Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes

Abstract

Introduction: Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.

Objectives: To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.

Methods: A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.

Results: The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.

Conclusions: Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.

Keywords: arthritis, psoriatic; biological therapy; outcome assessment, health care.

Figure 1

PRISMA flow diagram. NMA, network meta-analysis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCTs, randomised controlled trial; SLR, systematic literature review.* Bibliographies of eligible SLR/ NMAs were reviewed to identify any RCTs that met the inclusion criteria and then excluded. # Bibliographies of eligible pooled analyses were reviewed to identify relevent RCTs that met the inclusion criteria.and included only if data were not reported in the individual RCTs.

Figure 2

Network diagram for ACR response note that the node size denotes total number of patients randomised to that treatment; edge line thickness denotes total number of studies informing that comparison. ACR, American College of Rheumatology; BID, twice daily; BIW, twice weekly; IV, intravenous; LD, loading dose; MTX, methotrexate; QD, once daily; QW, weekly; Q2W, every two weeks; Q4W, every four weeks; Q8W, every eight weeks; Q12W, every twelve weeks.

Figure 3

Forest plot of treatment effects for key comparators versus placebo on ACR response. ACR overall treatment effect was based on a random-effects model with placebo adjustment. median treatment effects and 95% credible intervals are plotted on the probit scale. Key comparators include bDMARDs at doses licensed for use in PSA or PSO. ACR, American College of Rheumatology; bDMARD, biological disease modifying anti-rheumatic drug; BIW, twice weekly; MTX, methotrexate; PSA, psoriatic arthritis; PSO, psoriasis; QD, once daily; QW, weekly; Q2W, every two weeks; Q4W, every four weeks; Q8W, every eight weeks; Q12W, every twelve weeks.

Figure 4

Forest plot of treatment effects for key comparators versus placebo on PASI response. *Based on a combination of studies reporting outcomes at week 12 or 16 and week 24; †Based on studies reporting outcomes at week 24 only note that PASI treatment effect was based on a fixed-effects model with placebo adjustment. Median treatment effects and 95% credible intervals are plotted on the probit scale. Key comparators include bDMARDs at doses licensed for use in PSA or PSO. bDMARD, biological disease modifying antirheumatic drug; BIW, twice weekly; PASI, Psoriasis Area and Severity Index; PSA, psoriatic arthritis; PSO, psoriasis; Q2W, every two weeks; Q4W, every four weeks; Q8W, every eight weeks; Q12W, every twelve weeks.

Figure 5

Forest plot of treatment effects for key comparators versus placebo on resolution of enthesitis (A) and dactylitis (B). *Based on a combination of studies reporting outcomes at week 12 or 16 and week 24; †Based on studies reporting outcomes at week 24 only. Note that treatment effect on resolution of enthesitis was based on a random-effects model with placebo adjustment. Treatment effect on resolution of dactylitis was based on a fixed-effects model with placebo adjustment. Key comparators include bDMARDs at doses licensed for use in PSA or PSO. bDMARD, biological disease modifying antirheumatic drug; CrI, credible interval; PSA, psoriatic arthritis; PSO, psoriasis; Q2W, every two weeks; Q4W, every four weeks; Q8W, every eight weeks.