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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”
  1. E. Choy1,
  2. R. Caporali2,
  3. R. Xavier3,
  4. B. Fautrel4,
  5. R. Sanmarti5,
  6. C. Bernasconi6,
  7. A. Pethö-Schramm6
  1. 1Cardiff University, Cardiff, United Kingdom
  2. 2University of Pavia, Pavia, Italy
  3. 3Universidade Federal do Rio Grande do Sul Porto Alegre, Rio Grande do Sul, Brazil
  4. 4Pierre and Marie Curie University, Paris, France
  5. 5Universitat de Barcelona, Barcelona, Spain
  6. 6F. Hoffmann-La Roche AG, Basel, Switzerland

Abstract

Background 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.

Objectives 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.

Methods 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 investigator's 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.

Results 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; P <0.0001 for both) with no significant difference between groups (P =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, P <0.0001 for both groups: between groups P =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).

Conclusions 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.

Disclosure of Interest 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

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