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

Background: Multiple 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.

Objective: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management.

Methods: This 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.

Results: 4023 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.

Conclusion: Tofa 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.

Keywords: abatacept; biological therapies; comparative effectiveness research; rheumatoid arthritis; tocilizumab; tumour necrosis alpha inhibitors.

Figure 1

Drug discontinuation for any reason in patients with RA on TNFi, bDMARD-OMA and Tofa. TNFi=TNF inhibitors. OMA=bDMARDs with other modes of action (abatacept and anti–IL6 receptor), Tofa=Tofacitinib. Adjusted survival curves based on 4023 treatment courses with 2103 events, representing the average patient in the SCQM population: a female seropositive, non-smoking patients with one prior b/tsDMARD, a female seropositive, non-smoking patient with one prior b/tsDMARD, mean age of 57, disease duration of 10.5 years, baseline DAS28 of 3.7, BMI of 26, who initiated her treatment before the launch of a second JAKi. (A) The median (95% CI) drug maintenance in years for the selected combination of covariates was: Tofa: 1.86 (1.52 to 2.3), OMA: 1.69 (1.48 to 2.1) and TNF: 1.32 (1.15 to 1.6) years. The multiple adjusted HRs of drug discontinuation was: HR_{OMA versus Tofa}=1.09 (0.97 to 1.24), HR_{TNF versus Tofa}=1.29 (1.14 to1.47). The overall p-value for treatment effect was <0.001. Tofa 397 events, OMA bDMARD 689 events and TNFi 1017 events. (B) The multiple adjusted HRs of drug discontinuation due to ineffectiveness was: HR_{TNF versus Tofa}=1.59 (1.33 to 1.89) and HR_{OMA versus Tofa}=1.19 (0.99 to 1.43). Tofa 183 events, OMA bDMARD 347 events and TNFi 580 events. (C) The multiple adjusted HRs of drug discontinuation due to intolerance and adverse events was: HR_{OMA versus Tofa}=0.74 (0.58 to 0.96), HR_{TNF versus Tofa}=0.76 (0.59 to 0.98). Tofa 126 events, OMA bDMARD 191 events and TNFi 199 events. The difference in the total of events of panel A and the sum of events due to insufficient effectiveness or safety from panels B and C is due to discontinuation events due to ‘other’ reasons, which are not represented.

Figure 2

TNFi=TNF inhibitors. OMA=biologic with other modes of action (abatacept and anti-IL-6 receptor), Tofa=tofacitinib. Adjusted survival curves based on 4023 treatment courses with 2103 events, representing the average patient in the SCQM population: a female seropositive, non-smoking patients with one prior b/tsDMARD, mean age of 57, disease duration of 10.5 years, baseline DAS28 of 3.7, BMI of 26, who initiated her treatment before the launch of a second JAKi. The median (95% CI) retention time in years for this selected combination of covariates was: For TNFi: HR_-MONO: 1.27 (1.08 to 1.49); for bDMARDs-OMA: HR_{-MONO versus COMBO}: 1.03 (0.89 to 1.20); for Tofa 1.11 (0.91 to 1.35), respectively.