Apremilast in Refractory Oral and/or Genital Ulcers in Behçet’s Disease. Multicenter Study of 37 Cases

Belén Atienza-Mateo¹, José Luis Martín-Varillas¹, Javier Loricera², Genaro Graña Gil³, Gerard Espinosa⁴, Clara Moriano Morales⁵, Trinidad Pérez-Sandoval⁶, Manuel Martín-Martínez⁶, Elvira Díez⁶, Maria Dolores Garcia Armario⁷, Ivan Castellví⁸, Francisca Sivera⁹, Jaime Calvo-Alén¹⁰, Isabel de la Morena¹¹, Francisco Ortiz-Sanjuán¹², José Andrés Román-Ivorra¹³, Ana Pérez Gómez¹⁴, Sergi Heredia¹⁵, Carolina Díez¹⁶, J Alegre¹⁷, Amparo Ybáñez¹⁷, Javier Narváez¹⁸, Ana Turrión Nieves¹⁹, Susana Romero-Yuste²⁰, Alejandro Olivé-Marqués²¹, Águeda Prior²², Esperanza Martínez⁷, Ignasi Figueras²³, Pilar Trénor²⁴, Carmen Gonzalez Vela²⁵, Diana Prieto Peña²⁶, Monica Calderón Goercke²⁶, José Luis Hernández², Miguel Angel González-Gay¹ and Ricardo Blanco¹, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ²Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ³Rheumatology Division, Complejo Hospitalario Universitario A Coruña. Spain, La Coruña, Spain, ⁴Department of Autoimmune Diseases, Hospital Clinic. Barcelona. Spain, Barcelona, Spain, ⁵Rheumatology, Complejo Asistencial Universitario de León. León. Spain, León, Spain, ⁶Rheumatology, Hospital Universitario de León. Spain, León, Spain, ⁷Rheumatology and Dermatology, Hospital Lluís Alcanyís. Valencia. Spain, Valencia, Spain, ⁸Rheumatology, Hospital Universitari de la Santa Creu i Sant Pau. Barcelona. Spain, Barcelona, Spain, ⁹Rheumatology, Hospital General Universitario de Elda. Comunidad Valenciana. Spain, Elda, Spain, ¹⁰Rheumatology Department, Hospital Universitario Araba. Vitoria-Gasteiz, Alava, Spain, ¹¹Hospital General Universitario de Valencia. Spain, Valencia, Spain, ¹²Rheumatology, Hospital La Fe. Valencia. Spain, Valencia, Spain, ¹³Hospital La Fe. Valencia. Spain, Valencia, Spain, ¹⁴Rheumatology, Hospital Universitario Príncipe de Asturias. Alcalá de Henares. Madrid. Spain, Alcalá de Henares, Madrid, Spain, ¹⁵Rheumatology, Hospital Moisès Broggi-Hospital General de L´Hospitalet. Consorci Sanitari Integral,, Barcelona, Spain, ¹⁶Rheumatology, Hospital de El Bierzo. León. Spain, León, Spain, ¹⁷Rheumatology, Hospital Universitario Doctor Peset. Valencia. Spain, Valencia, Spain, ¹⁸Rheumatology, Hospital Bellvitge. Barcelona. Spain, Barcelona, Spain, ¹⁹Rheumatology, Hospital Universitario de Salamanca. Spain, Salamanca, Spain, ²⁰Hospital de Pontevedra. Spain, Pontevedra, Spain, ²¹Rheumatology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ²²Rheumatology, Hospital Universitari Germans Trias i Pujol. Barcelona. Spain, Barcelona, Spain, ²³Rheumatology and Dermatology, Hospital Bellvitge. Barcelona. Spain, Barcelona, Spain, ²⁴Rheumatology, Hospital Clínico Universitario de Valencia. Spain, Valencia, Spain, ²⁵Pathology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ²⁶Rheumatology, Rheumatology. Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Behcet's syndrome, treatment and ulcers

Session Information

Date: Monday, October 22, 2018

Title: Vasculitis Poster II: Behҫet’s Disease and IgG4-Related Disease

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Behçet´s disease (BD) is characterized by recurrent oral and/or genital ulcers accompanied by ocular, cutaneous, articular, gastrointestinal, and/or neurologic manifestations. Oral and/or genital aphthous ulcers are often refractory to conventional treatment. Apremilast is an orally-active small molecule which inhibits phosphodiesterase-4 (PDE-4) that modulates some inflammatory pathways. Our aim was to assess the efficacy and safety of apremilast in BD patients with oral and/or genital ulcers refractory to conventional treatment.

Methods: National multicenter open-label study on 37 BD patients treated with apremilast at maintained standard dose of 30 mg twice daily, with the initial 5-day titration schedule in 31 cases. The main outcome was achievement of oral and/or genital ulcers remission. The diagnosis of BD was performed according to the proposed International Criteria for BD (1990) in 30 patients and according to the recently proposed criteria (2014) for BD in the rest of cases.

