Apremilast in Combination vs Monotherapy for Refractory Oral And/or Genital Ulcers in Behçet’s Disease: National Multicenter Study of 51 Cases

Belén Atienza-Mateo¹, Mónica Calderón-Goercke ², DIANA PRIETO- PENA ³, Iñigo Gonzalez-Mazon ³, Lara Sanchez-Bilbao ¹, Jose Luis Martín-Varillas ¹, Javier Loricera ⁴, Vanesa Calvo Río ¹, Jenaro Graña ⁵, Gerard Espinosa ⁶, Clara Moriano ⁷, Trinidad Pérez-Sandoval ⁷, Manuel Martín-Martínez ⁷, Elvira Díez ⁷, María Dolores García-Armario ⁸, Esperanza Martínez ⁸, Ivan Castellvi ⁹, Patricia Moya Alvarado ¹⁰, Francisca Sivera ¹¹, Jaime Calvo-Alen ¹², Isabel de la Morena ¹³, Francisco Ortiz-Sanjuán ¹⁴, José Andrés Román-Ivorra ¹⁴, Ana Pérez-Gómez ¹⁵, Sergi Heredia ¹⁶, Alejandro Olivé-Marqués ¹⁶, Águeda Prior-Español ¹⁷, Carolina Díez ¹⁸, Juan José Alegre-Sancho ¹⁹, Amparo Ybáñez ¹⁹, Ángels Martínez-Ferrer ¹⁹, Javier Narváez ²⁰, Ignasi Figeras ²¹, Ana Turrión ²², Susana Romero-Yuste ²³, Pilar Trénor ²⁴, Soledad Ojeda ²⁵, Miguel Á. González-Gay ²⁶ and Ricardo Blanco ²⁶, ¹Rheumatology, Hospital Universitario Marques de Valdecilla, Santander, Spain, ²Hospital Marqués de Valdecilla, Santander, Cantabria, Spain, ³Rheumatology, Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Spain, ⁴Rheumatology Department. Hospital Marqués de Valdecilla, Santander, Cantabria, Spain, ⁵Centro Médico Quirón A Coruña, A Coruña, Galicia, Spain, ⁶Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Barcelona, Catalonia, Spain, ⁷Complejo Asistencial Universitario de León, León, Castilla y Leon, Spain, ⁸Hospital Lluís Alcanyís, Xàtiva, Comunidad Valenciana, Spain, ⁹Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, ¹⁰Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain, ¹¹Hospital General Universitario de Elda, Elda, Spain, ¹²Hospital Universitario Araba, Vitoria-Gasteiz, Spain, ¹³Hospital General Universitario de Valencia, Valencia, Comunidad Valenciana, Spain, ¹⁴Hospital Universitario y Politécnico La Fe, Valencia, Comunidad Valenciana, Spain, ¹⁵Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain, ¹⁶Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain, ¹⁷Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ¹⁸Hospital de El Bierzo, León, Castilla y Leon, Spain, ¹⁹Hospital Universitario Doctor Peset, Valencia, Comunidad Valenciana, Spain, ²⁰Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain, ²¹Hospital Bellvitge, Barcelona, Catalonia, Spain, ²²Hospital Clínico Universitario de Salamanca, Salamanca, Spain, ²³Complejo Hospitalario Universitario Pontevedra, Pontevedra, Galicia, Spain, ²⁴Hospital Clínico Universitario de Valencia, Valencia, Comunidad Valenciana, Spain, ²⁵Hospital Doctor Negrín, Las Palmas de Gran Canaria, Canarias, Spain, ²⁶Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Behcet's syndrome, ulcers and apremilast

Session Information

Date: Monday, November 11, 2019

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III: Behçet’s Disease & Other Vasculitides

Session Type: Poster Session (Monday)

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

Background/Purpose: Oral and/or genital aphthous ulcers are the most common symptoms of Behçet´s disease (BD), and are often refractory to conventional treatment. The inhibitor of phosphodiesterase-4 apremilast (APR) has demonstrated efficacy in the treatment of this manifestations. Our aim was to compare the efficacy and safety of APR in monotherapy or combined with disease-modifying anti-rheumatic drugs (DMARDs) in BD patients with oral and/or genital ulcers refractory to conventional treatment.

Methods: National multicenter open-label study on 51 BD patients treated with APR at maintained standard dose of 30 mg twice daily. The main outcome was achievement of oral and/or genital ulcers remission.

