Subcutaneous tocilizumab (TCZ-SC) monotherapy or combination therapy can be an effective treatment for rheumatoid arthritis (RA), particularly among patients with inadequate responses to anti-tumor necrosis factor agents or monotherapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), according to research published in Rheumatology.
Researchers conducted a pooled analysis of the TOZURA study program (ClinicalTrial.gov identifiers: NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603 and NCT02046616), a multinational, common-framework phase 4 study program examining the efficacy of TCZ-SC for moderate to severe RA.
Primary outcomes of efficacy, safety, and immunogenicity were evaluated at baseline, 1, 2, and 4 weeks, and then every 4 weeks for 24 weeks. Safety follow-up was assessed for 8 additional weeks.
The 11 study protocols included 1804 patients. Study participants received 162 mg TCZ-SC each week for ≥24 weeks as either monotherapy or combination therapy (19.6% vs 80.4%, respectively); combination therapy was initiated alongside a csDMARD.
In efficacy assessments, disease activity score-28 erythrocyte sedimentation rate (DAS28-ESR) was similar between groups for remission and low and moderate DAS28-ESR, with “comparable” decreases in both groups from baseline to week 24 assessment (mean change, -3.40 and -3.46 in the monotherapy and combination therapy groups, respectively; P <.0001).
Clinical disease activity index rates were also similar between groups for remission and low and moderate disease activity, with a comparably decreased clinical disease activity index score from baseline to week 24 (mean change, 23.54 and -23.83 in the monotherapy and combination therapy groups, respectively; P <.0001 for both). European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) 20/50/70/90 response rates were also similar at week 24: 73.3% and 77.5% of patients achieved an EULAR good response, and 57.2% and 57.7% of patients achieved an ACR50 response in the monotherapy and combination therapy groups, respectively.
Safety assessments indicated that overall adverse event rate was 622.4 per 100 person-years (622.1 vs 622.5 in the monotherapy and combination therapy groups, respectively). The most commonly reported adverse events were infections and infestations (42.0% overall); 6.2% of patients discontinued participation for safety reasons, and 1.6% of patients withdrew “due to insufficient therapeutic response.”
“The TOZURA phase 4 study program demonstrated that TCZ-SC was efficacious in patients with RA, with combination therapy and monotherapy being comparably effective and with the observed safety profile being consistent with the known TCZ profile,” the researchers concluded.
Disclosures: Drs Choy, Caporali, Xavier, Fautrel, Bao, Bernasconi, and Pethö-Schramm report various relationships with pharmaceutical companies including Eli Lilly, Janssen, Novartis, and Pfizer. For a complete list of disclosures, please see the full study text.
Choy E, Caporali R, Xavier R, et al. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries [published online December 13, 2017]. Rheumatology. doi:10.1093/rheumatology/kex443