Article Text
PDF
Abstract
Introduction An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients.
Objectives To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA.
Methods A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response.
Results The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the ‘without MTX’ subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70.
Conclusions Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.
- psoriatic arthritis
- methotrexate
- autoimmune diseases
- biological therapy
Data availability statement
Data are available on reasonable request. The full NMA report is available on reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
WHAT IS ALREADY KNOWN ON THIS TOPIC
Randomised trials have shown concomitant use of methotrexate (MTX) increases the efficacy of tumour necrosis factor inhibitors in rheumatoid arthritis, but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The lack of such studies justifies the need to conduct a network meta-analysis (NMA).
WHAT THIS STUDY ADDS
The NMA found that the use of concomitant MTX added little-to-no efficacy for the achievement of American College of Rheumatology 20% or 50% improvement responses when used in combination with biologics in the treatment of PsA in patients who had ongoing PsA disease activity despite treatment with MTX . These findings add to the limited body of evidence on the efficacy of concomitant MTX with biologics (at the class level) approved for the treatment of PsA compared with biologic monotherapy.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Because the NMA found the use of concomitant MTX with biologics did not add significant improvement in joint efficacy in the treatment of PsA in patients who had inadequate response to MTX, clinicians should consider biologic monotherapy.
Introduction
Psoriatic arthritis (PsA) is a chronic, systemic, immune-mediated, inflammatory arthritis that can lead to irreversible joint damage and affects around 30% of patients with plaque psoriasis.1–3 Common manifestations of PsA include enthesitis, dactylitis, spondylitis and skin and nail psoriasis. Patients also have increased risk for medical comorbidities including cardiovascular disease, hypertension, dyslipidaemia and insulin resistance, among others.1 This disease profile represents a tremendous burden on a patient’s quality of life.
A common clinical question encountered in rheumatology and dermatology practice is whether to use methotrexate (MTX) in combination with biologics in the treatment of patients with PsA. Available therapies include conventional synthetic disease-modifying antirheumatic drugs (csDMARDS) and biologics (tumour necrosis factor inhibitors (TNFi); interleukin-17 inhibitors (IL-17i); and IL-23i), among others.4 Although MTX is not approved to treat PsA in the USA, it is the most commonly used csDMARD for PsA and moderate-to-severe psoriasis.5 EULAR, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and American College of Rheumatology (ACR) recommend the use of MTX for peripheral arthritis in PsA.6 MTX is frequently used as a first-line monotherapy treatment or in combination with TNFi in patients with rheumatoid arthritis (RA), as studies have demonstrated improved efficacy and reduced immunogenicity.7–11
Similar prescribing practices may carry over to PsA, but randomised clinical trial evidence to support the use of MTX in the population of patients with PsA is limited.12–14 In a recent study, a majority (65%) of people with PsA preferred to avoid the use of MTX when possible due to long-term safety risks or desire to avoid using an additional prescription medication.15 With respect to MTX in combination with biologics in PsA, the available evidence shows minimal to no difference in efficacy with biologic monotherapy versus biologics combined with MTX.12 A 2021 meta-analysis of clinical trial data reported that while, in psoriasis, combination therapy of biologics with MTX was superior to monotherapy in biologics in clinical efficacy outcomes, in PsA, there was no significant difference.16 Thus, despite the use of MTX in combination with different classes of biologics, little-to-no benefit has been shown in the treatment of PsA.
The study reported here evaluates, via network meta-analysis (NMA) and informed by a previously conducted systematic literature review (SLR), the efficacy of biologic monotherapies by treatment class (TNFi, IL-23i and IL-17i) compared with biologics in combination with MTX for the treatment of PsA.
Methods
Study design
An SLR was performed, followed by Bayesian NMA.
Systematic literature review
The SLR was conducted for the following PsA therapies: biologic monotherapy (separated by mechanism of action (MOA): TNFi, IL-23i and IL-17i) and biologics with MTX (separated by MOA: TNFi, IL-23i and IL-17i).
