Indirect comparisons of the efficacy of biological agents in patients with psoriatic arthritis with an inadequate response to traditional disease-modifying anti-rheumatic drugs or to non-steroidal anti-inflammatory drugs: A meta-analysis☆
Introduction
Psoriatic arthritis (PsA) is a chronic seronegative inflammatory arthritis characterized by not only the presence of peripheral arthritis, but also enthesitis, dactylitis, and spondylitis [1], [2]. It is present in up to 30% of patients with psoriasis with an estimated prevalence of 0.3%–1.0% in general population [3], [4]. PsA is associated with increased morbidity and mortality, resulting in a reduced quality of life and productivity [5], [6], [7].
Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), particularly methotrexate, are the conventional first-line treatments for PsA although this therapeutic strategy has largely been derived from clinical experience with rheumatoid arthritis with only limited number of randomized controlled trials (RCTs) [8], [9]. The clinical response to this therapy is often unsatisfactory. In fact, a recent meta-analysis of therapies of PsA has demonstrated that the efficacy of NSAIDs, methotrexate, sulfasalazine, and leflunomide were minimal [10], leaving an unmet therapeutic need.
Over the past 2 decades, with a better understanding of the immunopathogenesis of PsA and the development of biotechnology, novel therapeutic options have been introduced. Tumor necrosis factor (TNF) inhibitors (etanercept, infliximab, adalimumab, golimumab and more recently, certolizumab) were the first group of biologic agents approved for PsA, followed by an interleukin (IL)-12 and IL-23 inhibitor (ustekinumab), and a phosphodiesterase-4 inhibitor (apremilast). The efficacy of all of these biologic agents in patients who had persistently active disease despite traditional DMARDs/NSAIDs or who could not tolerate DMARDs/NSAIDs has been well demonstrated in RCTs [11].
The increasing availability of these biologic DMARDs suggests the need to establish the comparative efficacy of these agents. However, to date, there is only one RCT that directly compared between the three older TNF inhibitors (etanercept, infliximab, and adalimumab) [12].
Indirect comparison meta-analysis is a statistical technique used to estimate the relative effect of two interventions by comparing to a common comparator (placebo group) when a direct comparison is not available. In fact, two recent meta-analyses have utilized this technique and did not find any statistically significant difference between the response rates for the four older TNF inhibitors (etanercept, infliximab, adalimumab, and golimumab) [13], [14]. However, the data on the relative efficacy of the more novel agents (certolizumab, ustekinumab, apremilast, and secukinumab) are not available. Therefore, we conducted this systematic review and meta-analysis to compare the relative efficacy of all available biologic agents in patients with PsA who experienced inadequate response or intolerance of traditional DMARDs or NSAIDs.
Section snippets
Search strategy
Two investigators (P.U. and C.T.) independently searched published studies indexed in Medline, Cochrane Central, and EMBASE database from inception to November, 2014 using the combination of search terms described in Supplementary data 1 without any language restrictions. References of selected articles were also manually searched.
Inclusion criteria
The inclusion criteria that were established a priori were as follows: (1) RCTs published as original studies comparing the efficacy of biologic agents to placebo in
Systematic review of the literature
Our search strategy yielded 270 potentially relevant articles. After exclusion of 77 duplicate articles, 193 articles underwent title and abstract review. A total of 144 articles were excluded based on this abstract review as they were clearly not relevant to our research question, leaving 49 articles for full-length article review. Of them, 24 articles were excluded because of duplication between databases. Nine studies were excluded because they did not report our outcome of interest, while
Discussion
PsA was once considered as a milder form of systemic arthritis. However, recent data have demonstrated that the disease is more aggressive than previously thought. In a cohort study, up to 50% of patients with early disease had radiographic erosive changes in the first 2 years [35]. This data prompts physicians to treat PsA more aggressively.
DMARDs, particularly methotrexate, and NSAIDs are generally used as the first-line therapy for PsA as reflected in the Group for Research and Assessment of
Conclusion
Our study demonstrated that patients with PsA who did not have an adequate response from or could not tolerate DMARDs/NSAIDs had a higher probability of achieving the ACR20 response with older TNF inhibitors (etanercept, infliximab, adalimumab, and golimumab) and secukinumab at the dose of 150 mg and 300 mg weekly, compared with apremilast, certolizumab, and ustekinumab. However, this analysis has some limitations. Therefore, head-to-head comparisons are required to confirm these findings.
Acknowledgment
Patompong Ungprasert: Study design, literature search, statistical analysis, and writing article.
Charat Thongprayoon: Literature search and revising article.
John Davis: Study design and revising article.
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Cited by (34)
Psoriatic arthritis and psoriasis in the era of COVID-19
2022, Autoimmunity, COVID-19, Post-COVID19 Syndrome and COVID-19 VaccinationRecommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology
2021, Journal of the Formosan Medical AssociationCitation Excerpt :In case of contraindication, intolerance, or inadequate response to TNFi or IL-17i, IL-12/23 inhibitors (IL-12/23i) may be considered.76 Although there is insufficient evidence to recommend the use of any single biologic over another biologic, a recent systematic review and network meta-analysis of 29 randomized controlled trials (RCTs) comprising 10,204 participants and 17 treatments found that infliximab, adalimumab, golimumab, secukinumab, and ustekinumab were relatively safer and more efficacious in the treatment of active PsA, as compared to other biologics or tsDMARDs,77 and earlier meta-analyses also provide support for these results.78,79 For enthesitis and dactylitis, a recent systematic review and meta-analysis of 18 RCTs involving 6981 patients found that newer agents such as ixekizumab, secukinumab, and ustekinumab had the same efficacy as TNFi (infliximab, golimumab, and adalimumab), and there was no evidence to recommend any biologic over another as initiation therapy.80
Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis
2020, Current Therapeutic Research - Clinical and ExperimentalCitation Excerpt :Although these results support our findings for ACR20, a strength of the current NMA is that it assessed the relative efficacy of multiple active treatments across several end points. Additionally, a published meta-analysis has shown that indirect comparisons of the TNFi agents etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol with apremilast, ustekinumab, and secukinumab demonstrated that patients with PsA have a higher probability of achieving ACR20 with etanercept, infliximab, adalimumab, golimumab, and secukinumab than other agents.44 Another meta-analysis conducted indirect comparisons of 4 non-TNFi bDMARDs (ie, abatacept, apremilast, secukinumab, and ustekinumab) and reported that the likelihood of achieving ACR20 in the TNFi-IR population with PsA did not differ significantly between these agents.45
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Conflict of interest statement: John M. Davis is a site investigator for trials sponsored by Pfizer and Roche/Genentech. Division of Rheumatology, Mayo clinic receives research funding from Pfizer for John M. Davis׳s role on a grant.