249. IMPROVEMENTS AND CORRELATIONS IN ORAL ULCERS, DISEASE ACTIVITY, AND QOL IN BEHÇET’S SYNDROME PATIENTS TREATED WITH APREMILAST: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

ABSTRACT Objectives Apremilast efficacy and safety was assessed in a prespecified subgroup of Japanese patients with oral ulcers associated with Behçet’s syndrome from a Phase 3 randomized, placebo-controlled, double-blind study of apremilast (RELIEF). Methods The primary end point was area under the curve for number of oral ulcers during the 12-week placebo-controlled phase (AUCWk0–12). Key secondary end points were change from baseline in oral ulcer pain, complete oral ulcer resolution, and measures of disease activity and quality of life (QoL). Results Thirty-nine Japanese patients were randomised (apremilast 30 mg BID: n = 19; placebo: n = 20). Improvements at Week 12 were observed for apremilast vs. placebo in AUCWk0–12 for the number of oral ulcers (115.9 vs. 253.3; nominal P = 0.0168); 57.9% vs. 25.0% achieved complete oral ulcer resolution, 47.4% vs. 0.0% achieved oral ulcer resolution by Week 6 and maintained oral ulcer-free status for ≥6 additional weeks; mean change from baseline in BSAS was −10.5 vs. 0.5. Favourable effects were observed for apremilast vs. placebo in other secondary end points, including QoL. Clinical benefits were sustained over 28 weeks of continued apremilast treatment. Adverse events were consistent with apremilast’s known safety profile. Conclusions Apremilast reduced the number of oral ulcers and overall disease activity in this Japanese subgroup with Behçet’s syndrome.

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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

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Inefficacy of Topical Alpha Interferon in the Treatment of Oral Ulcers of Behçet's Syndrome: a Randomized, Double Blind Trial

Rheumatology ◽

10.1093/rheumatology/30.5.395-a ◽

1991 ◽

Vol 30 (5) ◽

pp. 395-396 ◽

Cited By ~ 30

Author(s):

V. HAMURYUDAN ◽

S. YURDAKUL ◽

F. ROSENKAIMERI ◽

H. YAZICI

Keyword(s):

Alpha Interferon ◽

Behçet’S Syndrome ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial ◽

Behçet's Syndrome ◽

Oral Ulcers ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

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Discordance between patient and physician global assessment of disease activity in Behçet’s syndrome: a multicenter study cohort

Arthritis Research & Therapy ◽

10.1186/s13075-020-02362-1 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Alberto Floris ◽

◽

Gerard Espinosa ◽

Luisa Serpa Pinto ◽

Nikolaos Kougkas ◽

...

Keyword(s):

Disease Activity ◽

Global Assessment ◽

Inactive Disease ◽

Ocular Involvement ◽

Behçet’S Syndrome ◽

Behçet's Syndrome ◽

Patient Reported ◽

Behcet’S Syndrome ◽

Assessment Of Disease Activity ◽

Behcet's Syndrome

Abstract Background To compare the patients’ and physician’s global assessment of disease activity in Behçet’s syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance. Methods A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6–55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet’s syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients’ (PtGA) and physician’s global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA<PGA) discordance using both a more stringent (∆ = ±2) and a less stringent (∆ = ±1) cutoff. Univariate and multivariate logistic regressions were performed. Results Median PtGA and PGA scores were 2.0 (0.3–5.0) and 1.0 (0.0–3.0) cm, respectively. The discordance prevalence varied (from 29.6 to 55.3%) according to the cutoff applied, and the majority (> 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0–2) and 0 (0–1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93–0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93–0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48–23.30, p = 0.012). Conclusions PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient’s health that negatively affect his well-being and the treatment.

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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.

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Behçet’s syndrome

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.191105_update_002 ◽

2010 ◽

pp. 3684-3687

Author(s):

Hasan Yazici ◽

Sebahattin Yurdakul ◽

Izzet Fresko

Keyword(s):

Clinical Laboratory ◽

Central Nervous System Involvement ◽

Arterial Occlusion ◽

Inflammatory Disorder ◽

Behçet’S Syndrome ◽

Laboratory Findings ◽

Behçet's Syndrome ◽

Oral Ulcers ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

Behçet’s syndrome is an inflammatory disorder of unknown aetiology that involves arteries and veins of all sizes. Most cases are from the countries around the Mediterranean basin, the Middle East and east Asia, with the highest prevalence in Turkey. Clinical features—the disease typically presents in the second and third decades with recurrent oral ulcers (98% of cases), genital ulcers (85%), acneiform lesions (85%), pathergy reaction (60% in some countries), erythema nodosum (50%), uveitis (50%), arthritis (50%), thrombophlebitis (30%), and less commonly with arterial occlusion/aneurysm, central nervous system involvement or gastrointestinal lesions. A relapsing/remitting course is usual. Disease is more severe and mortality is higher in men. The diagnosis is clinical, laboratory findings are nonspecific and there is no specific diagnostic test for Behçet’s syndrome....

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