Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland

Abstract

BackgroundMultiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice.ObjectiveTo compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management.MethodsThis observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors.Results4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs.ConclusionTofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.

Tofacitinib: Real-World Data and Treatment Persistence in Rheumatoid Arthritis

“… Multicentre, retrospective ANSWER study Assess retention rates and reasons for discontinuation for 7 bDMARDs and TOF in in bDMARD-naïve and bDMARD-switched RA patients NA Significant differences between agents for drug retention in bDMARD-naïve and bDMARD-switched patients TOF drug discontinuation rates (bDMARD-switched patients): ineffectiveness, 22.8%; ADRs, 13.2%, non-ADR reasons, 7.7%; remission, 2.3%; all-causality AEs, 38.5% Croiteru et al 2019 27 Israeli RA registry (January 2010–February 2019) 864 treatment courses: TCZ (297), ETN (242), ABT (115), TOF (111), GOL (99) Prospective cohort study Real-life retention of TOF in RA TCZ had longer drug persistence compared with TOF, ETN, ABT & GOL TOF median drug persistence was 15.8 months (95% CI: 8.6–23.1) and non-inferior to ETN (26.4 months, 95% CI: 5.9–46.9; p=0.426), ABT (20.3 months, 95% CI: 9.8–30.9; p=0.157), and GOL (15.1 months, 95% CI: 5.9–24.3; p=0.698) Mueller et al 2019 28 Swiss St. Gallen & Aarau Cohorts (January 2015 – April 2017) 144 Retrospective cohort study Assess the clinical tolerability and effectiveness of TOF Initiated on TOF 5 mg BID Mean DAS28 decreased significantly from 4.4 at baseline to 3.13 at 360 days. Discontinuation rate during follow-up (mean 1.22 years), 38.2%: due to insufficient response (14.6%), AEs (23.6%) 53% achieved LDA & 48% DAS28-defined remission Finckh et al 2020 29 Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM-RA) Registry 2600 patients and 4023 treatment courses: TNFi (1862); bDMARDs-OMA (1355); TOF (806) initiators Observational nested cohort study Overall drug retention TOF ≤5 mg bd (96.6%); >5–10 mg BID (3.4%) TOF drug maintenance comparable with non-TNFi bDMARDs and significantly higher than TNFi Overall drug maintenance: HR=1.29 (95% CI: 1.14–1.47) for TOF vs TNFi; HR=1.09 (95% CI: 0.96–1.24) for TOF vs non-TNFi bDMARDs 47% monotherapy;53% combination with csDMARDs Zengin et al 2018 30 Turkish nationwide TURKBIO registry 180 …”

“…Discontinuation was most commonly due to ineffectiveness with lower rates for tofacitinib (46%) compared with non-TNFi bDMARDs (50%) and TNFi (57%). 29 …”

“…Analysis of the Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM-RA) Registry found that drug maintenance in tofacitinib initiators (n = 806) was significantly higher than TNFi initiators (n = 1862) and comparable with non-TNFi bDMARDs (eg, rituximab, tocilizumab, abatacept) initiators (n = 1355). Median (IQR) drug maintenance was 25 months (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) 1.24) for both non-TNFi bDMARDs and tofacitinib. Discontinuation was most commonly due to ineffectiveness with lower rates for tofacitinib (46%) compared with non-TNFi bDMARDs (50%) and TNFi (57%).…”

“…Discontinuation was most commonly due to ineffectiveness with lower rates for tofacitinib (46%) compared with non-TNFi bDMARDs (50%) and TNFi (57%). 29 A retrospective analysis of RA patients (n = 180) in the Turkish nationwide TURKBIO registry showed that tofacitinib significantly reduced VAS pain scores, DAS28, HAQ and C-reactive protein (CRP) from baseline to week 60. 30 Tofacitinib persistence rates were 75% at 48 weeks and 48% at 137 weeks.…”

Exploring the Role of Interleukin-6 Receptor Inhibitor Tocilizumab in Patients with Active Rheumatoid Arthritis and Periodontal Disease

“…On the other hand, several papers have addressed the effect of specific periodontal therapies (e.g., non-surgical scaling and root planning) on clinical RA activity in patients with chronic periodontitis with controversial results [ 37 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. The most recent data from the ESPERA (Experimental Study of Periodontitis and Rheumatoid Arthritis) cohort failed to demonstrate clinical improvement in established RA following aggressive and intensive periodontal treatment [ 57 ].…”