FRI0215 Subcutaneous Tocilizumab as Monotherapy or in Combination with A csDMARDs in Patients with Rheumatoid Arthritis – Interim Analysis of A Large Phase IV International Umbrella Study, “Tozura”
Authors: E. Choy, R. Caporali, R. Xavier, B. Fautrel, R. Sanmarti, C. Bernasconi, A. Pethö-Schramm
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Tocilizumab (TCZ), administered as intravenous (TCZ-IV) and subcutaneous (TCZ-SC) formulations, has been approved for treatment of patients (pts) with rheumatoid arthritis (RA) both as mono- and combination therapy. <h3>Objectives</h3> To evaluate the efficacy and safety of TCZ-SC 162 mg once weekly (qw) as monotherapy and in combination with conventional synthetic DMARDs (csDMARDs) over 24 weeks in adult pts with moderate to severe RA. <h3>Methods</h3> TOZURA is a multinational, open-label, single-arm umbrella study comprising 7 single-country and 4 regional multicountry protocols. It aimed to enroll $≈ $ 1,850 pts who were biological DMARD inadequate responders (IR; 8/11 protocols) and/or csDMARD-IR (11/11 protocols). Pts received TCZ-SC 162 mg qw for 24 weeks, administered at the investigator9s discretion as monotherapy or in combination with a csDMARD. Stable oral NSAIDs and corticosteroids (CCS), ≤10 mg/day prednisone or equivalent, were allowed. Efficacy and safety were evaluated at weeks 1, 2, 4 and every 4 weeks thereafter. <h3>Results</h3> In this interim analysis, 1246 pts were included by end of 2014; 283 pts received monotherapy, 963 combination; 25% of pts were biologic DAMRD-IR (monotherapy: 36%, combination: 22%). Background characteristics: 80.5% female, mean age 54.5 years, mean RA disease duration 7.7 years and 81.4% seropositive – similar between treatment groups. Baseline oral CCS use was less frequent in the mono- group (42.8%) than in the combination group (51.2%); however, their mean dose was similar (6.673 vs 6.505 mg/day, respectively). Pts continuation of TCZ at week 24 based on Kaplan-Meier estimates (95% CI) were 0.784 (0.732, 0.828) for mono- and 0.855 (0.831, 0.875) for combination therapy. All pts had significant reductions in mean 28-joint Disease Activity (DAS28) scores by week 24 (mean decrease: monotherapy 3.41 and combination 3.44; <i>P</i> &lt;0.0001 for both) with no significant difference between groups (<i>P</i> =0.788). Results were similar for the Clinical Disease Activity Index (CDAI), which does not include acute phase reactants (mean change by week 24: 24.03 and 23.28, <i>P</i> &lt;0.0001 for both groups: between groups <i>P</i> =0.629). The proportion of pts who achieved DAS28 or CDAI-based remission and low disease activity and ACR20/50/70/90 responses was similar between the treatment groups (Figs 1A, 1B). Of the 231 pts (18.5%) who withdrew, 92 (7.4%) did so for safety reasons (29 [10.2%] monotherapy, 63 [6.5%] combination). Serious AEs (SAEs) occurred in 78 pts (6.3%; 11.5/100 PY) and rates of AEs and SAEs were similar between groups (Table 1). Serious infections and infestations occurred in 18 pts (1.4%; 2.2/100 PY), with similar rates between groups. Five deaths occurred, 1 in the monotherapy group (coronary artery disease) and 4 in the combination group (intestinal ischemia, myocardial infarction, pneumonia, septic shock). <h3>Conclusions</h3> TCZ-SC demonstrated convincing and comparable efficacy in mono- and combination therapy in pts with RA as 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. <h3>Disclosure of Interest</h3> E. Choy Grant/research support from: F. Hoffmann-La Roche and Chugai Pharmaceutical, Consultant for: F. Hoffmann-La Roche and Chugai Pharmaceutical, Speakers bureau: F. Hoffmann-La Roche and 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 Pharmaceutica, Abbvie, Eli Lilly and Company, Speakers bureau: F. Hoffmann-La Roche, Pfizer, Janssen Pharmaceutica, Abbvie, Eli Lilly and Company, B. Fautrel: None declared, R. Sanmarti: None declared, C. Bernasconi Employee of: F. Hoffmann-La Roche, A. Pethö-Schramm Employee of: F. Hoffmann-La Roche