data on biologics for pediatric psoriasis ‘encouraging’
COPENHAGEN – The longest-ever clinical trials of etanercept and adalimumab for pediatric psoriasis show reassuring maintenance of efficacy, coupled with safety and tolerability profiles similar to what has been seen in long-term trials in adults, investigators reported at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Richard G. Langley presented outcomes from a 5-year open-label extension of an initial 12-week, multicenter, double-blind, randomized trial of etanercept or placebo in children and adolescents with moderate to severe chronic plaque psoriasis. The primary results were published more than 7 years ago (N Engl J Med. 2008 Jan 17;358[3]:241-51).
“This is the largest and longest follow-up of any biologic in children and adolescents to date. I think it’s encouraging data and should be reassuring to those of us who are managing this important population of pediatric patients in our conversations with parents and families,”said Dr. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
In the original 211-patient study, 57% of patients receiving etanercept (Enbrel) once weekly at 0.8 mg/kg to a maximum of 50 mg achieved a PASI 75 response at week 12, and 27% had a PASI 90. In the 69 patients who completed the full 264 weeks of follow-up, those response rates remained essentially unchanged.
Dr. Langley was quick to point out that this was an as-observed analysis, meaning results were counted only in those patients still participating at week 264. While conceding that the two-thirds dropout rate is an important study limitation, he added: “Notwithstanding that, what matters to us in the clinic are the patients we continue to treat and how they’re responding.”
Of note, most study discontinuations didn’t result from loss of response or adverse events, they were due to withdrawal of consent by families in which the patient began the study as a cooperative child and who as time went by turned into an independent and often willful teenager, he said.
No new safety signals arose over the course of 5 years. There were no opportunistic infections, no malignancies. The most common adverse events were the same ones seen in the original short-term study: upper respiratory infections, nasopharyngitis, and headaches. There was only one serious adverse event deemed by investigators as ‘possibly related’ to etanercept therapy: a case of cellulitis.
Separately, Dr. Diamant Thaci and Dr. Kim A. Papp presented 52-week outcomes for different aspects of the pivotal phase III randomized trial which earlier in 2015 earned adalimumab (Humira) European Commission marketing approval as the first biologic agent indicated for treatment of children as young as age 4 years, as well as for adolescents. The multi-arm trial included 114 patients aged 4-17 years with moderate to severe plaque psoriasis.
Dr. Thaci reported on the 37 subjects initially randomized double-blind to 16 weeks of oral methotrexate at 0.1-0.4 mg/kg weekly. The 19 patients (51%) who were deemed nonresponders to methotrexate because of inadequate PASI response at week 16 were then switched to open-label adalimumab at 0.8 mg/kg every other week for the remainder of the 52 weeks.
After 16 weeks on adalimumab, the methotrexate nonresponders had a PASI 75 of 90% and a PASI 90 of 74%, and 79% of the subjects were rated clear or almost clear by Physician’s Global Assessment. At week 52, the PASI 75 rate was 79%, the PASI 90 rate was 58%, and 68% of patients were rated clear or almost clear, according to Dr. Thaci of University Hospital Schleswig-Holstein, in L<scaps>ü</scaps>beck, Germany.
The side effects of methotrexate and adalimumab were similar to those seen in adults. There were no serious adverse events. The infections that occurred during adalimumab therapy were “very banal things,” mostly nasopharyngitis and upper respiratory tract infections, the dermatologist said. There were no opportunistic infections, malignancies, or cases of tuberculosis during the phase III study.
This was an important analysis because it recapitulates daily clinical practice, he explained. In most of the world, when dermatologists deem it time for systemic therapy, they generally start out with methotrexate, reserving biologics for second-line therapy because of the cost.
Dr. Papp reported on 39 patients on adalimumab at 0.4 mg/kg every other week, and 38 on 0.8 mg/kg every other week throughout the 52-week study. The response rate was essentially a flat line from week 16 to week 52, with PASI 75s of 44% at week 16 and 50% at week 52 in the low-dose group, and 58% and 56% in the high-dose group. Half of patients on 0.4 mg/kg were clear or almost clear at week 52, as were 56% on 0.8 mg/kg.
There was a nonsignificant trend for an increasing infection rate with greater exposure to adalimumab, which will require evaluation during the ongoing follow-up beyond 52 weeks, said Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
“I think what’s gratifying about this is we see that these children actually have a robust response and that response is maintained over a full year of treatment, which is reassuring because that reflects what we’ve seen in the adult population as well,” he said.
Dr. Papp and Dr. Thaci receive research funding and serve as scientific advisers to AbbVie, which sponsored the adalimumab trial. They also have ties to other pharmaceutical companies.
Dr. Langley has served as principal investigator for and is on the scientific advisory boards of Amgen, which sponsored the etanercept pediatric psoriasis study. He also has ties to other pharmaceutical companies.
COPENHAGEN – The longest-ever clinical trials of etanercept and adalimumab for pediatric psoriasis show reassuring maintenance of efficacy, coupled with safety and tolerability profiles similar to what has been seen in long-term trials in adults, investigators reported at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Richard G. Langley presented outcomes from a 5-year open-label extension of an initial 12-week, multicenter, double-blind, randomized trial of etanercept or placebo in children and adolescents with moderate to severe chronic plaque psoriasis. The primary results were published more than 7 years ago (N Engl J Med. 2008 Jan 17;358[3]:241-51).
“This is the largest and longest follow-up of any biologic in children and adolescents to date. I think it’s encouraging data and should be reassuring to those of us who are managing this important population of pediatric patients in our conversations with parents and families,”said Dr. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
In the original 211-patient study, 57% of patients receiving etanercept (Enbrel) once weekly at 0.8 mg/kg to a maximum of 50 mg achieved a PASI 75 response at week 12, and 27% had a PASI 90. In the 69 patients who completed the full 264 weeks of follow-up, those response rates remained essentially unchanged.
Dr. Langley was quick to point out that this was an as-observed analysis, meaning results were counted only in those patients still participating at week 264. While conceding that the two-thirds dropout rate is an important study limitation, he added: “Notwithstanding that, what matters to us in the clinic are the patients we continue to treat and how they’re responding.”
Of note, most study discontinuations didn’t result from loss of response or adverse events, they were due to withdrawal of consent by families in which the patient began the study as a cooperative child and who as time went by turned into an independent and often willful teenager, he said.
No new safety signals arose over the course of 5 years. There were no opportunistic infections, no malignancies. The most common adverse events were the same ones seen in the original short-term study: upper respiratory infections, nasopharyngitis, and headaches. There was only one serious adverse event deemed by investigators as ‘possibly related’ to etanercept therapy: a case of cellulitis.
Separately, Dr. Diamant Thaci and Dr. Kim A. Papp presented 52-week outcomes for different aspects of the pivotal phase III randomized trial which earlier in 2015 earned adalimumab (Humira) European Commission marketing approval as the first biologic agent indicated for treatment of children as young as age 4 years, as well as for adolescents. The multi-arm trial included 114 patients aged 4-17 years with moderate to severe plaque psoriasis.
Dr. Thaci reported on the 37 subjects initially randomized double-blind to 16 weeks of oral methotrexate at 0.1-0.4 mg/kg weekly. The 19 patients (51%) who were deemed nonresponders to methotrexate because of inadequate PASI response at week 16 were then switched to open-label adalimumab at 0.8 mg/kg every other week for the remainder of the 52 weeks.
After 16 weeks on adalimumab, the methotrexate nonresponders had a PASI 75 of 90% and a PASI 90 of 74%, and 79% of the subjects were rated clear or almost clear by Physician’s Global Assessment. At week 52, the PASI 75 rate was 79%, the PASI 90 rate was 58%, and 68% of patients were rated clear or almost clear, according to Dr. Thaci of University Hospital Schleswig-Holstein, in L<scaps>ü</scaps>beck, Germany.
The side effects of methotrexate and adalimumab were similar to those seen in adults. There were no serious adverse events. The infections that occurred during adalimumab therapy were “very banal things,” mostly nasopharyngitis and upper respiratory tract infections, the dermatologist said. There were no opportunistic infections, malignancies, or cases of tuberculosis during the phase III study.
This was an important analysis because it recapitulates daily clinical practice, he explained. In most of the world, when dermatologists deem it time for systemic therapy, they generally start out with methotrexate, reserving biologics for second-line therapy because of the cost.
Dr. Papp reported on 39 patients on adalimumab at 0.4 mg/kg every other week, and 38 on 0.8 mg/kg every other week throughout the 52-week study. The response rate was essentially a flat line from week 16 to week 52, with PASI 75s of 44% at week 16 and 50% at week 52 in the low-dose group, and 58% and 56% in the high-dose group. Half of patients on 0.4 mg/kg were clear or almost clear at week 52, as were 56% on 0.8 mg/kg.
There was a nonsignificant trend for an increasing infection rate with greater exposure to adalimumab, which will require evaluation during the ongoing follow-up beyond 52 weeks, said Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
“I think what’s gratifying about this is we see that these children actually have a robust response and that response is maintained over a full year of treatment, which is reassuring because that reflects what we’ve seen in the adult population as well,” he said.
Dr. Papp and Dr. Thaci receive research funding and serve as scientific advisers to AbbVie, which sponsored the adalimumab trial. They also have ties to other pharmaceutical companies.