The search was performed for dates ranging from 1977 through 29 January 2022 and included adults with active PsA. The search included randomised, double-blind, controlled phase II and phase III trials, inclusive of post hoc analyses. The search excluded phase I randomised controlled trials (RCTs); phase IV clinical trials; open-label studies; case studies; single group designs; observational studies; cohort studies; cross-sectional designs; letters; commentaries; and reviews.
Databases searched were PubMed (which includes MEDLINE), Embase, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov. The selection of the databases listed above was consistent with the National Institute for Health and Care Excellence (NICE) guidelines on process and methods17 and the Cochrane Handbook for Systematic Reviews of Interventions.18
Conference proceedings of ACR and EULAR, formerly the EULAR, were searched to identify relevant studies not yet published in journal format.
Database searches were supplemented by manual searches of the websites of manufacturers of interventions included in the review, as well as hand searches of citations from relevant studies and the prior literature reviews. For the final stage of hand searching for reports of clinical trials identified through the trial registries, Google Scholar was used for targeted searches of associated publications and reports.
Each identified reference was screened independently by two reviewers at both levels. If needed, more than two independent reviewers were involved to perform each level of study selection to expedite the screening process. All reviewers performed a test selection on a common segment of the references and compared results to ensure consistency in application of the predetermined eligibility criteria. Discrepancies in selection were evaluated to confirm uniform application of the eligibility criteria.
Interventions included the following drugs as monotherapy and in combination with MTX: TNFi (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, investigational agents for which there is data from completed phase III trials), IL-23i (guselkumab, risankizumab and tildrakizumab, investigational agents for which there is data from completed phase III trials) and IL-17i (ixekizumab and secukinumab, investigational agents for which there is data from completed phase III trials). Bimekizumab phase III results were not available during the time frame searched. Included studies were assessed for bias using the Cochrane risk of bias tool V.2.0.18
Additional SLR details are in the supporting materials (online supplemental material).
Supplemental material
Supplemental material
Network meta-analysis
The NMA modelling approach followed the standard requirements from established evidence-based medicine societies like the Cochrane Collaboration19 and NICE.20 Interventions from the SLR evaluated in the NMA based on feasibility were TNFi (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab), IL-23i (guselkumab, risankizumab) and IL-17i (secukinumab, ixekizumab). Studies on the efficacy of tildrakizumab were not evaluated because this drug is not approved for the treatment of PsA. The rationale for grouping by MOA was to study whether MTX provided any additional efficacy in combination with biologics approved for the treatment of PsA (at the class level) versus biologic monotherapy (at the class level). As the majority of studies in PsA included patients with active disease despite being treated with MTX (thereby considered MTX inadequate responders), we excluded the assessment of MTX in monotherapy from this NMA.
Outcomes extracted from the SLR evaluated in the NMA based on feasibility were ACR 20%, 50% and 70% improvement response (ACR20, ACR50, ACR70, respectively), minimal disease activity (MDA) response, very low disease activity response, Psoriasis Area Severity Index 75% response (PASI75), tender joint count, swollen joint count, X-ray damage (van der Heijde modified Sharp Score), Health Assessment Questionnaire Disability Index and any adverse event (AE), including any serious AEs (online supplemental table 1).
Placebo was the reference treatment in models where placebo data were available. Placebo data included trials and post hoc analyses that presented data for placebo alone, not allowing for MTX or other csDMARD use, or from placebo arms that reported outcomes by the subgroups with concomitant MTX and without concomitant MTX. In this case, the ‘without concomitant MTX’ subgroup of the placebo arm was used as the placebo alone arm.
All data were extracted by one researcher and then checked by a second researcher for completeness and accuracy. Extraction discrepancies were resolved by consensus between the two researchers or by arbitration or unilateral decision by a project co-lead investigator.
