AB0481 EFFICACY OF APREMILAST FOR THE TREATMENT OF GENITAL ULCERS ASSOCIATED WITH ACTIVE BEHÇET’S SYNDROME: A COMBINED ANALYSIS OF TWO RANDOMIZED CONTROLLED TRIALS

Background:Behçet’s syndrome is a chronic, multi-system inflammatory disorder characterized by painful, recurrent oral ulcers (OU) and genital ulcers (GU).1The GU associated with Behçet’s syndrome can contribute to difficulties with sexual activity, walking, and sitting2; may cause scarring1; and may impair quality of life.1,2Apremilast (APR), an oral phosphodiesterase 4 inhibitor, has demonstrated efficacy in the treatment of the OU associated with Behçet’s syndrome in the phase III, randomized RELIEF study (BCT-002).3Objectives:To describe the efficacy of APR for the treatment of GU associated with active Behçet’s syndrome in the RELIEF study and in a pooled data analysis of RELIEF and the phase II study.Methods:Adult patients (≥18 years of age) with active Behçet’s syndrome and ≥3 OU at randomization or ≥2 OU at screening and randomization, without active major organ involvement, were randomized (1:1) to APR 30 mg twice daily or placebo (PBO). In RELIEF, clinical improvement in GU was assessed by evaluating the time to the first GU recurrence after loss of complete response, the mean number of GU in patients without GU at baseline, and the proportion of patients who were GU-free (complete response) at Week 12 (regardless of baseline GU status). A pooled analysis of patients in RELIEF and a randomized, phase II study4were conducted to assess achievement of GU complete response in patients with GU at baseline. In patients with GU complete response before Week 12, the median time to the first GU recurrence after loss of complete response was based on Kaplan-Meier estimates. The mean number of GU was summarized descriptively using data as observed. Between-group differences in the proportion of patients who were GU-free at Week 12 were analyzed by Cochran-Mantel-Haenszel test using non-responder imputation to handle missing data. Statistical tests were 2 sided (α=0.05).Results:A total of 207 patients were randomized and received ≥1 dose of study medication (APR: n=104; PBO: n=103). In all, 17 patients in the APR group and 17 in the PBO group had GU at baseline, with mean GU counts of 2.9 (APR) and 2.6 (PBO). Among patients with GU at baseline in RELIEF, 12/17 (70.6% [APR]) and 7/17 (41.2% [PBO]) achieved GU complete response at Week 12 (P=0.110). The median time to first GU recurrence in these patients occurred earlier with PBO (6.1 weeks) vs. APR (not calculable). In the pooled analysis of RELIEF and the phase II study, a significantly greater proportion of patients with GU at baseline achieved GU complete response at Week 12 with APR vs. PBO (21/27 [77.8%] vs. 9/23 [39.1%];P=0.011) (Figure 1). The proportion of patients who were GU-free was significantly greater with APR (92/104 [88.5%]) vs. PBO (72/101 [71.3%]), regardless of baseline number of GU (P=0.002) (Figure 2).Conclusion:The number of patients with GU was low, but the totality of the data shows a favorable trend in the treatment effect of APR on GU. Greater proportions of APR-treated patients were GU-free at Week 12 vs. patients receiving PBO, and the time to the first GU recurrence occurred earlier with PBO vs. APR.References:[1]Kokturk A. Patholog Res Int. 2012;2012:690390. 2. Senusi A, et al. Orphanet J Rare Dis. 2015;10:117. 3. Hatemi G, et al. N Engl J Med. 2019;381:1918-1928. 4. Hatemi G, et al. N Engl J Med. 2015;372:1510-1518.Disclosure of Interests:Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker, Alfred Mahr Consultant of: Celgene, Speakers bureau: Roche, Chugai, Mitsuhiro Takeno Speakers bureau: Esai, Tanabe-Mitsubishi – speaker; Celgene Corporation – advisory board, Doyoung Kim: None declared, Melike Melikoglu: None declared, Sue Cheng Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Shannon McCue Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Sven Richter Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Michele Brunori Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Maria Paris Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Mindy Chen Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of the conduct, Yusuf Yazici Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant, Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant

Download Full-text

OP0028 EFFICACY OF APREMILAST FOR THE PAIN OF ORAL ULCERS ASSOCIATED WITH ACTIVE BEHÇET’S SYNDROME: 12-WEEK RESULTS FROM THE RANDOMIZED, PHASE III RELIEF STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2908 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 20.2-21

Author(s):

G. Hatemi ◽

A. Mahr ◽

M. Takeno ◽

D. Kim ◽

M. Melikoglu ◽

...

