Long-Term Outcome of Ustekinumab Therapy for Behçet's Disease.
Adult
Asthenia
/ chemically induced
Behcet Syndrome
/ drug therapy
Colchicine
/ therapeutic use
Female
Headache
/ chemically induced
Humans
Longitudinal Studies
Male
Middle Aged
Oral Ulcer
/ drug therapy
Prospective Studies
Treatment Failure
Treatment Outcome
Tubulin Modulators
/ therapeutic use
Ustekinumab
/ therapeutic use
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
11
11
2018
accepted:
16
04
2019
pubmed:
23
4
2019
medline:
25
2
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
Oral ulcers, the hallmark lesion of Behçet's disease (BD), can be disabling and resistant to conventional treatment, and there is a need for safe and effective treatment. We undertook this study to investigate the long-term safety and efficacy of ustekinumab therapy for BD-related oral ulcers that are resistant to colchicine. This multicenter, prospective, open-label study included 30 patients who fulfilled the criteria of the International Study Group for BD and who were diagnosed as having active oral ulcers resistant to colchicine. Patients were treated subcutaneously with ustekinumab 90 mg at inclusion, at week 4, and then once every 12 weeks. Each patient was assessed longitudinally for the presence and number of oral ulcers, and median numbers of oral ulcers (with interquartile range [IQR]) were calculated. The primary efficacy end point was the proportion of patients at week 12 who experienced complete response, defined as having no oral ulcers. The median number of oral ulcers per patient during ustekinumab therapy was significantly lower at week 12 compared to baseline (0 [IQR 0-1] versus 2 [IQR 2-3]; P < 0.0001). Complete response was achieved in 60.0% and 88.9% of patients at weeks 12 and 24, respectively. The median Behçet's Syndrome Activity Score (in which higher scores indicate more active disease) was significantly lower at weeks 12 and 24 (17.5 [IQR 10-42.5] and 10 [IQR 8-11], respectively) versus baseline (70 [IQR 50-70]; P < 0.0001). After a median follow-up of 12 months (IQR 6-16 months), 26 patients (86.7%) were still receiving ustekinumab treatment. Reasons for ustekinumab discontinuation included BD flare (n = 3) and side effects (n = 1). Seven patients (23.3%) experienced adverse events, including headaches (n = 4) and asthenia (n = 2), with no serious side effects. Ustekinumab seems to be effective in treating BD-related oral ulcers that are resistant to treatment with colchicine.
Substances chimiques
Tubulin Modulators
0
Ustekinumab
FU77B4U5Z0
Colchicine
SML2Y3J35T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1727-1732Informations de copyright
© 2019, American College of Rheumatology.
Références
Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med 1999;341:1284-91.
Yazici H, Yurdakul S, Hamuryudan V. Behçet disease. Curr Opin Rheumatol 2001;13:18-22.
Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, et al. 2018 update of the EULAR recommendations for the management of Behçet's syndrome. Ann Rheum Dis 2018;77:808-18.
Hatemi G, Melikoglu M, Tunc R, Korkmaz C, Turgut Ozturk B, Mat C, et al. Apremilast for Behçet's syndrome: a phase 2, placebo-controlled study. N Engl J Med 2015;372:1510-8.
Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U. Modulation of CLA, IL-12R, CD40L, and IL-2Rα expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cell Immunol 2007;247:1-11.
Touzot M, Cacoub P, Bodaghi B, Soumelis V, Saadoun D. IFN-α induces IL-10 production and tilt the balance between Th1 and Th17 in Behçet disease. Autoimmun Rev 2015;14:370-5.
Habibagahi Z, Habibagahi M, Heidari M. Raised concentration of soluble form of vascular endothelial cadherin and IL-23 in sera of patients with Behçet's disease. Mod Rheumatol 2010;20:154-9.
Gheita TA, Gamal SM, Shaker I, El Fishawy HS, El Sisi R, Shaker OG, et al. Clinical significance of serum interleukin-23 and A/G gene (rs17375018) polymorphism in Behçets disease: relation to neuro-Behçet, uveitis and disease activity [letter]. Joint Bone Spine 2015;82:213-5.
Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nat Genet 2010;42:698-702.
Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci. Nat Genet 2010;42:703-6.
Mirouse A, Barete S, Monfort JB, Resche-Rigon M, Bouyer AS, Comarmond C, et al. Ustekinumab for Behçet's disease. J Autoimmun 2017;82:41-6.
International Team for the Revision of the International Criteria for Behçet's Disease (ITR-ICBD). The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014;28:338-47.
Yilmaz S, Simsek I, Cinar M, Erdem H, Kose O, Yazici Y, et al. Patient-driven assessment of disease activity in Behçet's syndrome: cross-cultural adaptation, reliability and validity of the Turkish version of the Behçet's Syndrome Activity Score. Clin Exp Rheumatol 2013;31:77-83.
Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008;371:1665-74.
Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, et al. A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology 2008;135:1130-41.
Kopylov U, Afif W, Cohen A, Bitton A, Wild G, Bessissow T, et al. Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn's disease: the McGill experience. J Crohns Colitis 2014;8:1516-22.
Diri E, Mat C, Hamuryudan V, Yurdakul S, Hizli N, Yazici H. Papulopustular skin lesions are seen more frequently in patients with Behçet's syndrome who have arthritis: a controlled and masked study. Ann Rheum Dis 2001;60:1074-6.
Karaca M, Hatemi G, Sut N, Yazici H. The papulopustular lesion/arthritis cluster of Behçet's syndrome also clusters in families. Rheumatology (Oxford) 2012;51:1053-60.
Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013;382:780-9.
Kavanaugh A, Ritchlin C, Rahman P, Puig L, Gottlieb AB, Li S, et al. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis 2014;73:1000-6.
Baerveldt EM, Kappen JH, Thio HB, van Laar JA, van Hagen PM, Prens EP. Successful long-term triple disease control by ustekinumab in a patient with Behçet's disease, psoriasis and hidradenitis suppurativa [letter]. Ann Rheum Dis 2013;72:626-7.
Matsumoto S, Mashima H. Efficacy of ustekinumab against infliximab-induced psoriasis and arthritis associated with Crohn's disease. Biologics 2018;12:69-73.
Deodhar A, Gensler LS, Sieper J, Clark M, Calderon C, Wang Y, et al. Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis. Arthritis Rheumatol 2019;71:258-70.
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007;80:273-90.
Schafer PH, Parton A, Gandhi AK, Capone L, Adams M, Wu L, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010;159:842-55.
Hatemi G, Mahr A, Takeno M, Kim DY, Melikoglu M, Cheng S, et al. OP0082 Apremilast for Behçet's syndrome: a phase III randomised, placebo-controlled, double-blind study (RELIEF) [abstract]. Ann Rheum Dis 2018;77 Suppl 2:91-2.
Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;371:1675-84.