Bayesian models were performed in WinBUGS V.1.4.321 using the normal likelihood and identity link functions for continuous outcomes and either binomial likelihood and logit link functions for dichotomous outcomes from trials of equal length or binomial likelihood and cloglog link for dichotomous outcomes from trials of varying lengths. Both fixed effects and random effects models were coded and run for all outcomes, based on example code from the National Institutes of Health and Clinical Excellence (NICE) Decision Support Unit.20 All models were performed using three Monte Carlo chains. History plots were produced on the first 1000 iterations to assess mixing. For efficacy outcomes, an additional 49 000 burn-in iterations were run on which trace plots and autocorrelation diagnostics were performed. Then, an additional 50 000 iterations were run on which density plots and Gelman-Rubin diagnostics were performed, and results, deviance information criterion (DIC) and residual deviance were reported. To minimise the amount of autocorrelation, thinning (keeping only the nth iteration) was employed with all models, with the minimum set to 5. Monte Carlo sampling error was calculated and compared with 5% of the SD error threshold. Data handling and plots were performed in R using the ‘r2winbugs’ package.
The fit of Bayesian models was assessed using DIC and residual deviance. The fixed effects model was chosen unless the random effects model produced a distinctly better model fit, generally a 3+ reduction in DIC.21
A result was considered ‘statistically significant’ if it fell outside the 95% credible interval of the posterior distribution.
Heterogeneity was assessed visually by inspecting for each outcome the resultant forest, Gelman-Rubin and leverage plots for the magnitude and variability of the results of each study. In addition, heterogeneity was assessed by evaluating the following parameters: between-studies variance and the difference between fixed and random effects in treatment estimate assessed by a visual inspection (they are expected to be similar if between-study variability was low).
Results
Network meta-analysis
An SLR was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses search guidelines. The search strategy is summarised in figure 1 and additional full SLR details are presented in the online supplemental material.
Systematic literature review and Preferred Reporting Items for Systematic Reviews and Meta-Analyses search. ICTRP, International Clinical Trials Registry Platform; MTX, methotrexate; NMA, network meta-analysis.
Database searches identified 3367 articles. Exclusion of duplicate documents yielded 2180 articles. Titles and abstracts were then examined, leading to the exclusion of 1970 references and the addition of 6 references added via a hand search. The resulting 216 references were examined by full-text review and 148 were excluded. A total of 68 references remained representing 31 clinical trials, of which 17 studies reported results for the ‘without concomitant MTX’ subgroup of interest in addition to the other subgroups for this NMA (figure 1). All trials had low risk in the performance, detection and reporting bias domains. FUTURE 2 had some concerns in the selection bias domain, and NCT00317499 had high risk in the attrition domain.
Outcomes of interest in NMA
Treatments identified in the SLR included in the NMA were TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), IL-23i (guselkumab, risankizumab) and IL-17i (ixekizumab, secukinumab).
Based on the feasibility analysis, 12 efficacy outcomes of interest had enough data to generate networks to run an NMA. These outcomes and the number of trials reporting data for each outcome in the ‘without concomitant MTX’ subgroup are presented in online supplemental table S1. The number of trials was the most robust for ACR20 (15 trials) followed by ACR50 (10 trials); as such, ACR20 and ACR50 efficacy results are presented in figures 2–7. 22–46 The remaining outcomes had fewer trials (range: 2–8 trials).
Network diagram for ACR20. In total, 15 studies and 43 arms were included. Three studies included pooled data from two separate trials. Placebo was used as the reference treatment. Labels are treatment (number of arms using treatment included in NMA). ACR20, American College of Rheumatology 20%; IL, interleukin; MTX, methotrexate; NMA, network meta-analysis; TNFi, tumour necrosis factor inhibitor.
Efficacy results for ACR20 comparing treatment classes. A) TNFi and B) IL-17 inhibitors. ACR20, American College of Rheumatology 20%; FE, finite element; IL-17i, interleukin-17 inhibitor; IL-23i, interleukin-23 inhibitor; TNFi, tumour necrosis factor inhibitor.
