Literature Review of 2019 EULAR Recommendations for PsA Management Indicates Efficacy, Safety of Pharmacologic Treatment

There are no uniform guidelines regarding DMARD tapering. EULAR guidelines suggest RA pharmacotherapy should be de-escalated in the following order: glucocorticoids, biologic DMARDs, and, finally, conventional DMARDs, with each treatment stopping completely before de-escalation of the next agent in the sequence.[4] Numerous DMARD dose-tapering protocols have been studied, including immediate discontinuation of treatment. When the goal is to withdraw treatment, the ACR recommends an initial dose-tapering phase to enable better monitoring of patient response and candidacy for discontinuation.[5] The ACR also strongly encourages patient involvement in decisions regarding their individual DMARD tapering protocol.
There are no uniform guidelines regarding DMARD tapering. EULAR guidelines suggest RA pharmacotherapy should be de-escalated in the following order: glucocorticoids, biologic DMARDs, and, finally, conventional DMARDs, with each treatment stopping completely before de-escalation of the next agent in the sequence.[4]
Numerous DMARD dose-tapering protocols have been studied, including immediate discontinuation of treatment. When the goal is to withdraw treatment, the ACR recommends an initial dose-tapering phase to enable better monitoring of patient response and candidacy for discontinuation.[5] The ACR also strongly encourages patient involvement in decisions regarding their individual DMARD tapering protocol.
Researchers performed a review of the efficacy and safety of disease-modifying antirheumatic drugs in psoriatic arthritis.

Both biologic and synthetic disease-modifying antirheumatic drugs (DMARDs) are effective in reducing symptoms of psoriatic arthritis (PsA), according to literature review data published in Annals of Rheumatic Diseases. Results from this review informed the development of the 2019 European League Against Rheumatism (EULAR) recommendations for PsA management.

Investigators conducted a systematic literature search of Medline, Embase, and Cochrane Library for publications reporting DMARD treatment in adult patients with PsA. Studies published between 2015 and 2018 were eligible for inclusion in the review. Drug efficacy was assessed using data from randomized controlled trials; safety data were extracted from cohort studies, case-control studies, and long-term extension studies. Primary efficacy end points included signs and symptoms of PsA, defined according to the American College of Rheumatology response criteria, the Psoriasis Area Severity Index, and other validated composite measures. The primary adverse events of interest were laboratory abnormalities, infections, malignancies, cardiovascular events, gastrointestinal events, depression, and/or suicide attempts. Risk for bias was assessed using the Cochrane Collaboration’s Risk of Bias tool; study quality was appraised using the Newcastle-Ottawa Scale.

Of 5528 articles screened, 181 were assessed for eligibility and 56 were selected for full text review of efficacy and safety (efficacy, n=33). Studied biologic DMARDs included tumor necrosis factor inhibitors (TNFi; n=6 studies; golimumab, etanercept, adalimumab biosimilar, etanercept biosimilar), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), and IL-23-p19 inhibitors (n=2; guselkumab, risankizumab). One study each reported the efficacy of clazakizumab (IL-6) inhibitor, abatacept (CD80/86 inhibitor), and ABT-122 (anti-TNF/IL-17A inhibitor). Efficacy data were also available for targeted synthetic DMARDs, including phosphodiesterase-4 inhibitors (n=5; apremilast) and Janus kinase (JAK) inhibitors (n=2; tofacitinib, filgotinib). Overall, the reviewed studies supported the efficacy of biologic and synthetic DMARDs in reducing PsA symptoms. Three articles investigated DMARD tapering and indicated that withdrawal from DMARDs could be successfully performed without flare-ups. In a trial of patients with primary entheseal disease, ustekinumab was found to be superior to TNF inhibitor therapy.

Safety data were extracted from 13 long-term extension studies, 9 cohort studies, and 1 case-cohort study. No new safety signals were identified. Injection site reactions and infections were the most common adverse events. Cancer and major adverse cardiovascular events were rare; however, in studies of patients with other rheumatic diseases, JAK inhibitors were associated with increased risk for venous thromboembolic events. Although these events were not observed among patients with PsA, regulators have extended a warning for all patients receiving JAK inhibitors.

Results from this literature review informed the updated EULAR recommendations for PsA treatment. Biologic and synthetic DMARDs were widely effective in treating a range of PsA symptoms. No new safety signals were identified.

The primary limitation of this review was the between-study heterogeneity, which prevented meta-analysis; instead, study results were reported narratively. Even so, these results provide substantial evidence for the efficacy and safety of the pharmacologic treatment of PsA.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Kerschbaumer A, Smolen JS, Dougados M, de Wit M, Primdahl J, McInnes I, et al. Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis [published online May 7, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217163