Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study

Abstract

Objectives: The aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients.

Methods: SIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored.

Results: Three hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P =0.0001) and CDAI (P =0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs.

Conclusion: Real-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old.

Trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686.

Keywords: DAS28; clinical activity index; monotherapy; rheumatoid arthritis; steroid; subcutaneous; tocilizumab.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

Study population flow chart AE: adverse event; n: number of patients in group. Subgroups: 1L: first line = tocilizumab after failing conventional synthetic DMARDs before enrolment; 2L: second line = tocilizumab after failing one biologic before enrolment; 2L+: third line = tocilizumab after failing two or more biologics before enrolment.

Fig. 2

CS tapering in patients with DAS28 remission Dosages (in milligrams per month) of oral CS therapy in the intention-to-treat (ITT) population (n = 333) at the time of first tocilizumab therapy (V1: enrolment, n = 160, blue) vs the final visit (EOS: end of study, n = 99, green), plotted as box plots.

Fig. 3

Disease activity and remission rates in the intention-to-treat and treatment subgroups Mean DAS28 ESR (A), DAS28 CRP (B) and CDAI (C) scores, respectively, plotted as line charts by visits (V1, V2, V3 and EOS). Symbols denote significant differences between subgroups: †P < 0.005, DAS28 ESR 1L vs 2L at V1 (1L > 2L); ‡P < 0.05, DAS28 CRP 1L vs 2L at V1 (1L > 2L); §P < 0.005, DAS28 ESR 1L vs 2L at V3 (2L > 1L); *P < 0.05, CDAI 1L vs 2L at V3 (2L > 1L); #P < 0.05, DAS28 ESR 1L vs 2L at EOS (2L > 1L); $P < 0.01, CDAI 1L vs 2L at EOS (2L > 1L). Percentage of patients achieving remission (yes: green; no: yellow) evaluated by DAS28 ESR (D), DAS28 CRP (E) and CDAI (F) scores, plotted as stacked bar charts.

Fig. 4.

Disease activity and remission rate in age subgroups Mean DAS28 ESR (A), DAS28 CRP (B) and CDAI (C) scores plotted as line charts by visits (V1, V2, V3 and EOS). Symbols denote significant differences between subgroups: *P < 0.05 at the DAS28 ESR as ‘<45’ < ‘>75’ at V1; ‡P < 0.02 at the DAS28 ESR as ‘45–55’ < ‘>75’ at V1; †P < 0.05 at the DAS28 ESR as ‘55–65’ < ‘>75’ at V1; ¤P < 0.05 at the DAS28 ESR as ‘<45’ < ‘65–75’ at V2; *P < 0.05 at the DAS28 ESR as ‘<45’ < ‘>75’ at V3; ‡P < 0.05 at the DAS28 ESR as ‘45-55’ < ‘>75’ at V3; #P < 0.05 at the DAS28 ESR as ‘65–75’ < ‘>75’ at V3; *P < 0.02 at the DAS28 ESR as ‘<45’ < ‘>75’ at EOS; ‡P < 0.05 at the DAS28 ESR as ‘45–55’ < ‘>75’ at EOS; †P < 0.05 at the DAS28 ESR as ‘55–65’ < ‘>75’ at EOS; #P < 0.05 at the DAS28 ESR as ‘65–75’ < ‘>75’ at EOS; §P < 0.05 at the DAS28 CRP as ‘<45’ < ‘45–55’ at V2; $P < 0.05 at the DAS28 CRP as ‘<45’ < ‘55–65’ at V2; ¤P < 0.05 at the DAS28 CRP as ‘<45’ < ‘65–75’ at V2; $P < 0.005 at the DAS28 CRP as ‘<45’ < ‘55–65’ at V3; ¤P < 0.05 at the DAS28 CRP as ‘<45’ < ‘65–75’ at V3; *P < 0.002 at the DAS28 CRP as ‘<45’ < ‘>75’ at V3; $P < 0.05 at the CDAI as ‘<45’ < ‘55–65’ at EOS; %P < 0.05 at the CDAI as ‘45–55’ < ‘55–65’ at EOS. Percentage of patients achieving remission (yes: green; no: yellow) in age groups evaluated by DAS28 ESR (D) and CDAI (E) scores, presented as stacked bar charts. Sample size was insufficient for DAS28 CRP age subgroup assessment.