Efficacy results for ACR20 comparing treatments without and with MTX. A) TNFi, B) IL-17 inhibitors, and C) IL-23 inhibitors. ACR20, American College of Rheumatology 20%; FE, finite element; IL-17i, interleukin-17 inhibitor; IL-23i, interleukin-23 inhibitor; MTX, methotrexate; TNFi, tumour necrosis factor inhibitor.
Network diagram for ACR50. In total, 10 studies and 25 arms were included. Three studies included pooled data from two separate trials. MTX was used as the reference treatment. Labels are treatment (number of arms using treatment included in NMA). ACR50, American College of Rheumatology 50%; IL, interleukin; MTX, methotrexate; TNFi, tumour necrosis factor inhibitor.
Efficacy results for ACR50 comparing treatment classes. A) TNFi and B) IL-17 inhibitors. ACR50, American College of Rheumatology 50%; FE, finite element; IL, interleukin; MTX, methotrexate; TNFi, tumour necrosis factor inhibitor.
Efficacy results for ACR50 comparing treatments without and with MTX. A) TNFi, B) IL-17 inhibitors, and C) IL-23 inhibitors. ACR50, American College of Rheumatology 50%; FE, finite element; IL, interleukin; MTX, methotrexate; TNFi, tumour necrosis factor inhibitor.
The overall timeframe for all trials and outcomes was 12–156 weeks. By outcome (online supplemental table S1), the ranges were ACR20: 12–54 weeks; ACR50: 12–156 weeks; and ACR70: 12–52 weeks. Doses included in the biologic study arms were limited to approved doses for PsA (MTX is not approved to treat PsA).
ACR20 response results from NMA
The network diagram for ACR20 and the trials included in the network by treatment class are shown in figure 2.
A total of 15 studies and 43 arms were included. Only three trials included IL-23i, with and without concomitant MTX, which limited the strength of results for this class of biologic. There was no notable difference in fit between the fixed effects and random effects models for ACR20, and there was sufficient ACR20 data to be confident both models were a good fit to the data. The fixed effects model is presented in figure 3 (comparison of treatment classes without MTX) and figure 4 (comparison of treatment without and with MTX) as well as online supplemental figure 1 (comparison of treatment classes without and with MTX).
All active treatments were significantly better than placebo with respect to ACR20 (all biologic treatment classes, with and without concomitant MTX) (online supplemental figure 1). Credible intervals were narrow and did not approach 1.
When comparing classes of biologics used as monotherapy (figure 3), IL-23i was not significantly different than TNFi, but IL-17i demonstrated greater efficacy than TNFi (HR 1.33 with 95% credible interval 1.14–1.55). No significant difference was demonstrated between IL-17i and IL-23i monotherapy. Figure 4 presents each biologic class in combination with MTX as a reference compared with the same biologic used alone. No significant differences were demonstrated in TNFi, IL-17i or IL-23i combination with MTX as compared with TNFi, IL-17i or IL-23i monotherapy, respectively. Additional results for ACR20 are shown in online supplemental figure 1.
ACR50 response results from NMA
The network diagram for ACR50 and the trials included in the network by treatment class are shown in figure 5.
There were 10 studies and 25 arms included, and the reference treatment was MTX. Only two trials reported placebo arms, and only one trial included IL-23i with and without concomitant MTX. Those comparisons were entirely dependent on one or two data points, which tempers any possible conclusions regarding IL-23i and placebo. As before, the random effects and fixed effects models were fitted to the data similarly, and the fixed effects model for ACR50 is presented in figures 6 and 7 and online supplemental figure 2.
There were no significant differences between TNFi, IL-17i and IL-23i monotherapy in achieving ACR50 (figure 6). Similarly, ACR50 efficacy was similar for TNFi, IL-17i and IL-23i without and with concomitant MTX (figure 7), although IL-23i data were limited and IL-23i results should be interpreted with caution.
