Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

BACKGROUND: Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU. OBJECTIVE: We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. METHODS: In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks. RESULTS: Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively. CONCLUSIONS: Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

Secukinumab is Superior to Ustekinumab in Clearing Skin in Patients with Moderate to Severe Plaque Psoriasis (16-Week CLARITY Results).

INTRODUCTION: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab. METHODS: In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized. RESULTS: Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%). CONCLUSION: The results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov Identifier, NCT02826603. FUNDING: Novartis Pharma AG, Basel, Switzerland.

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study.

BACKGROUND: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis. OBJECTIVE: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. METHODS: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. RESULTS: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. LIMITATIONS: There was no placebo arm. CONCLUSION: In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile.

Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from GESTURE, a randomized controlled trial.

BACKGROUND: Plaque psoriasis affecting palms and soles is disabling and often resistant to treatment. OBJECTIVE: Evaluate the efficacy and safety of secukinumab, an anti-interleukin 17A antibody, in subjects with palmoplantar psoriasis. METHODS: In this double-blinded, randomized controlled trial, 205 subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The primary endpoint was Palmoplantar Investigator's Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16. RESULTS: At week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the percentage achieved with placebo (1.5%, P < .001). Palmoplantar Psoriasis Area and Severity Index (ppPASI) was significantly reduced with secukinumab 300 mg (-54.5%) and 150 mg (-35.3%) compared with placebo (-4.0%, P < .001). Dermatology Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups were also significantly higher compared with placebo at week 16 (P < .01) and pain and function of palms and soles was markedly improved with secukinumab as measured by the palmoplantar Quality-of-Life Instrument. Secukinumab 300 mg consistently showed the best outcomes. The safety profile was favorable and similar to previous studies. LIMITATIONS: Lack of active comparator. CONCLUSION: In GESTURE, the largest randomized controlled trial in palmoplantar psoriasis, secukinumab demonstrated the greatest efficacy to date for treating difficult-to-treat psoriasis.

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study). OBJECTIVE: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab. METHODS: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16. RESULTS: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies. LIMITATIONS: The study was not placebo-controlled and of short-term duration. CONCLUSIONS: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.

One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To evaluate the longer-term safety and efficacy of secukinumab, a fully human monoclonal antiinterleukin-17A antibody, in patients with rheumatoid arthritis. METHODS: In this 52-week, double-blind, placebo-controlled (up to Week 20) study (NCT00928512), patients responding inadequately to disease-modifying antirheumatic drugs (DMARD) or biologics were randomized to receive monthly subcutaneous injections of secukinumab (25, 75, 150, or 300 mg), or placebo. The efficacy and safety results up to Week 20 have been reported previously. Here, efficacy results from Week 20 to 52 and safety results from Week 20 to 60 are presented. RESULTS: Of 237 patients randomized, 174 (73.4%) completed the study. Patients with improved American College of Rheumatology (ACR) and 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP) responses at Week 16 sustained their responses through Week 52. In patients taking 150 mg of secukinumab, responses were improved through Week 52 (ACR50: Week 16 = 45%, Week 52 = 55%; DAS28-CRP ≤ 2.6: Week 16 = 25%, Week 52 = 40%). The rate of adverse events (AE) from weeks 20 to 60 was 64.8%, with most AE being mild to moderate in severity. The overall rate of infections was 31.9%, most being mild. The most predominant infection was nasopharyngitis, and was not associated with dose or concurrent neutropenia. Serious AE were reported in 21 patients (8.9%). There were 3 reports of malignancies (ovarian, lung, basal cell), and no deaths between weeks 20 and 60. CONCLUSION: Patients with active RA who failed to respond to DMARD and other biologics showed an improvement after longterm treatment with 150 mg of secukinumab. The frequency of AE remained stable over time and secukinumab had a consistent safety profile over 60 weeks.

Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study.

OBJECTIVE: To assess the safety and efficacy of secukinumab, a fully human monoclonal anti-interleukin-17A antibody, in patients with rheumatoid arthritis (RA). METHODS: Patients (n=237) with inadequate response to methotrexate were randomly assigned to receive monthly subcutaneous injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. The primary endpoint was the American College of Rheumatology 20% response (ACR20) at week 16. RESULTS: Demographics and baseline characteristics were comparable across all treatment groups. The primary efficacy endpoint was not achieved: the proportion of ACR20 responders at week 16 with secukinumab 25-300 mg was 36.0-53.7% versus placebo (34%). Disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) was a secondary endpoint and clinically relevant decreases with secukinumab 75-300 mg were reported versus placebo. Serum high sensitivity CRP levels at week 16 were significantly reduced with secukinumab 75 mg, 150 mg and 300 mg doses versus placebo. The safety profile of secukinumab was consistent with that seen with other biological agents. Most adverse events (AE) were mild to moderate in severity. Infections were slightly more frequent with secukinumab than placebo. Six serious AE were reported: secukinumab 75 mg (one), secukinumab 300 mg (four) and placebo (one). CONCLUSIONS: ACR20 response rates differed between secukinumab 75 mg, 150 mg and 300 mg doses and placebo; however, the primary efficacy endpoint was not achieved. Greater decreases in DAS28 were observed with secukinumab 75 mg, 150 mg and 300 mg than placebo. There were no unexpected safety signals and no specific organ-related toxicities. Further trials with secukinumab in the treatment of RA are warranted.