Dr. Langley has served as principal investigator for and is on the scientific advisory boards of Amgen, which sponsored the etanercept pediatric psoriasis study. He also has ties to other pharmaceutical companies.
COPENHAGEN – The longest-ever clinical trials of etanercept and adalimumab for pediatric psoriasis show reassuring maintenance of efficacy, coupled with safety and tolerability profiles similar to what has been seen in long-term trials in adults, investigators reported at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Richard G. Langley presented outcomes from a 5-year open-label extension of an initial 12-week, multicenter, double-blind, randomized trial of etanercept or placebo in children and adolescents with moderate to severe chronic plaque psoriasis. The primary results were published more than 7 years ago (N Engl J Med. 2008 Jan 17;358[3]:241-51).
“This is the largest and longest follow-up of any biologic in children and adolescents to date. I think it’s encouraging data and should be reassuring to those of us who are managing this important population of pediatric patients in our conversations with parents and families,”said Dr. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
In the original 211-patient study, 57% of patients receiving etanercept (Enbrel) once weekly at 0.8 mg/kg to a maximum of 50 mg achieved a PASI 75 response at week 12, and 27% had a PASI 90. In the 69 patients who completed the full 264 weeks of follow-up, those response rates remained essentially unchanged.
Dr. Langley was quick to point out that this was an as-observed analysis, meaning results were counted only in those patients still participating at week 264. While conceding that the two-thirds dropout rate is an important study limitation, he added: “Notwithstanding that, what matters to us in the clinic are the patients we continue to treat and how they’re responding.”
Of note, most study discontinuations didn’t result from loss of response or adverse events, they were due to withdrawal of consent by families in which the patient began the study as a cooperative child and who as time went by turned into an independent and often willful teenager, he said.
No new safety signals arose over the course of 5 years. There were no opportunistic infections, no malignancies. The most common adverse events were the same ones seen in the original short-term study: upper respiratory infections, nasopharyngitis, and headaches. There was only one serious adverse event deemed by investigators as ‘possibly related’ to etanercept therapy: a case of cellulitis.
Separately, Dr. Diamant Thaci and Dr. Kim A. Papp presented 52-week outcomes for different aspects of the pivotal phase III randomized trial which earlier in 2015 earned adalimumab (Humira) European Commission marketing approval as the first biologic agent indicated for treatment of children as young as age 4 years, as well as for adolescents. The multi-arm trial included 114 patients aged 4-17 years with moderate to severe plaque psoriasis.
Dr. Thaci reported on the 37 subjects initially randomized double-blind to 16 weeks of oral methotrexate at 0.1-0.4 mg/kg weekly. The 19 patients (51%) who were deemed nonresponders to methotrexate because of inadequate PASI response at week 16 were then switched to open-label adalimumab at 0.8 mg/kg every other week for the remainder of the 52 weeks.
After 16 weeks on adalimumab, the methotrexate nonresponders had a PASI 75 of 90% and a PASI 90 of 74%, and 79% of the subjects were rated clear or almost clear by Physician’s Global Assessment. At week 52, the PASI 75 rate was 79%, the PASI 90 rate was 58%, and 68% of patients were rated clear or almost clear, according to Dr. Thaci of University Hospital Schleswig-Holstein, in L<scaps>ü</scaps>beck, Germany.
The side effects of methotrexate and adalimumab were similar to those seen in adults. There were no serious adverse events. The infections that occurred during adalimumab therapy were “very banal things,” mostly nasopharyngitis and upper respiratory tract infections, the dermatologist said. There were no opportunistic infections, malignancies, or cases of tuberculosis during the phase III study.
This was an important analysis because it recapitulates daily clinical practice, he explained. In most of the world, when dermatologists deem it time for systemic therapy, they generally start out with methotrexate, reserving biologics for second-line therapy because of the cost.
Dr. Papp reported on 39 patients on adalimumab at 0.4 mg/kg every other week, and 38 on 0.8 mg/kg every other week throughout the 52-week study. The response rate was essentially a flat line from week 16 to week 52, with PASI 75s of 44% at week 16 and 50% at week 52 in the low-dose group, and 58% and 56% in the high-dose group. Half of patients on 0.4 mg/kg were clear or almost clear at week 52, as were 56% on 0.8 mg/kg.
There was a nonsignificant trend for an increasing infection rate with greater exposure to adalimumab, which will require evaluation during the ongoing follow-up beyond 52 weeks, said Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
“I think what’s gratifying about this is we see that these children actually have a robust response and that response is maintained over a full year of treatment, which is reassuring because that reflects what we’ve seen in the adult population as well,” he said.
Dr. Papp and Dr. Thaci receive research funding and serve as scientific advisers to AbbVie, which sponsored the adalimumab trial. They also have ties to other pharmaceutical companies.
Dr. Langley has served as principal investigator for and is on the scientific advisory boards of Amgen, which sponsored the etanercept pediatric psoriasis study. He also has ties to other pharmaceutical companies.
EXPERT ANALYSIS FROM THE EADV CONGRESS
EADV: Pediatric psoriasis called ‘grossly undertreated’
COPENHAGEN – Children and adolescents with moderate to severe psoriasis are generally undertreated, with resultant potential psychological impairment, social stigmatization, and isolation, psoriasis experts agreed at the annual congress of the European Academy of Dermatology and Venereology.
In a session featuring new long-term safety and efficacy data from extended pediatric clinical trials of etanercept and adalimumab, prominent clinical trial investigators who presented the findings asserted that many physicians and parents are overly timid about the use of systemic treatment options in children and adolescents when such therapy is clearly warranted.
“The burden of psoriasis is particularly acute in the pediatric population. I always ask patients, ‘How is psoriasis affecting you?’ And with children, it’s affecting them and it’s also affecting their parents. If it’s affecting their self-esteem – if it’s ruining your life and you can’t control it with topical agents – I think it’s time to think of other things,” declared Dr. Richard G. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
Yet all too often that doesn’t happen, as documented in the recently reported physician portion of the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, which included 391 dermatologists and 390 rheumatologists in North America and Western Europe (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:2002-10).
Dr. Langley was a coinvestigator in MAPP, which found that 39% of dermatologists reported treating their moderate to severe psoriasis patients with conventional oral and/or biologic agents (19.5% and 19.6%, respectively). A total of 75% indicated they prescribe topical medications as monotherapy for their patients with moderate to severe psoriasis. In children, that rate was even higher, he said, despite the fact that topical monotherapy is clearly inadequate for treatment of more severe disease.
“I think there’s a fear about using systemics among parents and among some practitioners, which was one of the top reasons in the MAPP survey that people didn’t get appropriate treatment,” he said.
That’s a shortsighted attitude, the dermatologist continued: “The risk is not just the risk of the drug, but the risk of untreated disease, because untreated disease devastates patients.”
MAPP was the largest-ever survey of physician and patient perspectives regarding psoriasis and psoriatic arthritis. The patient perspective, derived from interviews with nearly 3,500 patients, was published earlier (J Am Acad Dermatol. 2014 May;70[5]:871-81).
One impediment to more widespread use of systemic therapies for pediatric psoriasis is that it’s almost entirely off-label prescribing. In the United States, no conventional oral agents or biologics are Food and Drug Administration approved for use in psoriasis patients under age 18 years. That was the case in Europe as well until earlier this year, when adalimumab (Humira) received European marketing approval for children ages 4 years and up with severe chronic plaque psoriasis with an inadequate response to topical agents and phototherapy or in whom such therapies are contraindicated.
Dr. Kim A. Papp, who presented new 52-week safety and efficacy data from a phase III study of adalimumab in pediatric psoriasis patients, said that even when dermatologists utilize biologics in pediatric patients, the medications are typically underdosed. In the phase III pediatric adalimumab trial, for example, most participants were overweight or obese, and efficacy dropped off with increasing body mass index, as has been the case in trials of most of the biologics.
“When I look at the doses of the biologic agents that are used in treating the pediatric population and what we know about how these molecules are distributed in the body, we can safely say we are grossly underdosing children. We’re doing that because we believe somehow they’re at greater risk from exposures that are comparable to those in the adult population. And it’s not true. What we’ve seen over 20 years of using the biologics is that these agents are very safe and very effective when used appropriately in adequate doses,” according to Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
Asked which biologics he’s most comfortable with in prescribing for pediatric patients, Dr. Papp replied, “I think the best biologic therapies for pediatric patients are the ones that have been studied in the pediatric population: etanercept, ustekinumab, and adalimumab. Those three are the ones we want to choose because we at least have some guidance and some assurance in terms of expectations of response and adverse events.”
Dr. Papp and Dr. Langley have served as principal investigators of numerous clinical trials for and served as advisors to pharmaceutical companies developing dermatologic medications.
COPENHAGEN – Children and adolescents with moderate to severe psoriasis are generally undertreated, with resultant potential psychological impairment, social stigmatization, and isolation, psoriasis experts agreed at the annual congress of the European Academy of Dermatology and Venereology.
In a session featuring new long-term safety and efficacy data from extended pediatric clinical trials of etanercept and adalimumab, prominent clinical trial investigators who presented the findings asserted that many physicians and parents are overly timid about the use of systemic treatment options in children and adolescents when such therapy is clearly warranted.