All biologic classes with and without MTX were significantly better than placebo for ACR50 response (online supplemental figure 2A). Additional results are shown in online supplemental figure 2. ACR70 response showed similar trends to ACR50 response, although data were limited (online supplemental figures 3–6). MDA and PASI75 responses trended similarly to ACR20/50/70 responses, although data for these measures were also limited and should be interpreted with caution (online supplemental figures 7–14).
Discussion
In this NMA, all biologic treatment classes had comparable efficacy as monotherapy or in combination with MTX for rates of achieving ACR20 and ACR50 response. Additionally, the IL-17i treatment class in monotherapy and in combination with MTX was significantly more effective than TNFi monotherapy with respect to ACR20 response. IL-23i were comparable in monotherapy and in combination with MTX to TNFi monotherapy, but the robustness of this result may be impacted by the limited IL-23i data available in this NMA. Taken together, these results strongly suggest that, in PsA, biologic monotherapy could serve as an alternative treatment strategy over the combination of MTX with biologics for the treatment of patients with active joint disease despite prior treatment with MTX. Therefore, MTX does not appear to be necessary as a background therapy when a biologic is used for achievement of ACR20 or ACR50 responses in these patients.
Patients’ preferences have a critical role in the selection of treatments at the individual level. Many patients with PsA prefer treatment regimens that do not include MTX.15 Based on the results of this NMA, biologic monotherapy could be a preferred approach for these patients.
Previously published meta-analyses and real-world studies have also evaluated aspects of the use of biologics as monotherapy and biologics in combination with MTX. A 2021 meta-analysis of randomised clinical trial data reported that for PsA, there was no significant difference in efficacy from using biologics as monotherapy versus biologics with MTX; however, for psoriasis, the use of biologics with MTX was superior to biologics as monotherapy.16 In comparison, our meta-analysis focused on PsA alone, analysed therapies at a class level, and included IL-23i therapies for PsA.
A 2015 real-world study using data from the CorEvitas registry found that patients with PsA had similar rates of TNFi persistence and time to Clinical Disease Activity Index remission in patients on TNFi monotherapy and combination therapy.47 However, previous real-world analyses have reported that patients receiving biologics with concomitant MTX had better drug survival than those receiving biologics monotherapy.48 49
A key limitation of this analysis was the paucity of data due to the low number of studies comparing biologic monotherapy to combination therapy with MTX. In the SLR search, articles tended to report either MTX arms or ‘without concomitant MTX’ arms, but rarely reported ‘with and without concomitant MTX’ arms. Thus, not all outcomes could be assessed in this NMA due to feasibility. This feature also limited the main study to presentation of ACR outcomes; other outcomes are included in online supplemental material. Many other NMAs share this drawback.
Another key limitation was that most studies did not include MTX treatment-naive patients. The majority of data included were for patients treated with combination therapy who were inadequate responders to MTX, with the exception of the SEAM-PsA study, which enrolled MTX-naive patients.12 Because this NMA limited the parameters of the literature search to approved dosages of individual therapies, the effects of different dosages of each therapy were not examined. Another potential weakness of this analysis is that patients were not stratified by baseline characteristics, particularly any previous failure or intolerance to biologics. In addition, this analysis was unable to address whether patients on MTX had different characteristics compared with patients not on MTX, such as longer duration of disease or more active disease.