Results: We included 37 patients (26 women/11 men), mean age of 43.4±12.9 years. Before apremilast, all patients had received several systemic conventional drugs: oral corticosteroids (34), colchicine (36), methotrexate (21), azathioprine (20), mycophenolate mofetil (1), cyclosporine (7), dapsone (5), adalimumab (10), infliximab (5), tocilizumab (3), etanercept (1), and/or golimumab (1). The main clinical symptoms for starting apremilast were oral aphthous ulcers (36) and genital ulcers (22). Other manifestations present at apremilast onset were folliculitis/pseudofolliculitis (9), arthralgia/arthritis (8), asthenia (7), furunculosis (2), paradoxical psoriasis by TNFi (2), deep venous thrombosis (2), erythema nodosum (1), erythematosus and scaly skin lesions (1), ileitis (1) and fever (1). None of the patients presented visual manifestations at apremilast onset. TABLE shows the evolution of the patients. After a median follow-up of 6 [interquartile range, 4.5-11.5] months, most of the patients experienced clinical improvement. In this period of time, 26 patients developed any side-effect, most of them mild and during the first 3 months of treatment: nausea (10), diarrhea (10), dyspepsia (5), abdominal pain (5), headache (5), loss of appetite (4), weight loss (1), halitosis (1) and dry mouth (1). Four patients had to reduce the dose to 30 mg/day. Apremilast was discontinued in 10 patients due to: not obtaining the expected improvement (5), intense gastrointestinal adverse effects (3), desire of pregnancy (1) and development of neurological involvement (1).

Conclusion: Apremilast leads to a rapid and maintained improvement in many patients with refractory mucocutaneous ulcers of BD. Even in patients refractory to several systemic drugs including biologic therapy.

TABLE. Evolution of symptons and reduction of prednisone dose with apremilast therapy. Data are expressed as mean±SD or median[IQR].

	Basal n= 37	Week 1-2 n= 37	Week 4 n= 35	Month 3 n= 31	Month 6 n= 22	Month 12 n= 7
Resolution of main symptom, oral and/or genital ulcers n, (%)
Complete		17/37 (45.9)	19/35 (54.2)	20/31 (64.5)	13/22 (59.1)	4/7 (57.1)
Partial		14/37 (37.8)	6/35 (17.1)	1/31 (3.1)	2/22 (9.1)	2/7 (28.6)
Resolution of other symptoms n, (%)
Complete		10/23 (43.5)	8/21 (38.1)	11/17 (64.7)	4/8 (50.0)	4/6 (66.7)
Partial		3/23 (13.1)	3/21 (14.3)	4/17 (23.5)	3/8 (37.5)	2/6 (33.4)
Dose of prednisone (mg/day), median [IQR]	2.5 [0-10]	2.5 [0-10]	0 [0-8.1]*	0 [0-5]*	0 [0-3.7]*	0 [0-3.7]*

*p<0.05

Disclosure: B. Atienza-Mateo, None; J. L. Martín-Varillas, None; J. Loricera, None; G. Graña Gil, None; G. Espinosa, None; C. Moriano Morales, None; T. Pérez-Sandoval, None; M. Martín-Martínez, None; E. Díez, None; M. D. Garcia Armario, None; I. Castellví, None; F. Sivera, None; J. Calvo-Alén, None; I. de la Morena, None; F. Ortiz-Sanjuán, None; J. A. Román-Ivorra, None; A. Pérez Gómez, None; S. Heredia, None; C. Díez, None; J. Alegre, None; A. Ybáñez, None; J. Narváez, None; A. Turrión Nieves, None; S. Romero-Yuste, None; A. Olivé-Marqués, None; Á. Prior, None; E. Martínez, None; I. Figueras, None; P. Trénor, None; C. Gonzalez Vela, None; D. Prieto Peña, None; M. Calderón Goercke, None; J. L. Hernández, None; M. A. González-Gay, None; R. Blanco, None.

To cite this abstract in AMA style:

Atienza-Mateo B, Martín-Varillas JL, Loricera J, Graña Gil G, Espinosa G, Moriano Morales C, Pérez-Sandoval T, Martín-Martínez M, Díez E, Garcia Armario MD, Castellví I, Sivera F, Calvo-Alén J, de la Morena I, Ortiz-Sanjuán F, Román-Ivorra JA, Pérez Gómez A, Heredia S, Díez C, Alegre J, Ybáñez A, Narváez J, Turrión Nieves A, Romero-Yuste S, Olivé-Marqués A, Prior Á, Martínez E, Figueras I, Trénor P, Gonzalez Vela C, Prieto Peña D, Calderón Goercke M, Hernández JL, González-Gay MA, Blanco R. Apremilast in Refractory Oral and/or Genital Ulcers in Behçet’s Disease. Multicenter Study of 37 Cases [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/apremilast-in-refractory-oral-and-or-genital-ulcers-in-behcets-disease-multicenter-study-of-37-cases/. Accessed .

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