Efficacy and safety of secukinumab in Japanese patients with active ankylosing spondylitis: 24-week results from an open-label phase 3 study (MEASURE 2-J).

Objective: Secukinumab, a fully human monoclonal antibody that neutralizes interleukin-17A, improved the signs and symptoms of ankylosing spondylitis (AS) in three Phase 3 global studies (MEASURE 1, 2, and 3). Here, we describe the efficacy and safety results through Week 24 of a study of secukinumab in Japanese patients with active AS.Methods: In this multicenter, open-label, single arm, 52-week study, 30 AS patients self-administered secukinumab 150 mg subcutaneously at baseline, Weeks 1, 2, 3, and 4, and every 4 weeks thereafter. The primary efficacy endpoint was ASAS 20 response at Week 16. Overall safety and tolerability were assessed beyond Week 24 up to the data reporting cut-off date.Results: The ASAS 20 response rate was 70% (21/30) at Week 16, which was sustained to Week 24. Secukinumab was effective in various clinical outcomes including patient's global assessment of disease activity, spinal pain, nocturnal pain, physical function, spinal mobility, and CRP level. Comparable ASAS 20 and 40 responses were observed regardless of previous anti-TNF therapy. Secukinumab was well-tolerated with a safety profile consistent with previous reports.Conclusion: Secukinumab 150 mg provided sustained improvement in the signs and symptoms of Japanese AS patients through 24 weeks, with no new or unexpected safety signals.

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch.

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate-to-severe psoriasis. In this multicenter, open-label, phase IV study, 34 patients with moderate-to-severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end-point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end-point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.

Altered mechanical properties in smooth muscle of mice with a mutated calponin locus.

The mechanical properties of smooth muscles in aorta and vas deferens were studied in mice with a mutated basic calponin locus to learn the physiological function of calponin. The intact smooth muscles were stimulated with high KCl and the force development was compared between calponin deficient (knockout, KO) mice and wild type (WT) ones. The isometric force induced by various concentrations of high KCl was lower in KO than in WT both in aorta and in vas deferens. The length-force relations were compared between KO and WT. The active isometric force in KO was significantly lower at most muscle lengths examined than in WT without the change in resting force both in aorta and in vas deferens. In vas deferens, the rate of force development after quick release in length at the peak force was significantly faster in KO than in WT. The above results show that the force development is lower and the rate of cross-bridge cycle is faster in KO mice than in WT ones, suggesting that calponin plays basic roles in the control of the contraction of smooth muscle.