Background Tocilizumab administered subcutaneously (TCZ-SC) has been approved for the treatment of rheumatoid arthritis (RA) both as mono- and combination therapy.
Objectives To evaluate the efficacy and safety of TCZ-SC 162 mg once weekly (qw) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 24 weeks in adult patients (pts) with moderate to severe RA.
Methods TOZURA is a multinational, open-label, single-arm umbrella program comprising 7 single-country and 4 regional multicountry protocols (total 22 countries). Pts enrolled were inadequate responders to DMARD, and previous biologic DMARDs were allowed in 8 of 11 protocols. Pts received TCZ-SC 162 mg qw for 24 weeks administered at the investigator's discretion as monotherapy or in combination with a csDMARD. Stable oral NSAIDs and corticosteroids (CS), ≤10 mg/day prednisone or equivalent, were allowed. Efficacy and safety were evaluated at weeks 1, 2, 4 and every 4 weeks for 24 weeks (plus 8 weeks for safety). Propensity score-based matching was used for between-group tests.
Results Of 1804 pts treated, 353 (19.6%) received monotherapy (mono) and 1451 (80.4%) combination therapy (combo); 349 pts (19.3%) had received a prior biologic DMARD. Background characteristics: 81.6% female; mean age, 54.1 years; mean RA duration, 7.7 years; and 82.7% seropositive –similar between treatment groups. Baseline CS was less frequent in the mono vs combo group (41.1% vs 51.2%); however, the mean prednisone equivalent daily dose was similar (6.6 vs 6.5 mg/day, respectively). Pts who continued TCZ to week 24 based on Kaplan-Meier estimates (95% CI) were 79.3% (74.7%>83.2%) for mono and 85.6% (83.7%>87.3%) for combo. DAS28 scores decreased comparably from baseline to week 24 in both groups (mean change: mono −3.40 and combo −3.46), with no significant difference between groups (P =0.61). Results were similar for the Clinical Disease Activity Index (CDAI, mean change by week 24: −23.5 and −23.8, with no significant difference between groups: P=0.42). The proportion of pts who achieved DAS28 or CDAI-based remission, low disease activity or ACR20/50/70/90 responses was similar between groups (Figure 1). In all, 18.2% of pts withdrew; 6.4% did so for safety reasons (mono 9.1%, combo 5.8%). AE rates were similar between groups (Table). Serious AE (SAE) rates were 14.6/100 PY (mono: 22.8/100 PY, combo: 12.8/100 PY). Serious infection and infestation rates were 3.6/100 PY (mono: 4.0/100 PY, combo: 3.5/100 PY) – similar between groups. Six deaths occurred (0.64/100 PY), 1 in the monotherapy group (0.57/100 PY) and 5 in the combination (0.65/100 PY) group.
Conclusions TCZ-SC demonstrated convincing and comparable efficacy as mono- and combination therapy in pts with RA as was previously observed with TCZ-IV. The safety profile of TCZ-SC is consistent with the known safety profile of TCZ as monotherapy and in combination with csDMARDs.
Acknowledgements Funded by F. Hoffmann-La. Roche, Ltd.
Disclosure of Interest E. Choy Grant/research support from: F. Hoffmann-La Roche, Chugai Pharmaceutical, Consultant for: F. Hoffmann-La Roche, Chugai Pharmaceutical, Speakers bureau: F. Hoffmann-La Roche, Chugai Pharmaceutical, R. Caporali Consultant for: AbbVie, Bristol-Myers Squibb, F. Hoffmann-La Roche, UCB and MSD Pharmaceuticals, R. Xavier Consultant for: F. Hoffmann-La Roche, Pfizer, Janssen Pharmaceuticals, AbbVie, Eli Lilly and Company, Speakers bureau: F. Hoffmann-La Roche, Pfizer, Janssen Pharmaceuticals, Abbvie, Eli Lilly and Company, B. Fautrel: None declared, R. Sanmarti: None declared, C. Bernasconi Employee of: F. Hoffmann-La Roche (contractor), A. Pethö-Schramm Employee of: F. Hoffmann-La Roche