“The burden of psoriasis is particularly acute in the pediatric population. I always ask patients, ‘How is psoriasis affecting you?’ And with children, it’s affecting them and it’s also affecting their parents. If it’s affecting their self-esteem – if it’s ruining your life and you can’t control it with topical agents – I think it’s time to think of other things,” declared Dr. Richard G. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
Yet all too often that doesn’t happen, as documented in the recently reported physician portion of the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, which included 391 dermatologists and 390 rheumatologists in North America and Western Europe (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:2002-10).
Dr. Langley was a coinvestigator in MAPP, which found that 39% of dermatologists reported treating their moderate to severe psoriasis patients with conventional oral and/or biologic agents (19.5% and 19.6%, respectively). A total of 75% indicated they prescribe topical medications as monotherapy for their patients with moderate to severe psoriasis. In children, that rate was even higher, he said, despite the fact that topical monotherapy is clearly inadequate for treatment of more severe disease.
“I think there’s a fear about using systemics among parents and among some practitioners, which was one of the top reasons in the MAPP survey that people didn’t get appropriate treatment,” he said.
That’s a shortsighted attitude, the dermatologist continued: “The risk is not just the risk of the drug, but the risk of untreated disease, because untreated disease devastates patients.”
MAPP was the largest-ever survey of physician and patient perspectives regarding psoriasis and psoriatic arthritis. The patient perspective, derived from interviews with nearly 3,500 patients, was published earlier (J Am Acad Dermatol. 2014 May;70[5]:871-81).
One impediment to more widespread use of systemic therapies for pediatric psoriasis is that it’s almost entirely off-label prescribing. In the United States, no conventional oral agents or biologics are Food and Drug Administration approved for use in psoriasis patients under age 18 years. That was the case in Europe as well until earlier this year, when adalimumab (Humira) received European marketing approval for children ages 4 years and up with severe chronic plaque psoriasis with an inadequate response to topical agents and phototherapy or in whom such therapies are contraindicated.
Dr. Kim A. Papp, who presented new 52-week safety and efficacy data from a phase III study of adalimumab in pediatric psoriasis patients, said that even when dermatologists utilize biologics in pediatric patients, the medications are typically underdosed. In the phase III pediatric adalimumab trial, for example, most participants were overweight or obese, and efficacy dropped off with increasing body mass index, as has been the case in trials of most of the biologics.
“When I look at the doses of the biologic agents that are used in treating the pediatric population and what we know about how these molecules are distributed in the body, we can safely say we are grossly underdosing children. We’re doing that because we believe somehow they’re at greater risk from exposures that are comparable to those in the adult population. And it’s not true. What we’ve seen over 20 years of using the biologics is that these agents are very safe and very effective when used appropriately in adequate doses,” according to Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
Asked which biologics he’s most comfortable with in prescribing for pediatric patients, Dr. Papp replied, “I think the best biologic therapies for pediatric patients are the ones that have been studied in the pediatric population: etanercept, ustekinumab, and adalimumab. Those three are the ones we want to choose because we at least have some guidance and some assurance in terms of expectations of response and adverse events.”
Dr. Papp and Dr. Langley have served as principal investigators of numerous clinical trials for and served as advisors to pharmaceutical companies developing dermatologic medications.
COPENHAGEN – Children and adolescents with moderate to severe psoriasis are generally undertreated, with resultant potential psychological impairment, social stigmatization, and isolation, psoriasis experts agreed at the annual congress of the European Academy of Dermatology and Venereology.
In a session featuring new long-term safety and efficacy data from extended pediatric clinical trials of etanercept and adalimumab, prominent clinical trial investigators who presented the findings asserted that many physicians and parents are overly timid about the use of systemic treatment options in children and adolescents when such therapy is clearly warranted.
“The burden of psoriasis is particularly acute in the pediatric population. I always ask patients, ‘How is psoriasis affecting you?’ And with children, it’s affecting them and it’s also affecting their parents. If it’s affecting their self-esteem – if it’s ruining your life and you can’t control it with topical agents – I think it’s time to think of other things,” declared Dr. Richard G. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
Yet all too often that doesn’t happen, as documented in the recently reported physician portion of the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, which included 391 dermatologists and 390 rheumatologists in North America and Western Europe (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:2002-10).
Dr. Langley was a coinvestigator in MAPP, which found that 39% of dermatologists reported treating their moderate to severe psoriasis patients with conventional oral and/or biologic agents (19.5% and 19.6%, respectively). A total of 75% indicated they prescribe topical medications as monotherapy for their patients with moderate to severe psoriasis. In children, that rate was even higher, he said, despite the fact that topical monotherapy is clearly inadequate for treatment of more severe disease.
“I think there’s a fear about using systemics among parents and among some practitioners, which was one of the top reasons in the MAPP survey that people didn’t get appropriate treatment,” he said.
That’s a shortsighted attitude, the dermatologist continued: “The risk is not just the risk of the drug, but the risk of untreated disease, because untreated disease devastates patients.”
MAPP was the largest-ever survey of physician and patient perspectives regarding psoriasis and psoriatic arthritis. The patient perspective, derived from interviews with nearly 3,500 patients, was published earlier (J Am Acad Dermatol. 2014 May;70[5]:871-81).
One impediment to more widespread use of systemic therapies for pediatric psoriasis is that it’s almost entirely off-label prescribing. In the United States, no conventional oral agents or biologics are Food and Drug Administration approved for use in psoriasis patients under age 18 years. That was the case in Europe as well until earlier this year, when adalimumab (Humira) received European marketing approval for children ages 4 years and up with severe chronic plaque psoriasis with an inadequate response to topical agents and phototherapy or in whom such therapies are contraindicated.
Dr. Kim A. Papp, who presented new 52-week safety and efficacy data from a phase III study of adalimumab in pediatric psoriasis patients, said that even when dermatologists utilize biologics in pediatric patients, the medications are typically underdosed. In the phase III pediatric adalimumab trial, for example, most participants were overweight or obese, and efficacy dropped off with increasing body mass index, as has been the case in trials of most of the biologics.
“When I look at the doses of the biologic agents that are used in treating the pediatric population and what we know about how these molecules are distributed in the body, we can safely say we are grossly underdosing children. We’re doing that because we believe somehow they’re at greater risk from exposures that are comparable to those in the adult population. And it’s not true. What we’ve seen over 20 years of using the biologics is that these agents are very safe and very effective when used appropriately in adequate doses,” according to Dr. Papp, president of Probity Medical Research in Waterloo, Ont.
Asked which biologics he’s most comfortable with in prescribing for pediatric patients, Dr. Papp replied, “I think the best biologic therapies for pediatric patients are the ones that have been studied in the pediatric population: etanercept, ustekinumab, and adalimumab. Those three are the ones we want to choose because we at least have some guidance and some assurance in terms of expectations of response and adverse events.”
Dr. Papp and Dr. Langley have served as principal investigators of numerous clinical trials for and served as advisors to pharmaceutical companies developing dermatologic medications.
EXPERT ANALYSIS FROM THE EADV CONGRESS
ACR: Cardiovascular risk factors in psoriatic diseases are common, often go untreated
SAN FRANCISCO – Despite their frequent contact with the health care system, patients with psoriasis and psoriatic arthritis often receive no treatment for major cardiovascular risk factors, according to two large multicenter studies.
“We identified a gap in quality of care in terms of the primary prevention of cardiovascular risk factors in psoriatic arthritis and psoriasis. The next step will be to develop strategies to increase awareness and implement treatment recommendations among primary care physicians, dermatologists, and rheumatologists,” Dr. Lihi Eder of the University of Toronto said in an interview at the annual meeting of the American College of Rheumatology.
Psoriatic and cardiovascular diseases share an inflammatory etiology and often co-occur. In past studies, patients with psoriasis and psoriatic arthritis were about 50% more likely than average to have dyslipidemia and ischemic heart disease, and about 80%-90% more likely than usual to have hypertension and diabetes, Dr. Eder said.
She and her associates studied dyslipidemia and hypertension among 1,327 patients with psoriatic arthritis and 927 patients with psoriasis at eight sites in Canada, the United States, and Israel as part of the International Psoriasis & Arthritis Research Team (IPART). Based on medical and laboratory reports and self-reported data, the investigators assessed these comorbidities and whether treatment adhered to cholesterol and hypertension guidelines from the American College of Cardiology and the American Heart Association (Circulation. 2014 Jul 1;129:S1-45), and the Eighth Joint National Committee (JAMA. 2014 Feb 5;311[5]:507-20), respectively.
More than 80% of patients in the cohort had at least one modifiable cardiovascular risk factor, Dr. Eder said. While 6% had ischemic heart disease, 45% had hypertension, 71% had dyslipidemia, 13% had diabetes, 54% had central obesity, and 17% were current smokers. Furthermore, close to half of patients who had been diagnosed with hypertension had uncontrolled high blood pressure, and 57% were not receiving antihypertensive medications. Likewise, 58% of patients with dyslipidemia met criteria for statins, but only a third of these patients were receiving them.
Undertreatment was associated with having psoriatic arthritis or severe psoriasis and with having a high school or lower level of education, Dr. Eder added. “You have to remember that this study was conducted among specialists – these are supposed to be experts in the field,” she said. “If the treatment adherence is relatively low in these centers, then I would expect that for patients who are being followed in centers that do not specialize in psoriatic disease, adherence would be even lower.”
