Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open‐Label Trial

Abstract

Objective. To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission.Methods. RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission.Results. In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups.Conclusion. Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

“…Patients with IR to DMARDs received TCZ 162 mg s.c. weekly for 24 weeks in the ToSpace open-label RCT and those achieving DAS28-ESR <2.6 (at week 20 and week 24) were randomised to continue TCZ 162 mg weekly or switch to TCZ 162 mg every 2 weeks for 24 weeks. Seventy-three per cent of patients switched to TCZ Q2W could maintain DAS28-ESR <2.6 at week 48 vs 90% continuing weekly TCZ treatment (p=0.004) 48…”

Canadian Rheumatology Association Living Guidelines for the Pharmacological Management of Rheumatoid Arthritis With Disease-Modifying Antirheumatic Drugs

“… The majority of the evidence relates to anti-TNF therapy, although results for other mechanisms of action that have been studied appear similar, including rituximab (11), abatacept (12), tocilizumab (13) and baricitinib (trial studied the reduction of 4mg/day dose to the approved dose in Canada of 2 mg/day) (14).…”

Risk of flare after tapering or withdrawal of biologic/targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or axial spondyloarthritis: a systematic review and meta-analysis

“…No studies were identified for patients with PsA or a mixed population of IA. Of the included trials, 64% were funded by the drug manufacture (29,30,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) with no difference between RA or axSpA (12/18 trials [67%] vs. 3/5 trials [60%], respectively). However, significantly more withdrawal studies (10/11 trials [91%]) were funded by the manufacture compared to tapering trials (8/16 trials [50%]).…”