Results: We included 51 patients (35 women/16 men), mean age of 47.7±13.2 years. Before APR, all patients had received several systemic conventional drugs. The main clinical symptoms for starting APR were oral (n=19) and genital (n=2) aphthous ulcers or both (n=30). Other manifestations present at APR onset were: arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), asthenia (n=7), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis by TNFi (n=2), ileitis (n=2), deep venous thrombosis (n=2), erythematosus and scaly skin lesions (n=1), fever (n=1), eating disorder (n=1), fibromyalgia (n=1), unilateral anterior uveitis (n=1) and neurobehçet (n=1).

Excluding corticosteroids, colchicine or NSAIDs, APR was given in monotherapy in 31 cases or combined with conventional or biologic DMARDs in 20. There were not found statistically significant differences in baseline characteristics or sides effects, neither in previous treatment, except for tocilizumab that was more frequent in the combined group. The main demographic and clinical features are shown in TABLE 1.

After a mean follow-up of 8.45±6.9 months, most of the patients experienced clinical improvement in both groups, without statistically significant differences. TABLE shows the evolution of the mucocutaneus manifestations in each group, combined vs monotherapy. In this period of time, 33 patients developed any side-effect (TABLE 1), 11 (55%) patients in the combined group and 22 (70%) patients in the monotherapy group), most of them mild and during the first 3 months of treatment.

Apremilast was discontinued in 11 patients due to: not obtaining the expected improvement (5), intense gastrointestinal adverse effects (n=4), desire of pregnancy (n=1) and development of neurological involvement (n=1).

Conclusion: Apremilast leads to a rapid and maintained improvement in many patients with highly refractory mucocutaneous ulcers of BD. This therapy seems as effective and safe in monotherapy as in combination with DMARDs.

TABLE 1 APR

TABLE 1. Main baseline features and follow-up of a series of 31 patients with refractory oral and/or genital ulcers due to Behçet’s disease undergoing apremilast -APR- in combination or monotherapy.

TABLE 2 APR

TABLE 2. Evolution of main symptoms with apremilast in combination vs monotherapy.

Disclosure: B. Atienza-Mateo, None; M. Calderón-Goercke, None; D. PRIETO- PENA, None; I. Gonzalez-Mazon, None; L. Sanchez-Bilbao, None; J. Martín-Varillas, None; J. Loricera, None; V. Calvo Río, None; J. Graña, None; G. Espinosa, None; C. Moriano, None; T. Pérez-Sandoval, None; M. Martín-Martínez, None; E. Díez, None; M. García-Armario, None; E. Martínez, None; I. Castellvi, Actelion, 5, Boehringer -Ingelheim, 8, Gebro, 8, Kern, 5, Novartis, 8; P. Moya Alvarado, None; F. Sivera, None; J. Calvo-Alen, None; I. de la Morena, None; F. Ortiz-Sanjuán, None; J. Román-Ivorra, None; A. Pérez-Gómez, None; S. Heredia, None; A. Olivé-Marqués, None; �. Prior-Español, None; C. Díez, None; J. Alegre-Sancho, None; A. Ybáñez, None; �. Martínez-Ferrer, None; J. Narváez, None; I. Figeras, None; A. Turrión, None; S. Romero-Yuste, None; P. Trénor, None; S. Ojeda, None; M. González-Gay, None; R. Blanco, None.

To cite this abstract in AMA style:

Atienza-Mateo B, Calderón-Goercke M, PRIETO- PENA D, Gonzalez-Mazon I, Sanchez-Bilbao L, Martín-Varillas J, Loricera J, Calvo Río V, Graña J, Espinosa G, Moriano C, Pérez-Sandoval T, Martín-Martínez M, Díez E, García-Armario M, Martínez E, Castellvi I, Moya Alvarado P, Sivera F, Calvo-Alen J, de la Morena I, Ortiz-Sanjuán F, Román-Ivorra J, Pérez-Gómez A, Heredia S, Olivé-Marqués A, Prior-Español �, Díez C, Alegre-Sancho J, Ybáñez A, Martínez-Ferrer �, Narváez J, Figeras I, Turrión A, Romero-Yuste S, Trénor P, Ojeda S, González-Gay M, Blanco R. Apremilast in Combination vs Monotherapy for Refractory Oral And/or Genital Ulcers in Behçet’s Disease: National Multicenter Study of 51 Cases [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/apremilast-in-combination-vs-monotherapy-for-refractory-oral-and-or-genital-ulcers-in-behcets-disease-national-multicenter-study-of-51-cases/. Accessed .

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