The second study detected significantly higher rates of cardiovascular risk factors among patients with psoriatic diseases, compared with controls from the Health Improvement Network, a medical records database that covers more than 9 million individuals in the United Kingdom. Patients with psoriatic arthritis or severe psoriasis were significantly more likely than were controls to develop hypertension, hyperlipidemia, obesity, or diabetes, with odds ratios ranging from 1.22 to 1.78, reported Dr. Kashif A. Jafri, who led the study while he was an internal medicine resident at the University of Pennsylvania in Philadelphia.
But despite their disproportionate risk, patients were treated at about the same rate as controls, Dr. Jafri said. About 15% of individuals with hypertension received no treatment, 30%-40% with hyperlipidemia went untreated, and nearly 60% with diabetes received no documented therapy. “The absence of a significant difference in receipt of appropriate therapy among the groups reflects a need for more careful attention to the management of cardiovascular risk factors in patients with inflammatory diseases,” Dr. Jafri emphasized. Because these risk factors can be successfully treated, it is “critical” to educate primary care providers about the need to do so, he said.
Rheumatologists also should periodically discuss cardiovascular risk factors with their patients as part of routine care, Dr. Jafri advised. “Although there are obviously time constraints during each office visit, this is a topic that dramatically influences the morbidity and mortality of our patient population, and rheumatologists have the unique ability to address this issue in the context of their long-term relationships with their patients,” he said.
Dr. Jafri is now a fellow in rheumatology at the University of California, San Francisco. His was supported by an Ephraim P. Engleman Endowed Resident Research Preceptorship Award from the Rheumatology Research Foundation. IPART is sponsored by the Krembil Foundation and the Canadian Institutes of Health Research. Dr. Jafri and Dr. Eder had no disclosures.
SAN FRANCISCO – Despite their frequent contact with the health care system, patients with psoriasis and psoriatic arthritis often receive no treatment for major cardiovascular risk factors, according to two large multicenter studies.
“We identified a gap in quality of care in terms of the primary prevention of cardiovascular risk factors in psoriatic arthritis and psoriasis. The next step will be to develop strategies to increase awareness and implement treatment recommendations among primary care physicians, dermatologists, and rheumatologists,” Dr. Lihi Eder of the University of Toronto said in an interview at the annual meeting of the American College of Rheumatology.
Psoriatic and cardiovascular diseases share an inflammatory etiology and often co-occur. In past studies, patients with psoriasis and psoriatic arthritis were about 50% more likely than average to have dyslipidemia and ischemic heart disease, and about 80%-90% more likely than usual to have hypertension and diabetes, Dr. Eder said.
She and her associates studied dyslipidemia and hypertension among 1,327 patients with psoriatic arthritis and 927 patients with psoriasis at eight sites in Canada, the United States, and Israel as part of the International Psoriasis & Arthritis Research Team (IPART). Based on medical and laboratory reports and self-reported data, the investigators assessed these comorbidities and whether treatment adhered to cholesterol and hypertension guidelines from the American College of Cardiology and the American Heart Association (Circulation. 2014 Jul 1;129:S1-45), and the Eighth Joint National Committee (JAMA. 2014 Feb 5;311[5]:507-20), respectively.
More than 80% of patients in the cohort had at least one modifiable cardiovascular risk factor, Dr. Eder said. While 6% had ischemic heart disease, 45% had hypertension, 71% had dyslipidemia, 13% had diabetes, 54% had central obesity, and 17% were current smokers. Furthermore, close to half of patients who had been diagnosed with hypertension had uncontrolled high blood pressure, and 57% were not receiving antihypertensive medications. Likewise, 58% of patients with dyslipidemia met criteria for statins, but only a third of these patients were receiving them.
Undertreatment was associated with having psoriatic arthritis or severe psoriasis and with having a high school or lower level of education, Dr. Eder added. “You have to remember that this study was conducted among specialists – these are supposed to be experts in the field,” she said. “If the treatment adherence is relatively low in these centers, then I would expect that for patients who are being followed in centers that do not specialize in psoriatic disease, adherence would be even lower.”
The second study detected significantly higher rates of cardiovascular risk factors among patients with psoriatic diseases, compared with controls from the Health Improvement Network, a medical records database that covers more than 9 million individuals in the United Kingdom. Patients with psoriatic arthritis or severe psoriasis were significantly more likely than were controls to develop hypertension, hyperlipidemia, obesity, or diabetes, with odds ratios ranging from 1.22 to 1.78, reported Dr. Kashif A. Jafri, who led the study while he was an internal medicine resident at the University of Pennsylvania in Philadelphia.
But despite their disproportionate risk, patients were treated at about the same rate as controls, Dr. Jafri said. About 15% of individuals with hypertension received no treatment, 30%-40% with hyperlipidemia went untreated, and nearly 60% with diabetes received no documented therapy. “The absence of a significant difference in receipt of appropriate therapy among the groups reflects a need for more careful attention to the management of cardiovascular risk factors in patients with inflammatory diseases,” Dr. Jafri emphasized. Because these risk factors can be successfully treated, it is “critical” to educate primary care providers about the need to do so, he said.
Rheumatologists also should periodically discuss cardiovascular risk factors with their patients as part of routine care, Dr. Jafri advised. “Although there are obviously time constraints during each office visit, this is a topic that dramatically influences the morbidity and mortality of our patient population, and rheumatologists have the unique ability to address this issue in the context of their long-term relationships with their patients,” he said.
Dr. Jafri is now a fellow in rheumatology at the University of California, San Francisco. His was supported by an Ephraim P. Engleman Endowed Resident Research Preceptorship Award from the Rheumatology Research Foundation. IPART is sponsored by the Krembil Foundation and the Canadian Institutes of Health Research. Dr. Jafri and Dr. Eder had no disclosures.
SAN FRANCISCO – Despite their frequent contact with the health care system, patients with psoriasis and psoriatic arthritis often receive no treatment for major cardiovascular risk factors, according to two large multicenter studies.
“We identified a gap in quality of care in terms of the primary prevention of cardiovascular risk factors in psoriatic arthritis and psoriasis. The next step will be to develop strategies to increase awareness and implement treatment recommendations among primary care physicians, dermatologists, and rheumatologists,” Dr. Lihi Eder of the University of Toronto said in an interview at the annual meeting of the American College of Rheumatology.
Psoriatic and cardiovascular diseases share an inflammatory etiology and often co-occur. In past studies, patients with psoriasis and psoriatic arthritis were about 50% more likely than average to have dyslipidemia and ischemic heart disease, and about 80%-90% more likely than usual to have hypertension and diabetes, Dr. Eder said.
She and her associates studied dyslipidemia and hypertension among 1,327 patients with psoriatic arthritis and 927 patients with psoriasis at eight sites in Canada, the United States, and Israel as part of the International Psoriasis & Arthritis Research Team (IPART). Based on medical and laboratory reports and self-reported data, the investigators assessed these comorbidities and whether treatment adhered to cholesterol and hypertension guidelines from the American College of Cardiology and the American Heart Association (Circulation. 2014 Jul 1;129:S1-45), and the Eighth Joint National Committee (JAMA. 2014 Feb 5;311[5]:507-20), respectively.
More than 80% of patients in the cohort had at least one modifiable cardiovascular risk factor, Dr. Eder said. While 6% had ischemic heart disease, 45% had hypertension, 71% had dyslipidemia, 13% had diabetes, 54% had central obesity, and 17% were current smokers. Furthermore, close to half of patients who had been diagnosed with hypertension had uncontrolled high blood pressure, and 57% were not receiving antihypertensive medications. Likewise, 58% of patients with dyslipidemia met criteria for statins, but only a third of these patients were receiving them.
Undertreatment was associated with having psoriatic arthritis or severe psoriasis and with having a high school or lower level of education, Dr. Eder added. “You have to remember that this study was conducted among specialists – these are supposed to be experts in the field,” she said. “If the treatment adherence is relatively low in these centers, then I would expect that for patients who are being followed in centers that do not specialize in psoriatic disease, adherence would be even lower.”
The second study detected significantly higher rates of cardiovascular risk factors among patients with psoriatic diseases, compared with controls from the Health Improvement Network, a medical records database that covers more than 9 million individuals in the United Kingdom. Patients with psoriatic arthritis or severe psoriasis were significantly more likely than were controls to develop hypertension, hyperlipidemia, obesity, or diabetes, with odds ratios ranging from 1.22 to 1.78, reported Dr. Kashif A. Jafri, who led the study while he was an internal medicine resident at the University of Pennsylvania in Philadelphia.
But despite their disproportionate risk, patients were treated at about the same rate as controls, Dr. Jafri said. About 15% of individuals with hypertension received no treatment, 30%-40% with hyperlipidemia went untreated, and nearly 60% with diabetes received no documented therapy. “The absence of a significant difference in receipt of appropriate therapy among the groups reflects a need for more careful attention to the management of cardiovascular risk factors in patients with inflammatory diseases,” Dr. Jafri emphasized. Because these risk factors can be successfully treated, it is “critical” to educate primary care providers about the need to do so, he said.
Rheumatologists also should periodically discuss cardiovascular risk factors with their patients as part of routine care, Dr. Jafri advised. “Although there are obviously time constraints during each office visit, this is a topic that dramatically influences the morbidity and mortality of our patient population, and rheumatologists have the unique ability to address this issue in the context of their long-term relationships with their patients,” he said.