Keyword(s):

Phase Iii ◽

Controlled Study ◽

Behçet’S Syndrome ◽

Research Support ◽

Behçet's Syndrome ◽

Oral Ulcers ◽

Behcet’S Syndrome ◽

Vas Scores ◽

The Mean ◽

Behcet's Syndrome

Background:Oral ulcers (OU) associated with Behçet’s syndrome are often painful, may interfere with the ability to eat and can negatively affect quality of life.1,2Apremilast (APR), an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in the treatment of OU associated with Behçet’s syndrome in a phase III, multicenter, randomized, double-blind, placebo (PBO)-controlled study (RELIEF; BCT-002).3Objectives:To describe the efficacy of APR treatment in improving OU pain associated with Behçet’s syndrome in RELIEF.Methods:Patients were randomized (1:1) to APR 30 mg twice daily (APR 30 BID) or PBO twice daily for a 12-week PBO-controlled phase, followed by a 52-week active treatment extension. Eligible patients were ≥18 years of age and had active Behçet’s syndrome with ≥3 OU at randomization or ≥2 OU at screening and randomization and without active major organ involvement. Clinical improvement in OU was evaluated by the area under the curve for the number of OU through Week 12 (AUCWk0-12; primary efficacy endpoint) and by assessments of OU number. Patient-reported OU pain was evaluated by the 100-mm visual analogue scale (VAS). The statistical tests were 2-sided (α=0.05). The proportions of patients achieving the minimal clinically important difference (MCID) and higher rates of improvement, defined as ≥10-mm,4≥30-mm (3-fold MCID), ≥50-mm (5-fold MCID) improvements in OU pain VAS scores, respectively, were analyzed through Week 12. An ANCOVA model was used to analyze the primary endpoint and assessments of OU number and OU pain (VAS). The proportion of patients achieving improvement in OU pain VAS scores at Week 12 were summarized descriptively.Results:A total of 207 patients were randomized and received ≥1 dose of study medication (APR: n=104; PBO: n=103). At baseline, the mean (SD) number of OU was 4.2 (3.7) in the APR 30 BID group and 3.9 (2.7) in the PBO group, and the mean (SD) OU pain VAS scores were 61.2 (27.6) and 60.8 (26.9), respectively. At Week 12, significantly greater improvements were observed with APR 30 BID vs. PBO in AUCWk0-12(least-squares [LS] mean [SE]: 129.5 [15.9] vs. 222.1 [15.9];P<0.0001), number of OU (LS mean [SE]: 1.1 [0.2] vs. 2.0 [0.3];P=0.0003) and OU pain VAS scores (LS mean [SE] change from baseline: −40.7 [3.3] vs. −15.9 [3.3];P<0.0001). The proportion of patients who achieved the MCID of ≥10-mm improvement in OU pain VAS scores at Week 12 was greater with APR 30 BID vs. PBO; this pattern was also observed for the higher 3- and 5-fold improvements in MCID (Figure 1). Greater proportions of APR 30 BID vs. PBO patients achieved ≥10-mm and ≥30-mm improvements in OU pain VAS scores over 12 weeks. Notably, greater achievement of ≥50-mm improvement in OU pain VAS scores was observed with APR 30 BID vs. PBO as early as Week 1 and maintained up to Week 12 (Figure 2).Conclusion:For patients with active Behçet’s syndrome, APR 30 BID provided significantly greater improvements vs. PBO in OU number and OU pain at Week 12, including the greater proportion of patients achieving MCID and 3- and 5-fold MCID of OU pain in the APR 30 BID group vs. the PBO group. These results indicate a clinically meaningful treatment effect of APR 30 BID on the OU associated with Behçet’s syndrome.References:[1]Kokturk A.Patholog Res Int. 2012;2012:690390.[2]Hatemi G, et al.Ann Rheum Dis. 2008;67:1656-1662.[3]Hatemi G, et al.N Engl J Med. 2019;381:1918-1928. 4. Dworkin RH, et al.J Pain. 2008;9:105-121.Disclosure of Interests:Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker, Alfred Mahr Consultant of: Celgene, Speakers bureau: Roche, Chugai, Mitsuhiro Takeno Speakers bureau: Esai, Tanabe-Mitsubishi – speaker; Celgene Corporation – advisory board, Doyoung Kim: None declared, Melike Melikoglu: None declared, Sue Cheng Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Shannon McCue Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Sven Richter Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Michele Brunori Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Maria Paris Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Mindy Chen Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of the conduct, Yusuf Yazici Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant, Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant

