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

Abstract

IntroductionRandomised 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.ObjectivesTo 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.MethodsA 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.ResultsThe 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.ConclusionsDespite 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.

Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities

“…Similarly, other anti-TNF-α agents (adalimumab, infliximab, and certolizumab) also demonstrated a significant impact on the signs and symptoms in patients with PsA and have been approved for clinical use [19][20][21]. In a network meta-analysis of 46 RCTs comparing the efficacy of various systemic therapies for active PsA, anti-TNF therapies ranked highest in the ACR response [22]. Therefore, we recommend anti-TNF-α agents as the first-line option (Table 1).…”

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…Systemic anti-metabolites (such as methotrexate), cyclosporin, and retinoids (such as acitretin) are also available. Other systemic therapies such as apremilast (a PDE4 inhibitor), tumor necrosis factor (TNF)-alpha inhibitors, and other biologic agents that block interleukins (ILs) (such as inhibitors of IL-17, IL-23, and IL-12/23) are utilized for patients with more extensive psoriasis; in addition, Janus kinase (JAK) inhibitors (tofacitinib and upadacitinib) have recently been added to the pharmacologic armamentarium for psoriatic arthritis [15][16][17][18][19][20].…”

Medicom Conference Report EULAR 2022

“…However, in the double-blind, phase 3, EXCEED trial (NCT02745080), resolution rates of enthesitis were similar when secukinumab was compared with adalimumab [13]. In a network meta-analysis of phase 3 studies on the PsA treatment, the efficacy and safety of different DMARDs were compared, with a special focus on bDMARDs [14]. According to this analysis, guselkumab, IL-17 inhibitors (secukinumab, ixekizumab, brodalumab), and adalimumab were similarly efficacious in the resolution of enthesitis (see Figure ).…”