Dr. Jafri is now a fellow in rheumatology at the University of California, San Francisco. His was supported by an Ephraim P. Engleman Endowed Resident Research Preceptorship Award from the Rheumatology Research Foundation. IPART is sponsored by the Krembil Foundation and the Canadian Institutes of Health Research. Dr. Jafri and Dr. Eder had no disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point: Patients with psoriatic diseases have high rates of modifiable cardiovascular risk factors that often go untreated, based on two large studies.
Major finding: These risk factors were untreated about one-third to one-half of the time.
Data source: The first study included 1,327 patients with psoriatic arthritis and 927 patients with psoriasis identified through the International Psoriasis & Arthritis Research Team (IPART). The second study analyzed data from The Health Improvement Network, including 211,832 patients with psoriatic disease and more than 1.3 million controls.
Disclosures: The IPART is sponsored by the Krembil Foundation and the Canadian Institutes of Health Research. The second study was supported by an Ephraim P. Engleman Endowed Resident Research Preceptorship Award from the Rheumatology Research Foundation. Dr. Eder and Dr. Jafri had no disclosures.
State laws, regulatory concerns complicate biosimilars landscape
SAN FRANCISCO – A growing number of states are passing laws that set the parameters for how originator biologics may be replaced with biosimilars, and not all of them are helpful to physicians trying to maintain some knowledge and control over how prescriptions for biologics are dispensed, according to speakers at the annual meeting of the American College of Rheumatology.
These laws – now passed by a total of 19 states and Puerto Rico, including 12 in 2015 – address a requirement built into the Biologics Price Competition and Innovation Act of 2009 (part of the Affordable Care Act) that introduced the term “interchangeability” into the biosimilars approval pathway, stating that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” The law also gives 1 year of exclusive marketing rights to the first biosimilar approved as being interchangeable with the reference product.
Although regulations on how the Food and Drug Administration will deem a biosimilar to be interchangeable have yet to be drafted, it’s important for physicians to play an active role in shaping the laws that address interchangeability, said Dr. J. Eugene Huffstutter, a rheumatologist in private practice in Hixson, Tenn., and clinical assistant professor of medicine at the University of Tennessee, Chattanooga.
Dr. Huffstutter encouraged rheumatologists and other physicians to work with their local state medical associations to contact their state legislators to explain to them the need for strict laws on how biosimilars can be dispensed. He suggested that good state legislation on biosimilars should contain provisions stating that:
• Only FDA-approved interchangeable biosimilars can be substituted.
• No substitution can be made with “dispense as written” prescription.
• The prescribing physician must be notified of substitution within 1-5 days by electronic record or fax.
• The pharmacy must maintain a record of the dispensed drug.
Organizations including the ACR, the Coalition of State Rheumatology Organizations, patient groups, electronic prescribers, state medical societies, and pharmaceutical companies (for the most part) support strong state laws on biosimilars, while the pharmacy lobby and insurance companies have opposed them, Dr. Huffstutter said.
The 19 states with biosimilars laws include California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Massachusetts, New Jersey, North Carolina, North Dakota, Oregon, Tennessee, Texas, Utah, Virginia, and Washington, along with Puerto Rico. However, the laws in Oregon and Virginia will sunset in 2016. Another seven states have 2015 or current session legislation on biosimilar substitution: Hawaii, Maryland, Michigan, Mississippi, Oklahoma, Pennsylvania, and Vermont. States with bills that failed or were not acted upon at adjournment include Arizona, Arkansas, Nevada, and Rhode Island, according to information provided to Dr. Huffstutter by the Coalition.
State laws may differ on substitution notification, he noted. In Tennessee, the law (H.B. 572) states that notification should occur in “a reasonable period of time” instead of a defined period. “What may be reasonable for one person may not be reasonable for another. I really think 5 days is the outside time, or 5 business days, because if you’re thinking about some of the biosimilars that are coming down the pike, they’ll be given on a weekly basis, so you’ll at least know before [patients] get their second shot what they’re receiving,” Dr. Huffstutter noted.
Idaho is unique in that it impaneled a board of pharmacy regulation on biosimilar substitution rather than a separate law. It states that “A pharmacist may substitute an interchangeable biosimilar product for a prescribed biological product if the biosimilar has been determined by the FDA to be interchangeable and published in the Purple Book; the prescriber does not indicate by any means that the prescribed biological product must be dispensed; and the name of the drug and the manufacturer or the NDC [National Drug Code] number is documented in the patient medical record.”
The situation may become trickier as more biosimilars are approved, noted Dr. Huffstutter, who is a member of the ACR’s Government Affairs Committee and is a liaison to the Committee on Rheumatologic Care. It could potentially be a problem when a patient is taking a biosimilar for a particular originator biologic and then other biosimilars for that originator join the marketplace. A patient could potentially be switched from one biosimilar to another when a prescription is filled if the company marketing the second biosimilar happens to win a competitive bid with an insurance company, he said.
The filgrastim biosimilar called Zarxio is the only biosimilar currently approved in the United States, but the FDA has received two applications for biosimilars for inflammatory diseases: one from Celltrion for infliximab biosimilar Remsima (August 2014) and one from Sandoz for an etanercept biosimilar (October 2015). In addition to two infliximab biosimilars that have been approved in other countries, one etanercept biosimilar that has been approved in South Korea, and one adalimumab biosimilar approved in India, there are many others in development to treat inflammatory diseases as of July 2015, including 12 for adalimumab, 9 for etanercept, 5 for infliximab, 2 for tocilizumab, and 7 for rituximab, according to Dr. Jonathan Kay, professor of medicine and director of clinical research in the division of rheumatology at the University of Massachusetts, Worcester.
Unresolved regulatory concerns
In separate presentations at the meeting, Dr. Kay described many of the nuances that define biosimilars, which go by different terminology in other countries, such as “follow-on biologic” in Japan, “subsequent-entry biological” in Canada, and “similar biological medicinal product” in the European Union. They are defined as a legitimate copy of an off-patent biopharmaceutical that has undergone rigorous analytical comparison and clinical assessment, in comparison to its reference product, and are approved by a regulatory agency according to a specific pathway for biosimilar evaluation. These differ from biomimetics, which are developed as a replica of a biopharmaceutical but have not been developed, assessed, or approved according to regulatory guidelines for biosimilars.
The FDA takes a “totality of the evidence” approach to establish biosimilarity. The biosimilar pathway for approval is different from the originator pathway by relying more on analytical and preclinical studies and less on the clinical pharmacology and clinical trial data to support biosimilarity.
However, the agency has not yet published final guidance for all steps in demonstrating biosimilarity, particularly for clinical pharmacology data. Draft guidance says the biosimilar must be analyzed and assigned to an assessment grade: not similar, similar, highly similar, and highly similar with fingerprintlike similarity.
During production, both originator and biosimilar biopharmaceuticals can have protein-folding variants, misfolding, aggregation, enzymatic cleavage, and degradation that can lead to inactivation of the protein or increased immunogenicity. Even so, most biosimilars are not identical to the originator because of post-translational modifications, but they do not matter as long as they are not clinically meaningful. Even originator products can drift over time because small changes in manufacturing processes can lead to gradual changes in the molecule, Dr. Kay said.
Extrapolation of indications from the originator to a biosimilar is another area of concern, Dr. Kay said. The FDA will consider the extrapolation of data from a clinical trial of a biosimilar conducted in one disease to support approval for additional indications for which the originator product is already licensed, but not across indications with different mechanisms of action, such as between rheumatoid arthritis and non-Hodgkin’s lymphoma for rituximab. But for which inflammatory diseases should a biosimilar be studied to provide adequate information for extrapolation of indications? Dr. Kay asked. This situation brings about questions of whether dermatologists would be comfortable using a biosimilar that has been studied for rheumatoid arthritis to treat psoriasis or gastroenterologists using a drug with data only from psoriatic arthritis to treat Crohn’s disease or ulcerative colitis.
Both the Coalition of State Rheumatology Organizations and the ACR oppose extrapolation of indications from the clinical trial data of a biosimilar in one disease to support approval of additional indications for which the originator product is already licensed, but Dr. Kay thought that “extrapolation of indications makes perfect sense” because it won’t be possible to review a biosimilar for indications not already approved for the originator and it’s natural to extrapolate to already approved indications once the protein is shown to function nearly identically to the originator.
Ideally, the nomenclature system for biosimilars should clearly identify each product to improve pharmacovigilance and to differentiate between products that have not been determined to be interchangeable, Dr. Kay said. In August, the FDA announced draft guidance proposing that all biopharmaceutical products (originator and biosimilars) would have a nonproprietary name that includes a suffix of four lowercase letters that is devoid of meaning. For example, all products that share a core name such as replicamab would be named replicamab-cznm, replicamab-hixf, and so on, Dr. Kay said. Some people have voiced concern that it would be better for names to have some meaning, such as using an abbreviated name for the developing company along with the nonproprietary name of the originator product, but others noted that method could be problematic when companies merge or are acquired by others.
Dr. Huffstutter disclosed relationships with Janssen, UCB, Lilly, Pfizer, Genentech, Bristol-Myers Squibb, and Celgene. Dr. Kay has received grant and research support from many pharmaceutical companies and has served as a consultant or on an advisory board for many pharmaceutical companies, including those developing biosimilars.
SAN FRANCISCO – A growing number of states are passing laws that set the parameters for how originator biologics may be replaced with biosimilars, and not all of them are helpful to physicians trying to maintain some knowledge and control over how prescriptions for biologics are dispensed, according to speakers at the annual meeting of the American College of Rheumatology.
