scholarly journals Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial

2020 ◽  
Vol 79 (10) ◽  
pp. 1362-1369 ◽  
Author(s):  
Seza Ozen ◽  
Eldad Ben-Cherit ◽  
Ivan Foeldvari ◽  
Gil Amarilyo ◽  
Huri Ozdogan ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Disease Activity ◽  
Phase Iii ◽  
Physician Global Assessment ◽  
Efficacy And Safety ◽  
Open Label ◽  
Amyloid A ◽  
Term Efficacy ◽  
Mediterranean Fever

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab to treat patients with colchicine-resistant familial Mediterranean fever (crFMF) during Epoch 4 (weeks 41 to 113) of the CLUSTER study.MethodsPatients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. We evaluated disease activity every 8 weeks using the physician global assessment (PGA) of disease activity, counting the number of flares, and measuring concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was studied by determination and classification of observed adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of less than 2700 mg, or equal or more than 2700 mg.ResultsOf the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares per year reported at baseline. PGA scores indicated no disease activity for the majority of patients throughout the study. Median CRP concentrations were always lower than 10 mg/L, while median SAA concentrations remained over the limit of normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were reported.ConclusioncrFMF patients treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety concerns reported.

scholarly journals OP0272 LONG-TERM EFFICACY AND SAFETY OF CANAKINUMAB IN PATIENTS WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER: RESULTS FROM THE RANDOMISED PHASE 3 CLUSTER TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 169.2-170
Author(s):  
S. Özen ◽  
E. Ben-Chetrit ◽  
I. Foeldvari ◽  
G. Amarilyo ◽  
H. Ozdogan ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Disease Activity ◽  
Cumulative Dose ◽  
Current Therapy ◽  
Efficacy And Safety ◽  
Cluster Trial ◽  
Research Support ◽  
Term Efficacy ◽  
Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with mutations in theMEFVgene. Colchicine is the cornerstone of current therapy for FMF; however, a subset of patients are resistant or intolerant to it. Previously published results from the CLUSTER trial [NCT02059291] demonstrated that canakinumab, a fully human anti-interleukin-1β monoclonal antibody, was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever (crFMF).1Objectives:To evaluate the long-term efficacy and safety of canakinumab to treat patients with crFMF during Epoch 4 of the CLUSTER study.Methods:Patients with active crFMF (baseline flare) were enrolled in the CLUSTER study. During Epoch 4 (weeks 40 to 113), patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks (q4w or q8w). Patients started Epoch 4 on the same regimen that they were receiving at the end of Epoch 3, and stepwise up-titration of canakinumab was allowed in patients who experienced a flare, to a maximum dose of 300 mg q4w. We evaluated disease activity every 8 weeks using the physician global assessment of disease activity (PGA), counting the number of flares (defined as PGA ≥2 and CRP >30 mg/L), and measuring serum concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was assessed by the determination and classification of adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of canakinumab lower than 2700 mg, or equal or higher than 2700 mg.Results:Of the 61 patients with active crFMF who started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one single flare, as compared with a median of 17.5 flares per year reported at baseline. The incidence of flares was similar in the two cumulative dose groups. PGA scores indicated no disease activity for the majority of patients throughout the study, in both cumulative dose groups. 23/57 (40%) of patients remained in the lower dosing group (150 mg q8w) until study end, whereas 9/57 (16%) required the highest dose allowed (300 mg q4w). Patients with higher body weight had an increased probability to require up-titration of canakinumab to control disease activity. Median CRP concentrations were lower than 10 mg/L at every time point in both cumulative dose groups, while median SAA concentrations remained in the 16-70 mg/L range, and were higher in the group receiving ≥2700 mg canakinumab (Figure 1). No opportunistic infections, renal disease caused by amyloidosis, new or unexpected AEs were reported.Figure 1.SAA and CRP blood levels in Epoch 4 of the CLUSTER study, in two subgroups of patients treated with a cumulative dose of canakinumab <2700 mg or ≥2700 mgConclusion:Patients with crFMF treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety signals reported.References:[1]De Benedetti F et al.N Engl J Med2018;378:1908–19.Disclosure of Interests:Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis, Eldad Ben-Chetrit Speakers bureau: Novartis, Ivan Foeldvari Consultant of: Novartis, Gil Amarilyo Grant/research support from: Novartis, Speakers bureau: Novartis, Huri Ozdogan: None declared, Steven Vanderschueren: None declared, Katherine Marzan Grant/research support from: Novartis, J Michelle Kahlenberg Grant/research support from: Celgene, BMS, Consultant of: Eli Lilly, AstraZeneca, BMS, Boehringer Ingleheim, Elise Dekker Employee of: Novartis, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi, Isabelle Koné-Paut Consultant of: Novartis, Chugai, Pfizer, LFB, AbbVie, Novimmune, SOBI

