Evaluation of safety, efficacy and post-cessation efficacy durability of tocilizumab in patients with active rheumatoid arthritis.

To evaluate safety and efficacy of tocilizumab (TCZ) in a post-approval pilot study among selected Iranian patients with moderate to severe rheumatoid arthritis (RA) and inadequate responses to disease-modifying antirheumatic drugs (DMARDs). Twenty-four weeks monitoring of adverse events and efficacy of TCZ plus previously used DMARD(s) and steroids, as well as investigating durability of TCZ effects within a year after the drug cessation. The efficacy end-points included 28-joint Disease Activity Score (DAS28) and an annual change in radiographic Sharp-van der Heijde score (SHS). With no withdrawal from the study due to adverse events (AE) or unsatisfactory responses in the 21 treated patients, the most common drug-related AEs were dermatologic and the most common serious AEs were infectious in origin (all of the latter occurring after the last drug dose). The only case of TCZ dose alteration was due to increased transaminase levels. Changes in lipid and hemoglobin levels were within the expected ranges. At week 24, cumulative frequencies for significant clinical response, low disease activity and remission were 100%, 90.5% and 76.2%, respectively. The mean SHS in both hands showed no significant change a year after the first TCZ dose. Mean DAS28 levels gradually increased through 1 year post-cessation follow-up, with a somewhat slower rate compared to the initial mean DAS28 reduction. In our DMARD-resistant RA patients, TCZ plus DMARD provided a predicted rapid clinical improvement and inhibited structural joint damage, but with some unexpected safety concerns and an expected vanishing of post-cessation efficacy.

Ahmadzadeh A ，Farahmand AN ，Gachkar L 《-》

Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

Abdulkader OAF ，Qushmaq K ，Aljishi F 《-》

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

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). 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. 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. 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. NCT01194414.

Burmester GR ，Rubbert-Roth A ，Cantagrel A ，Hall S ，Leszczynski P ，Feldman D ，Rangaraj MJ ，Roane G ，Ludivico C ，Bao M ，Rowell L ，Davies C ，Mysler EF ... -  《-》

Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.

The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28-erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52. The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde-modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, -0.81 vs -0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group. TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA. ClinicalTrials.gov, number NCT01007435.

Burmester GR ，Rigby WF ，van Vollenhoven RF ，Kay J ，Rubbert-Roth A ，Kelman A ，Dimonaco S ，Mitchell N ... -  《-》

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis.

Kivitz A ，Olech E ，Borofsky MA ，Zazueta B ，Navarro-Sarabia F ，Radominski SC ，Merrill JT ，Pacheco-Tena C ，Pei J ，Nasmyth-Miller C ，Pope JE ... -  《-》