These laws – now passed by a total of 19 states and Puerto Rico, including 12 in 2015 – address a requirement built into the Biologics Price Competition and Innovation Act of 2009 (part of the Affordable Care Act) that introduced the term “interchangeability” into the biosimilars approval pathway, stating that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” The law also gives 1 year of exclusive marketing rights to the first biosimilar approved as being interchangeable with the reference product.
Although regulations on how the Food and Drug Administration will deem a biosimilar to be interchangeable have yet to be drafted, it’s important for physicians to play an active role in shaping the laws that address interchangeability, said Dr. J. Eugene Huffstutter, a rheumatologist in private practice in Hixson, Tenn., and clinical assistant professor of medicine at the University of Tennessee, Chattanooga.
Dr. Huffstutter encouraged rheumatologists and other physicians to work with their local state medical associations to contact their state legislators to explain to them the need for strict laws on how biosimilars can be dispensed. He suggested that good state legislation on biosimilars should contain provisions stating that:
• Only FDA-approved interchangeable biosimilars can be substituted.
• No substitution can be made with “dispense as written” prescription.
• The prescribing physician must be notified of substitution within 1-5 days by electronic record or fax.
• The pharmacy must maintain a record of the dispensed drug.
Organizations including the ACR, the Coalition of State Rheumatology Organizations, patient groups, electronic prescribers, state medical societies, and pharmaceutical companies (for the most part) support strong state laws on biosimilars, while the pharmacy lobby and insurance companies have opposed them, Dr. Huffstutter said.
The 19 states with biosimilars laws include California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Massachusetts, New Jersey, North Carolina, North Dakota, Oregon, Tennessee, Texas, Utah, Virginia, and Washington, along with Puerto Rico. However, the laws in Oregon and Virginia will sunset in 2016. Another seven states have 2015 or current session legislation on biosimilar substitution: Hawaii, Maryland, Michigan, Mississippi, Oklahoma, Pennsylvania, and Vermont. States with bills that failed or were not acted upon at adjournment include Arizona, Arkansas, Nevada, and Rhode Island, according to information provided to Dr. Huffstutter by the Coalition.
State laws may differ on substitution notification, he noted. In Tennessee, the law (H.B. 572) states that notification should occur in “a reasonable period of time” instead of a defined period. “What may be reasonable for one person may not be reasonable for another. I really think 5 days is the outside time, or 5 business days, because if you’re thinking about some of the biosimilars that are coming down the pike, they’ll be given on a weekly basis, so you’ll at least know before [patients] get their second shot what they’re receiving,” Dr. Huffstutter noted.
Idaho is unique in that it impaneled a board of pharmacy regulation on biosimilar substitution rather than a separate law. It states that “A pharmacist may substitute an interchangeable biosimilar product for a prescribed biological product if the biosimilar has been determined by the FDA to be interchangeable and published in the Purple Book; the prescriber does not indicate by any means that the prescribed biological product must be dispensed; and the name of the drug and the manufacturer or the NDC [National Drug Code] number is documented in the patient medical record.”
The situation may become trickier as more biosimilars are approved, noted Dr. Huffstutter, who is a member of the ACR’s Government Affairs Committee and is a liaison to the Committee on Rheumatologic Care. It could potentially be a problem when a patient is taking a biosimilar for a particular originator biologic and then other biosimilars for that originator join the marketplace. A patient could potentially be switched from one biosimilar to another when a prescription is filled if the company marketing the second biosimilar happens to win a competitive bid with an insurance company, he said.
The filgrastim biosimilar called Zarxio is the only biosimilar currently approved in the United States, but the FDA has received two applications for biosimilars for inflammatory diseases: one from Celltrion for infliximab biosimilar Remsima (August 2014) and one from Sandoz for an etanercept biosimilar (October 2015). In addition to two infliximab biosimilars that have been approved in other countries, one etanercept biosimilar that has been approved in South Korea, and one adalimumab biosimilar approved in India, there are many others in development to treat inflammatory diseases as of July 2015, including 12 for adalimumab, 9 for etanercept, 5 for infliximab, 2 for tocilizumab, and 7 for rituximab, according to Dr. Jonathan Kay, professor of medicine and director of clinical research in the division of rheumatology at the University of Massachusetts, Worcester.
Unresolved regulatory concerns
In separate presentations at the meeting, Dr. Kay described many of the nuances that define biosimilars, which go by different terminology in other countries, such as “follow-on biologic” in Japan, “subsequent-entry biological” in Canada, and “similar biological medicinal product” in the European Union. They are defined as a legitimate copy of an off-patent biopharmaceutical that has undergone rigorous analytical comparison and clinical assessment, in comparison to its reference product, and are approved by a regulatory agency according to a specific pathway for biosimilar evaluation. These differ from biomimetics, which are developed as a replica of a biopharmaceutical but have not been developed, assessed, or approved according to regulatory guidelines for biosimilars.
The FDA takes a “totality of the evidence” approach to establish biosimilarity. The biosimilar pathway for approval is different from the originator pathway by relying more on analytical and preclinical studies and less on the clinical pharmacology and clinical trial data to support biosimilarity.
However, the agency has not yet published final guidance for all steps in demonstrating biosimilarity, particularly for clinical pharmacology data. Draft guidance says the biosimilar must be analyzed and assigned to an assessment grade: not similar, similar, highly similar, and highly similar with fingerprintlike similarity.
During production, both originator and biosimilar biopharmaceuticals can have protein-folding variants, misfolding, aggregation, enzymatic cleavage, and degradation that can lead to inactivation of the protein or increased immunogenicity. Even so, most biosimilars are not identical to the originator because of post-translational modifications, but they do not matter as long as they are not clinically meaningful. Even originator products can drift over time because small changes in manufacturing processes can lead to gradual changes in the molecule, Dr. Kay said.
Extrapolation of indications from the originator to a biosimilar is another area of concern, Dr. Kay said. The FDA will consider the extrapolation of data from a clinical trial of a biosimilar conducted in one disease to support approval for additional indications for which the originator product is already licensed, but not across indications with different mechanisms of action, such as between rheumatoid arthritis and non-Hodgkin’s lymphoma for rituximab. But for which inflammatory diseases should a biosimilar be studied to provide adequate information for extrapolation of indications? Dr. Kay asked. This situation brings about questions of whether dermatologists would be comfortable using a biosimilar that has been studied for rheumatoid arthritis to treat psoriasis or gastroenterologists using a drug with data only from psoriatic arthritis to treat Crohn’s disease or ulcerative colitis.
Both the Coalition of State Rheumatology Organizations and the ACR oppose extrapolation of indications from the clinical trial data of a biosimilar in one disease to support approval of additional indications for which the originator product is already licensed, but Dr. Kay thought that “extrapolation of indications makes perfect sense” because it won’t be possible to review a biosimilar for indications not already approved for the originator and it’s natural to extrapolate to already approved indications once the protein is shown to function nearly identically to the originator.
Ideally, the nomenclature system for biosimilars should clearly identify each product to improve pharmacovigilance and to differentiate between products that have not been determined to be interchangeable, Dr. Kay said. In August, the FDA announced draft guidance proposing that all biopharmaceutical products (originator and biosimilars) would have a nonproprietary name that includes a suffix of four lowercase letters that is devoid of meaning. For example, all products that share a core name such as replicamab would be named replicamab-cznm, replicamab-hixf, and so on, Dr. Kay said. Some people have voiced concern that it would be better for names to have some meaning, such as using an abbreviated name for the developing company along with the nonproprietary name of the originator product, but others noted that method could be problematic when companies merge or are acquired by others.
Dr. Huffstutter disclosed relationships with Janssen, UCB, Lilly, Pfizer, Genentech, Bristol-Myers Squibb, and Celgene. Dr. Kay has received grant and research support from many pharmaceutical companies and has served as a consultant or on an advisory board for many pharmaceutical companies, including those developing biosimilars.
SAN FRANCISCO – A growing number of states are passing laws that set the parameters for how originator biologics may be replaced with biosimilars, and not all of them are helpful to physicians trying to maintain some knowledge and control over how prescriptions for biologics are dispensed, according to speakers at the annual meeting of the American College of Rheumatology.
These laws – now passed by a total of 19 states and Puerto Rico, including 12 in 2015 – address a requirement built into the Biologics Price Competition and Innovation Act of 2009 (part of the Affordable Care Act) that introduced the term “interchangeability” into the biosimilars approval pathway, stating that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” The law also gives 1 year of exclusive marketing rights to the first biosimilar approved as being interchangeable with the reference product.
Although regulations on how the Food and Drug Administration will deem a biosimilar to be interchangeable have yet to be drafted, it’s important for physicians to play an active role in shaping the laws that address interchangeability, said Dr. J. Eugene Huffstutter, a rheumatologist in private practice in Hixson, Tenn., and clinical assistant professor of medicine at the University of Tennessee, Chattanooga.
Dr. Huffstutter encouraged rheumatologists and other physicians to work with their local state medical associations to contact their state legislators to explain to them the need for strict laws on how biosimilars can be dispensed. He suggested that good state legislation on biosimilars should contain provisions stating that:
• Only FDA-approved interchangeable biosimilars can be substituted.
• No substitution can be made with “dispense as written” prescription.
• The prescribing physician must be notified of substitution within 1-5 days by electronic record or fax.