scholarly journals Long-Term Efficacy and Safety of Liquid Abobotulinumtoxina Formulation for Moderate-To-Severe Glabellar Lines: A Phase III, Double-Blind, Randomized, Placebo-Controlled and Open-Label Study

2021 ◽  
Author(s):  
Philippe Kestemont ◽  
Said Hilton ◽  
Bill Andriopoulos ◽  
Inna Prygova ◽  
Catherine Thompson ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Neutralizing Antibodies ◽  
Well Being ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Patient Reported

Abstract Background A ready-to-use liquid formulation of abobotulinumtoxinA (aboBoNT-A solution) has been developed. Objectives To assess long-term efficacy and safety of aboBoNT-A solution for glabellar lines (GL) treatment. Methods Multicenter, multinational, Phase III study (NCT02493946), with randomized double-blind placebo-controlled (DBPC; 2:1 aboBoNT-A solution 50 U: placebo) and open-label (OL; 4 cycles aboBoNT-A solution) periods; additional patients were recruited into the OL period. Patients were 18-65 years old; BoNT-naïve; dissatisfied/very dissatisfied with moderate/severe GLs at maximum frown. Investigator’s live assessment (ILA; primary endpoint)/subject’s self-assessment (SSA) of GL severity at maximum frown, patient satisfaction with GL appearance, and FACE-Q patient-reported scales (facial appearance overall, psychological well-being, aging) were assessed. Adverse events (AEs) were monitored. Analyses were performed on DBPC and long-term analysis (LTA; all patients receiving ≥ aboBoNT-A solution injection) populations. Results Mean ages of patients were 46.6–47.8 years, and 89.1–91.3% were female, across DBPC (N=190 [n=126 aboBoNT-A solution, n=64 placebo]) and LTA (N=595) populations. Responder rates for ILA, SSA and patient satisfaction were consistent at Day 29 post-injection across repeat LTA cycles (82.2–87.8%, 62.8–80.6% and 72.2–87.8%, respectively), with statistically significantly higher responder rates versus placebo (DBPC cycle; 81.6% versus 0.8%, 68.1% versus 2.3% and 83.1% versus 5.7%, respectively; all p&lt;0.0001). Consistent improvements on FACE-Q scales occurred with repeat cycles (aboBoNT-A solution versus placebo, p&lt;0.0001 [DBPC cycle]). No new or unexpected AEs, or neutralizing antibodies were observed. Conclusions Results support long-term efficacy and safety of aboBoNT-A solution, and its superiority over placebo, for GL treatment in adults.

scholarly journals A Randomized, Double-Blind, Placebo-Controlled Phase III Trial On The Efficacy and Safety of Tocilizumab in Patients With Colchicine-Resistant or -Intolerant Familial Mediterranean Fever

2021 ◽  
Author(s):  
Tomohiro Koga ◽  
Shuntaro Sato ◽  
Naoko Hagimori ◽  
Hiroshi Yamamoto ◽  
Masataka Ishimura ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Mediterranean Fever ◽  
Accompanying Symptoms ◽  
Fever Attacks ◽  
Serum Crp

Abstract Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

scholarly journals Long-term efficacy and safety of once-monthly Risperidone ISM® in the treatment of schizophrenia: Results from a 12-month open-label extension study

2022 ◽  
Vol 239 ◽  
pp. 83-91
Author(s):  
Yuriy Filts ◽  
Robert E. Litman ◽  
Javier Martínez ◽  
Lourdes Anta ◽  
Dieter Naber ◽  
...  
Keyword(s):  
Extension Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Term Efficacy ◽  
Open Label Extension
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