ACR Boston 2014 | Daily Highlights

A 2-Week Single-Blind, Randomized, 3-Arm Proof of Concept Study of the Effects of Secukinumab (anti-IL17 mAb), Canakinumab (anti-IL-1 b mAb), or Corticosteroids on Initial Disease Activity Scores in Patients with PMR, Followed By an Open-Label Extension to Assess Safety and Effect Duration

Abstract: 885
Presenter: Eric L. Matteson
Co-Authors: Bhaskar Dasgupta, Wolfgang A. Schmidt, Carlo Salvarani, Nagui Gendi, Mauro Galeazzi, Sylvie Stitah, Yue Li, Marie-Anne Valentin, Bolan Linghu and Stephen J. Oliver

Background:
To assess the effects of a single dose of secukinumab or canakinumab in patients with new onset, untreated polymyalgia rheumatica (PMR).

Methods:
In this single-blinded, double-dummy, randomized, active-controlled, parallel-group study, patients with PMR of >1 week duration were randomized 1:1:1 to receive single dose (3 mg/kg/body weight) of either secukinumab or canakinumab, or daily oral prednisone (PRED) at 20 mg a day. The primary endpoint was efficacy after 2 weeks, assessed by the PMR activity score (PMR-AS components: CRP, morning stiffness, ability to elevate arms; 100 mm VAS assessments for patient pain and physician global). Complete response was defined as >70% reduction in patient global assessment VAS compared with baseline, morning stiffness <30 min, and CRP <1.0 mg/dl. Partial response was defined as >50% reduction in patient global assessment VAS compared with baseline and morning stiffness <60 min. Patients treated with biologics failing to achieve criteria for either complete or partial response by Day 15 initiated treatment with PRED 20 mg/day. All patients receiving PRED underwent a scheduled taper after 2 weeks treatment. Patients were followed up to 154 days for safety and duration of treatment effects. Serum levels of IL-6 and VEGF were measured by ELISA.

Results:
16 patients (11 females) were randomized (secukinumab, n=6, mean baseline PMR-AS 46.6; canakinumab, n=5, mean PMR-AS 54.3; PRED n=5, mean baseline PMR-AS 37.5). The primary endpoint was assessed in 13 patients (secukinumab, 6; canakinumab, 3; PRED, 4). PMR-AS reductions from baseline were seen in all patients at day 15: secukinumab =52%; canakinumab =65%; PRED 92%. By Day 15 no biologic-treated patients achieved complete response and only 1 patient in each biologic group achieved a partial response, whereas 1 patient in the PRED arm had complete response and 3 patients had partial responses. CRP reductions were most rapid in the PRED group and more consistent in patients treated with either PRED or secukinumab. In patients treated with PRED, rapid reductions were observed in mean VAS for physician global assessment and patients' assessment of pain compared to only moderate or minimal effects in the secukinumab and canakinumab groups, respectively. PRED induced a rapid and consistent decrease in IL-6 while no consistent effects were noted in patients treated with biologics. Secukinumab induced rapid and consistent decreases in VEGF levels that were not observed in the other two groups. Patients in secukinumab (n=4) and canakinumab (n=3) groups who required switch to PRED with subsequent taper had a 40% and 35% lower monthly average steroid use, respectively, compared to the PRED group (n=4) that had not been exposed to a biologic. All three study treatments were well-tolerated without SAEs or increased infections noted.

Conclusions:
In this study PMR-AS reduced more rapidly by Day 15 in prednisone-treated patients than in patients receiving secukinumab or canakinumab. Patients receiving biologics followed by prednisone had overall lower cumulative steroid doses. The therapeutic effects of secukinumab and canakinumab in PMR remains uncertain and deserves further study.

Disclosure of Interest:
E. L. Matteson, Novartis Pharma AG, 2; B. Dasgupta, Novartis Pharma AG, 2; W. A. Schmidt, Novartis Pharma AG, 2, Mundipharma, 2; C. Salvarani, Novartis Pharma AG, 2; N. Gendi, Novartis Pharma AG, 2, Roche Pharma AG, 2, UCB Pharma, 2; M. Galeazzi, None; S. Stitah, Novartis Pharma AG, 3; Y. Li, Novartis Pharma AG, 3; M. A. Valentin, Novartis Pharma AG, 3; B. Linghu, Novartis Pharma AG, 3; S. J. Oliver, Novartis Pharma AG, 1, Novartis Pharma AG, 3.

Comment:
This small and short term randomized trial shows that classical prednisone treatment more rapidly reduced inflammatory activity in polymyalgia rheumatic (PMR) within the first two weeks compared to biologics such as secukinumab (anti-IL17 mAb) or canakinumab (anti-IL-1b). Because there are no data provided on repeated application of both biologics, their overall utility can still not be valued against classical steroid treatment. However, there is some promising hint on the initial role of biological treatment in PMR in so far that patients receiving biologics followed by prednisone had overall lower cumulative steroid doses during the follow up period of up to 154 days.

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