• The pharmacy must maintain a record of the dispensed drug.
Organizations including the ACR, the Coalition of State Rheumatology Organizations, patient groups, electronic prescribers, state medical societies, and pharmaceutical companies (for the most part) support strong state laws on biosimilars, while the pharmacy lobby and insurance companies have opposed them, Dr. Huffstutter said.
The 19 states with biosimilars laws include California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Massachusetts, New Jersey, North Carolina, North Dakota, Oregon, Tennessee, Texas, Utah, Virginia, and Washington, along with Puerto Rico. However, the laws in Oregon and Virginia will sunset in 2016. Another seven states have 2015 or current session legislation on biosimilar substitution: Hawaii, Maryland, Michigan, Mississippi, Oklahoma, Pennsylvania, and Vermont. States with bills that failed or were not acted upon at adjournment include Arizona, Arkansas, Nevada, and Rhode Island, according to information provided to Dr. Huffstutter by the Coalition.
State laws may differ on substitution notification, he noted. In Tennessee, the law (H.B. 572) states that notification should occur in “a reasonable period of time” instead of a defined period. “What may be reasonable for one person may not be reasonable for another. I really think 5 days is the outside time, or 5 business days, because if you’re thinking about some of the biosimilars that are coming down the pike, they’ll be given on a weekly basis, so you’ll at least know before [patients] get their second shot what they’re receiving,” Dr. Huffstutter noted.
Idaho is unique in that it impaneled a board of pharmacy regulation on biosimilar substitution rather than a separate law. It states that “A pharmacist may substitute an interchangeable biosimilar product for a prescribed biological product if the biosimilar has been determined by the FDA to be interchangeable and published in the Purple Book; the prescriber does not indicate by any means that the prescribed biological product must be dispensed; and the name of the drug and the manufacturer or the NDC [National Drug Code] number is documented in the patient medical record.”
The situation may become trickier as more biosimilars are approved, noted Dr. Huffstutter, who is a member of the ACR’s Government Affairs Committee and is a liaison to the Committee on Rheumatologic Care. It could potentially be a problem when a patient is taking a biosimilar for a particular originator biologic and then other biosimilars for that originator join the marketplace. A patient could potentially be switched from one biosimilar to another when a prescription is filled if the company marketing the second biosimilar happens to win a competitive bid with an insurance company, he said.
The filgrastim biosimilar called Zarxio is the only biosimilar currently approved in the United States, but the FDA has received two applications for biosimilars for inflammatory diseases: one from Celltrion for infliximab biosimilar Remsima (August 2014) and one from Sandoz for an etanercept biosimilar (October 2015). In addition to two infliximab biosimilars that have been approved in other countries, one etanercept biosimilar that has been approved in South Korea, and one adalimumab biosimilar approved in India, there are many others in development to treat inflammatory diseases as of July 2015, including 12 for adalimumab, 9 for etanercept, 5 for infliximab, 2 for tocilizumab, and 7 for rituximab, according to Dr. Jonathan Kay, professor of medicine and director of clinical research in the division of rheumatology at the University of Massachusetts, Worcester.
Unresolved regulatory concerns
In separate presentations at the meeting, Dr. Kay described many of the nuances that define biosimilars, which go by different terminology in other countries, such as “follow-on biologic” in Japan, “subsequent-entry biological” in Canada, and “similar biological medicinal product” in the European Union. They are defined as a legitimate copy of an off-patent biopharmaceutical that has undergone rigorous analytical comparison and clinical assessment, in comparison to its reference product, and are approved by a regulatory agency according to a specific pathway for biosimilar evaluation. These differ from biomimetics, which are developed as a replica of a biopharmaceutical but have not been developed, assessed, or approved according to regulatory guidelines for biosimilars.
The FDA takes a “totality of the evidence” approach to establish biosimilarity. The biosimilar pathway for approval is different from the originator pathway by relying more on analytical and preclinical studies and less on the clinical pharmacology and clinical trial data to support biosimilarity.
However, the agency has not yet published final guidance for all steps in demonstrating biosimilarity, particularly for clinical pharmacology data. Draft guidance says the biosimilar must be analyzed and assigned to an assessment grade: not similar, similar, highly similar, and highly similar with fingerprintlike similarity.
During production, both originator and biosimilar biopharmaceuticals can have protein-folding variants, misfolding, aggregation, enzymatic cleavage, and degradation that can lead to inactivation of the protein or increased immunogenicity. Even so, most biosimilars are not identical to the originator because of post-translational modifications, but they do not matter as long as they are not clinically meaningful. Even originator products can drift over time because small changes in manufacturing processes can lead to gradual changes in the molecule, Dr. Kay said.
Extrapolation of indications from the originator to a biosimilar is another area of concern, Dr. Kay said. The FDA will consider the extrapolation of data from a clinical trial of a biosimilar conducted in one disease to support approval for additional indications for which the originator product is already licensed, but not across indications with different mechanisms of action, such as between rheumatoid arthritis and non-Hodgkin’s lymphoma for rituximab. But for which inflammatory diseases should a biosimilar be studied to provide adequate information for extrapolation of indications? Dr. Kay asked. This situation brings about questions of whether dermatologists would be comfortable using a biosimilar that has been studied for rheumatoid arthritis to treat psoriasis or gastroenterologists using a drug with data only from psoriatic arthritis to treat Crohn’s disease or ulcerative colitis.
Both the Coalition of State Rheumatology Organizations and the ACR oppose extrapolation of indications from the clinical trial data of a biosimilar in one disease to support approval of additional indications for which the originator product is already licensed, but Dr. Kay thought that “extrapolation of indications makes perfect sense” because it won’t be possible to review a biosimilar for indications not already approved for the originator and it’s natural to extrapolate to already approved indications once the protein is shown to function nearly identically to the originator.
Ideally, the nomenclature system for biosimilars should clearly identify each product to improve pharmacovigilance and to differentiate between products that have not been determined to be interchangeable, Dr. Kay said. In August, the FDA announced draft guidance proposing that all biopharmaceutical products (originator and biosimilars) would have a nonproprietary name that includes a suffix of four lowercase letters that is devoid of meaning. For example, all products that share a core name such as replicamab would be named replicamab-cznm, replicamab-hixf, and so on, Dr. Kay said. Some people have voiced concern that it would be better for names to have some meaning, such as using an abbreviated name for the developing company along with the nonproprietary name of the originator product, but others noted that method could be problematic when companies merge or are acquired by others.
Dr. Huffstutter disclosed relationships with Janssen, UCB, Lilly, Pfizer, Genentech, Bristol-Myers Squibb, and Celgene. Dr. Kay has received grant and research support from many pharmaceutical companies and has served as a consultant or on an advisory board for many pharmaceutical companies, including those developing biosimilars.
EXPERT ANALYSIS FROM THE ACR ANNUAL MEETING
ACR: Adalimumab best TNFi for anterior uveitis in ankylosing spondylitis
SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.
Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.
There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.
Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.
The results were presented at the annual meeting of the American College of Rheumatology.
Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).
About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.
“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.
In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.
“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.
The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.
The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.
The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.
Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.
Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.
SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.
Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.
There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.
Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.
The results were presented at the annual meeting of the American College of Rheumatology.
Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).
About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.
“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.
In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.
“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.
The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.
The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.
The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.
Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.
Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.
SAN FRANCISCO – Adalimumab was the clear winner over infliximab and etanercept for anterior uveitis in a Scandinavian database study of 1,365 patients with ankylosing spondylitis.
Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab (Humira). Flares per 100 patient-years dropped by almost 70%.
There was less improvement with infliximab (Remicade), which tended to be used in low doses in the study, less than 5 mg/kg. Office visits dropped from 50.4 to 27.3 per 100 patient-years for the 605 patients who started on it. Flares decreased by about 40%.
Etanercept (Enbrel), meanwhile, seemed to make uveitis worse, a concern that’s been raised previously. Office visits for uveitis increased from 38.1 to 56.5 per 100 patient-years for the 354 patients started on etanercept. Flares increased by about 20%.
The results were presented at the annual meeting of the American College of Rheumatology.
Among patients who were uveitis free in the 2 years prior to starting a tumor necrosis factor inhibitor (TNFi), the risk of flare was far greater with etanercept than with adalimumab (adjusted hazard ratio, 3.69; 95% confidence interval, 1.61-8.46). The risk also was higher for infliximab, though not significantly so (adjusted HR, 1.67; 95% CI, 0.69-4.04).
About 2% of adalimumab patients had their first bout of uveitis after starting it, versus 5.3% of infliximab and 13.7% of etanercept patients.
“A clear reduction in uveitis rates was observed for adalimumab, a slight reduction for infliximab, and a marked increase for etanercept, irrespective of the method for counting flares,” reported Dr. Elisabeth Lie, a rheumatology fellow at Gothenburg (Sweden) University.
In the adjusted analysis, “adalimumab and infliximab were associated with significantly lower hazard for first uveitis flare than etanercept,” noted Dr. Lie.
“Right now, we are still favoring infliximab because it comes as a biosimilar, so it’s inexpensive; I think we are giving it the benefit of the doubt. Still, these results are so favorable for adalimumab” that they make “a strong case to at least have a lower threshold to switch to it if you are not successful with your first choice,” Dr. Lie said in an interview.
The etanercept findings are “at least a reminder that if you have a patient with any history of uveitis, choose another option. I’ve seen a few” cases apparently triggered by etanercept. When that happens, “switch to something else,” she said.
