Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence

Abstract

Objective.To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention.Methods.Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004–2014 were analyzed. Kaplan-Meier curves and Cox regression models were used.Results.Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26–0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24–0.50 for 28-joint Disease Activity Score remission).Conclusion.The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis

“…This is mainly seen in the use of MTX with infliximab and adalimumab and has been more widely studied in RA cohorts or a mixed cohort of patients with RA, spondyloarthritis (SpA), psoriasis and inflammatory bowel disease . Specifically in PsA, co‐administration of MTX with TNFi did not result in significant differences in clinical response but was found to improve drug survival especially in patients receiving infliximab . The majority of guidelines reviewed did not comment on the combination of a biologic with csDMARDs but when stated, there was insufficient evidence to provide a firm recommendation .…”

“…62 Specifically in PsA, co-administration of MTX with TNFi did not result in significant differences in clinical response but was found to improve drug survival especially in patients receiving infliximab. 64,65 The majority of guidelines reviewed did not comment on the combination of a biologic with csDMARDs but when stated, there was insufficient evidence to provide a firm recommendation. 35,66 The Canadian Rheumatology Association/…”

Patient sex does not affect endoscopic outcomes of biologicals in inflammatory bowel disease but is associated with adverse events

“…The same holds true in rheumatology patients treated with biologicals. Several studies reported an association between patient sex and adverse events [87] and drug retention rates [88,89], whereas other studies found no such association [90].…”

Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

“…RA and spondyloarthritis patients are included in the HeRBT at the initiation of first bDMARD and are followed-up for as long as they receive bDMARDs. Detailed analysis of protocol is given elsewhere [6,11]. Treatment decisions (bDMARD selection, co-medication, dosage adjustments/switches) were made at the discretion of treating rheumatologists based on clinical assessments, national guidelines, and patient's preferences.…”