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Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

ABSTRACT: Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.

SUBMITTER: Yiu ZZN

PROVIDER: S-EPMC5832757 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Yiu Zenas Z N ZZN Smith Catherine H CH Ashcroft Darren M DM Lunt Mark M Walton Shernaz S Murphy Ruth R Reynolds Nick J NJ Ormerod Anthony D AD Griffiths Christopher E M CEM Warren Richard B RB

The Journal of investigative dermatology 20171017 3

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohort ...[more]

PMID: 29054603

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Project description:BackgroundThe 'treat to target' paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis.ObjectivesTo identify treatment targets in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA).MethodsData from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate-severe, severe) and PASI (range 0-72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA.ResultsData from 13 422 patients were available (58% male, 91% white ethnicity, mean age 44·9 years), including over 23 000 longitudinal PASI and PGA scores. An absolute PASI ? 2 was concordant with PASI 90 and an absolute PASI ? 4 was concordant with PASI 75 in 90% and 88% of cases, respectively. These findings were robust to subgroups of timing of assessment, baseline disease severity and treatment modality. PASI and PGA were strongly correlated (Spearman's rank correlation coefficient 0·92). The median PASI increased from 0 (interquartile range 0-0, range 0-23) to 19 (interquartile range 15-25, range 0-64) for PGA clear to severe, respectively. PGA clear/almost clear was concordant with PASI ? 2 in 90% of cases, and PGA moderate-severe severe was concordant with the National Institute for Health and Care Excellence PASI eligibility criteria for biologics in 81% of cases.ConclusionsAn absolute PASI ? 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis. What's already known about this topic? The most commonly used relative disease activity measure in psoriasis is ? 90% improvement in Psoriasis Area and Severity Index (PASI 90); however, it has several limitations including dependency on a baseline severity assessment. Defining an absolute target disease activity end point in psoriasis has the potential to improve patient outcomes and reduce costs, as demonstrated by treat-to-target approaches in other chronic diseases such as hypertension and diabetes. The Physician's Global Assessment (PGA) is a popular alternative measure of psoriasis severity in daily practice; however, its utility has not been formally assessed with respect to PASI. What does this study add? An absolute PASI ? 2 corresponds with PASI 90 response and is a relevant disease end point for treat-to-target approaches in psoriasis. There is a strong correlation between PASI and PGA. PGA moderate-severe/severe may serve as an alternative eligibility criterion for biologics to PASI-based definitions, and PGA clear/almost clear is an appropriate alternative absolute treatment end point. What are the clinical implications of this work? Absolute PASI ? 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis.

Project description:BACKGROUND:The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. OBJECTIVES:To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. METHODS:Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis-? inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. RESULTS:We included 5468 biologic-naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25-p75) follow-up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16-3.21), 1.93 (1.05-3.34), 1.94 (1.09-3.32), 1.92 (0.93-3.45) and 1.43 (0.84-2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41-2.22); ustekinumab vs. adalimumab: 0.81 (0.30-2.17); etanercept vs. adalimumab: 0.81 (0.28-2.30)] and methotrexate against adalimumab [1.05 (0.34-3.28)]. CONCLUSIONS:In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow-up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.

Project description:ImportanceTreatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies.ObjectivesTo assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated.Design, setting, and participantsThis comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed.Main outcomes and measuresThe primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial.ResultsA total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses.Conclusions and relevanceThis comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.

Project description:IntroductionIn the USA, psoriasis affects approximately 3% of the population and costs more than $110 billion annually. The development of targeted biologics has revolutionized psoriasis management, but at an increasing cost. According to Joint AAD/NPF guidelines, an important need exists to identify biomarkers that can predict the appropriate biologic agent for patients.MethodsA survey of community dermatologists was developed to address (1) significant factors influencing biologic therapy utilization in psoriasis; (2) the clinical utility of a test stratifying biologic response.ResultsRespondents confirmed that trial and error leads to frequent biologic switching. The survey indicated that 82% of dermatologists switch 10-30% of their patients in the first year and 98% switch intra-class for at least 50% of non-responding patients. The trial and error is due, in part, to formularies influencing the physician 77% of the time, with only 14% reporting that their first choice and the formulary alignment is greater than 75%. Compounding trial and error, 93% of the physicians report that they wait at least 12 weeks before determining non-response, in alignment with AAD/NPF guidelines. The lack of precision medicine and this trial-and-error approach result in unnecessary wasted spending and suboptimal patient outcomes. After being given an overview of Mind.Px, a dermal biomarker patch used to predict therapeutic response to a biologic class, survey participants expressed that: 93% would utilize Mind.Px results to determine first-line therapy even if this differed from initial clinical choice 100% would utilize Mind.Px if part of the prior authorization process 98% say Mind.Px would improve patient outcomes 81% reported Mind.Px would help with prior authorization process CONCLUSIONS: Surveyed dermatologists believe a test that predicts psoriasis treatment response to a class of biologic drugs would lessen trial and error, provide a tool for physicians to make more informed decisions about drug selection, improve patient outcomes, and significantly reduce wasted spending.

Project description:Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-α) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.

Dataset Information

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Publications

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Similar Datasets

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