Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA)

Abstract

Objectives: To evaluate the long-term efficacy and safety of subcutaneous (SC) tocilizumab (TCZ) versus intravenous (IV) TCZ, including switching formulations, in patients with rheumatoid arthritis (RA) and inadequate response to disease-modifying antirheumatic drugs (DMARDs).

Methods: Patients (n=1262) were randomised 1:1 to receive TCZ-SC 162 mg weekly (qw)+placebo-IV every four weeks (q4w) or TCZ-IV 8 mg/kg q4w+placebo-SC qw in combination with DMARD(s). After a 24-week double-blind period, patients receiving TCZ-SC were re-randomised 11:1 to TCZ-SC (n=521) or TCZ-IV (TCZ-SC-IV, n=48), and patients receiving TCZ-IV were re-randomised 2:1 to TCZ-IV (n=372) or TCZ-SC (TCZ-IV-SC; n=186). Maintenance of clinical responses and safety through week 97 were assessed.

Results: The proportions of patients who achieved American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints remission and improvement from baseline in Health Assessment Questionnaire Disability Index ≥0.3 were sustained through week 97 and comparable across arms. TCZ-SC had a comparable safety profile to TCZ-IV through week 97, except that injection site reactions (ISRs) were more common with TCZ-SC. Safety profiles in patients who switched were similar to those in patients who received continuous TCZ-SC or TCZ-IV treatment. The proportion of patients who developed anti-TCZ antibodies remained low across treatment arms. No association between anti-TCZ antibody development and clinical response or adverse events was observed.

Conclusions: The long-term efficacy and safety of TCZ-SC was maintained and comparable to that of TCZ-IV, except for ISRs. Profiles in patients who switched formulations were comparable to those in patients who received TCZ-IV or TCZ-SC. TCZ-SC provides additional treatment options for patients with RA.

Trial registration number: NCT01194414.

Keywords: DMARDs (biologic); Rheumatoid Arthritis; Treatment.

Figure 1

Study design. All patients continued to receive ≥1 permitted traditional disease-modifying antirheumatic drug at the stable pre-entry dose as prescribed by the treating physician. DB, double-blind; DI, dose interruption; IV, intravenous; OL, open-label; qw, weekly; q4w, every four weeks; R, randomisation; SC, subcutaneous; TCZ, tocilizumab.

Figure 2

Patient disposition over 97 weeks. All patients received ≥1 dose of study drug and were eligible for inclusion in the intent-to-treat (all patients who received ≥1 dose of study drug) and safety (all patients who received ≥1 dose of TCZ and had ≥1 postdose safety assessment) populations. AE, adverse event; IV, intravenous; OL, open-label; qw, weekly; q4w, every 4 weeks; SC, subcutaneous; TCZ, tocilizumab.

Figure 3

Proportion of patients treated with either (A) subcutaneous tocilizumab (TCZ-SC; n=521) or intravenous tocilizumab (TCZ-IV; n=372) as well as (B) patients who switched from TCZ-SC to TCZ-IV (TCZ-SC–IV; n=48) and vice versa (TCZ-IV–SC; n=186) achieving 20%, 50% and 70% improvements per the American College of Rheumatology criteria (ACR20, ACR50 and ACR70), (C) remission based on Disease Activity Score using 28 joints (DAS28 <2.6) and (D) Health Assessment Questionnaire-Disease Index (HAQ-DI) response (HAQ-DI score decreases of ≥0.3) from baseline over 97 weeks (intent-to-treat population). The ns refer to completer analysis. For TCZ-SC and TCZ-IV, this refers to patients who continued on TCZ-SC or TCZ-IV from baseline through the open-label period; patients who switched are not included in this population. If a patient withdrew prior to week 97 but had efficacy measurements between weeks 85 and 96, the patient was still counted for efficacy analysis but not as a patient who completed week 97. qw, weekly; q4w, every four weeks.

Figure 4

Mean (±SD) tocilizumab (TCZ) serum concentration over time (ITT-PK population) in patients treated with either subcutaneous TCZ (TCZ-SC; n=521) or intravenous TCZ (TCZ-IV; n=372) as well as patients who switched from TCZ-SC to TCZ-IV (TCZ-SC–IV; n=48) and vice versa (TCZ-IV–SC; n=186). ITT, intent-to-treat; PK, pharmacokinetic; qw, weekly; q4w, every four weeks.