Download Full-text

Serum Levels of Interleukin-36 Alpha and Interleukin-36 Receptor Antagonist In Behcet’s Syndrome

Aktuelle Rheumatologie ◽

10.1055/a-1550-2069 ◽

2021 ◽

Author(s):

Pelin Ünsal ◽

Pamir Çerçi ◽

Şükrü Alper Açıkgöz ◽

Göksal Keskin ◽

Ümit Ölmez

Keyword(s):

Central Nervous System Involvement ◽

Serum Levels ◽

Behçet’S Syndrome ◽

Behçet's Syndrome ◽

Oral Ulcers ◽

Group A ◽

Behcet’S Syndrome ◽

The Mean ◽

Clinically Significant ◽

Behcet's Syndrome

Abstract Background Behcet’s syndrome (BS) is a systemic vasculitic disorder. This study aimed to investigate the levels of serum IL-36α and IL-36Ra in patients with BS. Material and Methods A total of 80 subjects (60 BS patients and 20 healthy controls [HC]) were included. Results The median IL-36α level was 0.11 ng/ml in the BS group and 0.09 ng/ml in the HC group (p=0.058). The mean IL-36Ra level was 13.62 pg/ml in the BS group and 13.26 pg/ml in the HC group (p=0.348). Serum IL-36Ra levels of the active group were significantly higher (p=0.037). Patients with oral ulcers and central nervous system involvement had higher serum IL36Ra levels. In the BS group, a positive correlation was found between serum IL-36Ra and CRP. In a multivariate analysis, the IL-36Ra level (OR=1.067; 95% CI=1.001–1.137; p=0.045) was independently associated with disease activity. Conclusion According to these findings, it is not clear whether such a slight difference is clinically significant, but they suggest that the IL-36 cytokine family may play a role in the course of the disease.

Download Full-text

FRI0331 Apremilast for the treatment of behçet’s syndrome: a phase ii randomized, placebo-controlled, double-blind study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-eular.1458 ◽

2013 ◽

Vol 72 (Suppl 3) ◽

pp. A486.2-A486 ◽

Cited By ~ 1

Author(s):

G. Hatemi ◽

M. Melikoglu ◽

R. Tunc ◽

C. Korkmaz ◽

B. T. Ozturk ◽

...

Keyword(s):

Phase Ii ◽

Blind Study ◽

Double Blind Study ◽

Behçet’S Syndrome ◽

Double Blind ◽

Behçet's Syndrome ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

Download Full-text

Long-term effectiveness and safety of secukinumab for treatment of refractory mucosal and articular Behçet’s phenotype: a multicentre study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217108 ◽

2020 ◽

Vol 79 (8) ◽

pp. 1098-1104 ◽

Cited By ~ 3

Author(s):

Filippo Fagni ◽

Alessandra Bettiol ◽

Rosaria Talarico ◽

Giuseppe Lopalco ◽

Elena Silvestri ◽

...

Keyword(s):

Complete Response ◽

Term Treatment ◽

Behçet’S Syndrome ◽

Biologic Treatment ◽

Behçet's Syndrome ◽

Long Term Treatment ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

ObjectiveTo evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet’s phenotype resistant to conventional and biologic treatment.MethodsA multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet’s syndrome fulfilling the International Criteria for Behçet’s Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations.ResultsAt 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.ConclusionsOur study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet’s syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.

Download Full-text

Apremilast in Refractory Behçet’s Syndrome: A Multicenter Observational Study

Frontiers in Immunology ◽

10.3389/fimmu.2020.626792 ◽

2021 ◽

Vol 11 ◽

Author(s):

Matheus Vieira ◽

Solène Buffier ◽

Mathieu Vautier ◽

Alexandre Le Joncour ◽

Yvan Jamilloux ◽

...

Keyword(s):

Adverse Events ◽

Complete Response ◽

Joint Disease ◽

Behçet’S Syndrome ◽

Multicenter Observational Study ◽

Entire Cohort ◽

Behçet's Syndrome ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

ObjectiveMucocutaneous and joint disorders are the most common manifestations in Behçet’s syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS.MethodsFrench nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero.ResultsAt inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet’s syndrome activity score significantly decreased during study period [50 (40–60) vs. 20 (0–40); p <0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%).ConclusionApremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.

Download Full-text