Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

Abstract

ObjectiveTo compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA).MethodsIn this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments.ResultsAt week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group.ConclusionsTreatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237.

Inflammation and the Silent Sequelae of Stroke

“…And, as with depression, the administration of proinflammatory cytokines [e.g., interleukin (IL)-6] is associated with the perception of fatigue [49]. Further, treatment with cytokine antagonists is associated with a decrease in fatigue-administration of exogenous IL-1ra (anakinra) decreases fatigue in patients with Sjögren's syndrome [50], and the tumor necrosis factor (TNF)-α receptor antagonist infliximab and the IL-6 receptor antagonist toclizumab reduce fatigue in patients with cancer and autoimmune diseases [51][52][53][54][55].…”

“…Treatment with exogenous IL-1ra (anakinra), for instance, decreases fatigue in patients with Sjögren's syndrome [50]. Similarly, the TNF-α receptor antagonist infliximab and the IL-6 receptor antagonist tocilizumab reduce fatigue in patients with cancer [51] and a variety of autoimmune diseases [52][53][54][55]. Fatigue is a particularly prevalent problem for patients with multiple sclerosis (MS) [117].…”

IL12/IL23 Inhibition in the Treatment of Psoriatic Arthritis

“…In particular, studies analyzing the efficacy of oral DMARDs have shown no improvement over placebo in the case of methotrexate [26,27] and small effect sizes for sulfasalazine [28]. One phase IIb study did reveal efficacy for leflunomide for the joints only, but a phase III study was never performed [29].…”

Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

“…The treatment of PsA with a combination of 2 conventional disease‐modifying antirheumatic drugs (DMARDs) 20, 21 or a DMARD plus a TNF inhibitor has been reported 10, 11, 15, 22. However, clinical trials simultaneously inhibiting 2 cytokines, TNF and IL‐17A, with biologics have not been reported in patients with PsA.…”