The problem with etanercept may be related to its structure or immunologic effects, but no one really knows for sure, she added.
The study linked the first-time use of a TNFi by ankylosing spondylitis patients in the Swedish Biologics Register to their office visits for anterior uveitis as captured in the country’s National Patient Register. Dr. Lie and her coinvestigators analyzed the 2 years before and after the start of a TNFi. Adalimumab was more frequently used toward the end of the study period, which ran from 2003 through 2010.
Patients were in their early 40s, on average, and almost three-quarters were men. Infliximab patients most often used concomitant disease-modifying antirheumatic drugs and had the highest rate of comorbid inflammatory bowel disease, at 10.4%. Adalimumab patients had the lowest median baseline C-reactive protein at 10 mg/L, but highest pretreatment rate of uveitis, at 28%.
Dr. Lie is a speaker and consultant for AbbVie, the maker of adalimumab, and Pfizer, the maker of etanercept.
AT The ACR ANNUAL MEETING
Key clinical point: Pick adalimumab or perhaps infliximab for anterior uveitis in AS, not etanercept.
Major finding: Office visits for uveitis dropped from 42.6 to 13.4 per 100 patient-years for the 406 patients who started on adalimumab; office visits increased from 38.1 to 56.5 per 100 patient-years for the 354 patients who started on etanercept.
Data source: Database study of 1,365 ankylosing spondylitis patients with anterior uveitis.
Disclosures: The presenting investigator is a speaker and consultant for AbbVie, maker of adalimumab, and Pfizer, maker of etanercept.
ACR: Video capsule endoscopy finds Crohn’s disease best in spondyloarthropathy patients
SAN FRANCISCO – Video capsule endoscopy proved superior to ileocolonoscopy in detecting lesions consistent with Crohn’s disease in patients with known spondyloarthropathies in a study presented at the annual meeting of the American College of Rheumatology.
“The incremental yield of CE [capsule endoscopy) was 31% over IC [ileocolonoscopy]. CE changed management in two-thirds of patients in this study. CE should be the first round of tests to detect CD [Crohn’s disease] in patients with SpA [spondyloarthropathies]. This is a ‘game-changer,’ ” stated senior author Dr. Ernest Seidman of McGill University, Montreal.
Although IC can show asymptomatic inflammation of the terminal ileum, it is “ignoring the rest of the small bowel,” he said.
About 5%-10% of patients with SpA manifest with inflammatory bowel disease, whereas 40%-60% of SpA patients have microscopic biological evidence of gut inflammation that typically occurs without symptoms. These patients don’t meet the criteria for inflammatory bowel disease, Dr. Seidman explained.
The study included 64 patients with SpA or ankylosing spondylitis with or without gastrointestinal symptoms; 58% had gastrointestinal symptoms. All patients were taken off NSAIDs for 1 month prior to the study because their use may be associated with inflammation that is indistinguishable from microscopic bowel inflammation. Treatment with anti–tumor necrosis factor biologics was not allowed, with the exception of etanercept. On the day before CE, patients had a liquid diet. CE was performed on all patients first, and then IC was performed.
“The sequence was important,” Dr. Seidman noted.
The investigators used a value of greater than 350 on the Lewis score, a validated measure of inflammatory activity on small-bowel CE, to identify moderate Crohn’s disease.
None of the patients with negative CE had Crohn’s disease; 45.3% had inflammation typical for Crohn’s disease on CE, compared with 14% on IC (P =.036). All positive ileal and colonoscopic biopsies were consistent with Crohn’s disease.
The study also showed that fecal calprotectin levels were significantly correlated with mucosal inflammation observed on CE. However, the presence of gastrointestinal symptoms, C-reactive protein level, and the results from a panel of serologic, inflammatory and genetic tests (a commercial test called IBD sgi Diagnostic) were not predictive of small bowel inflammation in these patients.
AbbVie funded the study. Dr. Seidman reported financial disclosures with Abbott Immunology Pharmaceuticals and Prometheus Laboratories, which he said supplied the video capsules.
SAN FRANCISCO – Video capsule endoscopy proved superior to ileocolonoscopy in detecting lesions consistent with Crohn’s disease in patients with known spondyloarthropathies in a study presented at the annual meeting of the American College of Rheumatology.
“The incremental yield of CE [capsule endoscopy) was 31% over IC [ileocolonoscopy]. CE changed management in two-thirds of patients in this study. CE should be the first round of tests to detect CD [Crohn’s disease] in patients with SpA [spondyloarthropathies]. This is a ‘game-changer,’ ” stated senior author Dr. Ernest Seidman of McGill University, Montreal.
Although IC can show asymptomatic inflammation of the terminal ileum, it is “ignoring the rest of the small bowel,” he said.
About 5%-10% of patients with SpA manifest with inflammatory bowel disease, whereas 40%-60% of SpA patients have microscopic biological evidence of gut inflammation that typically occurs without symptoms. These patients don’t meet the criteria for inflammatory bowel disease, Dr. Seidman explained.
The study included 64 patients with SpA or ankylosing spondylitis with or without gastrointestinal symptoms; 58% had gastrointestinal symptoms. All patients were taken off NSAIDs for 1 month prior to the study because their use may be associated with inflammation that is indistinguishable from microscopic bowel inflammation. Treatment with anti–tumor necrosis factor biologics was not allowed, with the exception of etanercept. On the day before CE, patients had a liquid diet. CE was performed on all patients first, and then IC was performed.
“The sequence was important,” Dr. Seidman noted.
The investigators used a value of greater than 350 on the Lewis score, a validated measure of inflammatory activity on small-bowel CE, to identify moderate Crohn’s disease.
None of the patients with negative CE had Crohn’s disease; 45.3% had inflammation typical for Crohn’s disease on CE, compared with 14% on IC (P =.036). All positive ileal and colonoscopic biopsies were consistent with Crohn’s disease.
The study also showed that fecal calprotectin levels were significantly correlated with mucosal inflammation observed on CE. However, the presence of gastrointestinal symptoms, C-reactive protein level, and the results from a panel of serologic, inflammatory and genetic tests (a commercial test called IBD sgi Diagnostic) were not predictive of small bowel inflammation in these patients.
AbbVie funded the study. Dr. Seidman reported financial disclosures with Abbott Immunology Pharmaceuticals and Prometheus Laboratories, which he said supplied the video capsules.
SAN FRANCISCO – Video capsule endoscopy proved superior to ileocolonoscopy in detecting lesions consistent with Crohn’s disease in patients with known spondyloarthropathies in a study presented at the annual meeting of the American College of Rheumatology.
“The incremental yield of CE [capsule endoscopy) was 31% over IC [ileocolonoscopy]. CE changed management in two-thirds of patients in this study. CE should be the first round of tests to detect CD [Crohn’s disease] in patients with SpA [spondyloarthropathies]. This is a ‘game-changer,’ ” stated senior author Dr. Ernest Seidman of McGill University, Montreal.
Although IC can show asymptomatic inflammation of the terminal ileum, it is “ignoring the rest of the small bowel,” he said.
About 5%-10% of patients with SpA manifest with inflammatory bowel disease, whereas 40%-60% of SpA patients have microscopic biological evidence of gut inflammation that typically occurs without symptoms. These patients don’t meet the criteria for inflammatory bowel disease, Dr. Seidman explained.
The study included 64 patients with SpA or ankylosing spondylitis with or without gastrointestinal symptoms; 58% had gastrointestinal symptoms. All patients were taken off NSAIDs for 1 month prior to the study because their use may be associated with inflammation that is indistinguishable from microscopic bowel inflammation. Treatment with anti–tumor necrosis factor biologics was not allowed, with the exception of etanercept. On the day before CE, patients had a liquid diet. CE was performed on all patients first, and then IC was performed.
“The sequence was important,” Dr. Seidman noted.
The investigators used a value of greater than 350 on the Lewis score, a validated measure of inflammatory activity on small-bowel CE, to identify moderate Crohn’s disease.
None of the patients with negative CE had Crohn’s disease; 45.3% had inflammation typical for Crohn’s disease on CE, compared with 14% on IC (P =.036). All positive ileal and colonoscopic biopsies were consistent with Crohn’s disease.
The study also showed that fecal calprotectin levels were significantly correlated with mucosal inflammation observed on CE. However, the presence of gastrointestinal symptoms, C-reactive protein level, and the results from a panel of serologic, inflammatory and genetic tests (a commercial test called IBD sgi Diagnostic) were not predictive of small bowel inflammation in these patients.
AbbVie funded the study. Dr. Seidman reported financial disclosures with Abbott Immunology Pharmaceuticals and Prometheus Laboratories, which he said supplied the video capsules.
AT THE ACR ANNUAL MEETING
Key clinical point:Video capsule endoscopy is better than ileocolonoscopy for detection of Crohn’s disease in patients with spondyloarthropathies.
Major finding: Video capsule endoscopy detected Crohn’s disease in 45% of patients, compared with 14% detected by ileocolonoscopy (P =.036).
Data source: Prospective study of 64 patients with SpA who underwent video capsule endoscopy followed by ileocolonoscopy.
Disclosures: AbbVie funded the study. Dr. Seidman reported financial disclosures with Abbott Immunology Pharmaceuticals and Prometheus Laboratories, which he said supplied the video capsules.