Other outcomes that could not be assessed included safety, which was not possible due to inconsistency of outcomes across studies, as trials often did not break out safety by ‘with and without concomitant MTX’ treatment and thus did not meet the minimum standards for inclusion in the NMA. Furthermore, the NMA focused solely on peripheral PsA because few trials have reported outcomes in axial PsA for the treatments assessed here. Another limitation of this analysis is it did not evaluate whether concomitant MTX improves drug survival (cohort studies were excluded), as has been known in RA for decades. However, studies comparing the efficacy of TNFi monotherapy to TNFi plus MTX revealed no substantial improvement with combination therapy.50
Limitations common to NMA analyses are also considered. An NMA makes a comparison of treatments in a specific disease state using the direct and indirect evidence available and relies on treatment effects reported by RCTs. In RCTs, randomisation controls for observed and unobserved population differences between treatment arms, but this is not true for an NMA since patients are not randomly selected between trials. RCTs included in the NMA may not have identical designs, and heterogeneity between trials and patient populations can exist. However, if sufficient RCTs are available, an NMA may be able to control for observed differences in effect modifiers. Effect modifiers include any differences between RCTs that affect the estimation of treatment effect. These can include population differences, trial design differences and outcome definition differences, among others. Importantly, we included MTX alone in the network diagrams for connectivity purposes and therefore did not exclude major studies here. For outcomes where too few RTCs have been identified to make strong conclusions, published results should note those conclusions are limited by the paucity of studies included.
In conclusion, the current study is one of the first NMAs to evaluate this topic, which helps indirectly compare studies in an area where not many RCTs with comparative data are available in PsA. While MTX use has been consistently shown to provide benefit in combination with biologic therapies for the treatment of RA, less evidence exists to support the benefit of using MTX in combination with biologics for the treatment of PsA with active disease despite being treated with MTX. In this NMA, all biologic treatment classes had comparable ACR20/50 response as monotherapy or in combination with MTX for the treatment of patients with PsA. Considering the full body of evidence and that MTX is not approved for the treatment of people with PsA, the results of this NMA suggest MTX does not provide additional efficacy in joint endpoints when used in combination with biologics in patients with prior inadequate MTX response. Clinicians could consider that biologic monotherapy may be a better option as first-line treatment over combination therapy with MTX for patients with PsA.
Data availability statement
Data are available on reasonable request. The full NMA report is available on reasonable request.
Ethics statements
Patient consent for publication
Acknowledgments
The authors would like to acknowledge Medical Decision Modeling for their partnership with Eli Lilly and Company in preparing data presented in this manuscript. Eli Lilly and Company would like to thank the clinical trial participants and their caregivers, without whom this work would not be possible. The authors also acknowledge Melody Pupols, Lydia Morris, Nicole Lipitz and Dana Melbourne (employees of Syneos Health) for medical writing and editorial assistance with the preparation of the manuscript, funded by Eli Lilly and Company.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors PJM: conception of the work, acquisition of the work, interpretation of data for the work, critical revision of the work for important intellectual content, and guarantor of the work. SReddy and JRL: analysis of data for the work, interpretation of data for the work and critical revision of the work for important intellectual content. DEF and KG: interpretation of data for the work and critical revision of the work for important intellectual content. SRoss: conception of the work, design of the work, acquisition of data for the work, analysis of data for the work, interpretation of data for the work and critical revision of the work for important intellectual content. PR: conception of the work, analysis of data for the work, interpretation of data for the work and critical revision of the work for important intellectual content. CS and AV: design of the work, interpretation of the work and critical revision of the work for important intellectual content.
Funding This study was funded by Eli Lilly and Company.
Competing interests PJM has received research grants, consulting fees and/or speaker fees from AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma and UCB Pharma. SReddy has received consulting fees or served on advisory boards for UCB, Novartis, Fresenius Kabi, Amgen, AbbVie, Janssen and Pfizer; has served as a treasurer for the Psoriasis and Psoriatic Arthritic Clinics Multicenter Advancement Network; and has served on the medical board for the National Psoriasis Foundation. DEF has received grant and/or research support from Emerald, Kadmon, PICORI, Pfizer, Prometheus, Talaris and Mitsubishi and has served as a consultant to AbbVie, Novartis and Pfizer. SRoss, JRL, PR, KG, CS and AV are employees and shareholders of Eli Lilly and Company. AV has received consulting fees from AbbVie, Amgen, BMS, Eli Lilly and Company, Genentech, Janssen, Merck, Novartis, Pfizer and UCB.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.