Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial

doi:10.1016/j.jaad.2018.06.046

Journal of the American Academy of Dermatology

Volume 80, Issue 1, January 2019, Pages 80-88

https://doi.org/10.1016/j.jaad.2018.06.046 Get rights and content

Background

Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited.

Objective

To evaluate the efficacy and short-term safety of apremilast in patients with moderate HS.

Methods

A total of 20 patients with moderate HS were randomized in a 3:1 ratio to receive blinded treatment with apremilast, 30 mg twice daily, or placebo for 16 weeks. The primary outcome was the Hidradenitis Suppurativa Clinical Response at week 16. Linear mixed effects modeling (analysis of covariance) was used to assess secondary clinical outcomes between treatment groups.

Results

The HS clinical response was met in 8 of 15 patients in the apremilast group (53.3%) and none of 5 patients in the placebo group (0%) (P = .055) at week 16. Moreover, the apremilast-treated patients showed a significantly lower abscess and nodule count (mean difference, –2.6; 95% confidence interval, –6.0 to –0.9; P = .011), NRS for pain (mean difference, –2.7; 95% –4.5 to –0.9; P = .009), and itch (mean difference, –2.8; 95% confidence interval, –5.0 to –0.6; P = .015) over 16 weeks compared with the placebo-treated patients. There was no significant difference in the Dermatology Life Quality Index over time between the 2 treatment groups (mean difference, –3.4; 95% confidence interval, –9.0 to 2.3; P = .230). The most frequently reported adverse events in the apremilast-treated patients were mild-to-moderate headache and gastrointestinal symptoms, which did not result in dropouts.

Limitations

Small number of patients, relatively short study duration.

Conclusion

Apremilast, at a dose of 30 mg twice daily, demonstrated clinically meaningful efficacy and was generally well tolerated in patients with moderate HS.

Section snippets

Patients

Patients who were at least 18 years of age with moderate HS, defined as a HS-PGA score of 3, were enrolled. Additionally, patients were required to have at least 4 inflammatory lesions (ie, abscesses, draining sinuses/tunnels, or inflammatory nodules in at least 2 anatomic locations). Patients receiving systemic antibiotics or immunosuppressive/immunomodulating therapy were required to stop treatment at least 28 days before baseline and until the end of study. Patients were excluded if they had

Patients

Enrollment occurred between February and August 2017, and a 16-week follow-up was completed in December 2017. In total, 21 patients were randomized, of whom 20 received at least 1 dose of study medication and were included in the intention-to-treat population. Of these, 18 (90%) completed the week 16 follow-up visit (Fig 1). Of the 15 patients receiving apremilast, 2 (13%) discontinued the study: 1 patient discontinued between week 4 and week 8 because of personal circumstances (travel distance

Discussion

The main finding from this study was a clinically meaningful improvement of moderate HS after treatment with apremilast at a dose of 30 mg twice per day for 16 weeks. Apremilast significantly decreased disease activity as measured by the AN count, and 53.3% of patients receiving apremilast achieved the HiSCR in comparison with none of the patients receiving placebo. In addition, apremilast for 16 weeks was well tolerated by patients with moderate HS. According to the study protocol, the

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Cited by (84)

Topical and Intralesional Therapies for Hidradenitis Suppurativa: A Systematic Literature Review
2024, Actas Dermo-Sifiliograficas
Topical and intralesional (IL) treatments may be considered the first-line therapy in patients with hidradenitis suppurativa (HS); however, the evidence supporting their use is limited. The aim of our review is to evaluate the efficacy and safety profile of topical and IL treatments in patients with HS.
We designed a systematic review of the current medical literature available following the PICO(T) method. And including all types of studies (Study type [T]) of individuals with HS of any sex, age, and ethnicity (Population [P]) who received any topical or IL treatment for HS (Intervention [I]) compared to placebo, other treatments, or no treatment at all (Comparator [C]), and reported efficacy and/or safety outcomes (Outcomes [O]). Two outcomes were defined: quality of life and the no. of patients with, at least, one adverse event. The search was conducted in the Cochrane Library, MEDLINE, and EMBASE databases; study selection was performed based on pre-defined criteria. The risk of bias was determined in each study.
We obtained a total of 11,363 references, 31 of which met the inclusion criteria. These studies included 1143 patients with HS, 62% of whom were women. A total of 10, 8, 6, 2, and 5 studies, respectively, evaluated the use of photodynamic therapy (PDT), glucocorticoids, resorcinol, topical antibiotics, and other interventions. Most articles were case series (n = 25), with only five randomized clinical trials (RCTs) and one cohort study. RCTs showed improvement in disease activity with topical clindamycin and botulinum toxin (BTX) vs placebo, and PDT with methylene blue (MB) niosomal vs free MB; however, intralesional triamcinolone acetonide was not superior to placebo. The risk of bias was low in three RCTs and high in two RCTs.
The quality of evidence supporting the use of topical, or IL treatments is low. However, it supports the use of topical clindamycin, PDT, and BTX. Well-designed RCTs with standardized outcomes and homogeneous populations of patients and lesions are needed to support decision-making in the routine clinical practice.
Los tratamientos tópicos e intralesionales (IL) pueden ser considerados como tratamientos de primera línea en pacientes con hidradenitis supurativa (HS), sin embargo, la evidencia apoyando su uso es limitada. El objetivo de nuestra revisión es evaluar la eficacia y la seguridad de los tratamientos tópicos e IL en pacientes con HS.
Diseñamos una revisión sistemática de la literatura siguiendo el método PICO(T). Incluimos todo tipo de estudios (tipo de estudio [T]) que incluyeran individuos con HS de cualquier sexo, edad, y etnicidad (Población [P]), que recibieran cualquier tratamiento tópico o IL para la HS (Intervención [I]) que compararan con placebo, otros tratamientos o no tratamiento (comparador [C]) y reportaran resultados de eficacia y/o seguridad (Outcomes [O]). Dos resultados fueron definidos: calidad de vida y número de pacientes con al menos un efecto adverso. La búsqueda se llevó a cabo en las bases de datos Cochrane Library, MEDLINE y EMBASE; la selección de estudios se realizó de acuerdo con los criterios predefinidos. El riesgo de sesgo se determinó en cada estudio.
Se obtuvieron 11.363 referencias de las cuales 31 cumplieron los criterios de inclusión. Estos estudios incluyeron 1.143 pacientes con HS, 62% fueron mujeres. 10 estudios evaluaron la terapia fotodinámica (TFD), ocho glucocorticoides, seis resorcinol, dos antibióticos tópicos y cinco otras intervenciones. La mayoría de los artículos fueron series de casos (n = 25), con solo cinco ensayos clínicos aleatorizados (ECA) y un estudio de cohortes. Los ECA demostraron mejoría de la actividad de la enfermedad con clindamicina tópica y con toxina botulínica (BTX) frente a placebo y TFD con azul de metileno (AM) niosomal frente a AM libre; sin embargo, el acetónido de triamcinolona IL no fue superior al placebo. El riesgo de sesgo fue bajo en tres y alto en dos ECA.
La calidad de la evidencia que apoya el uso de tratamientos tópicos o IL es baja, pero apoya el uso de clindamicina tópica, TFD y BTX. Se requieren ECA adecuadamente diseñados con resultados estandarizados y poblaciones homogéneas de pacientes y lesiones para apoyar la toma de decisiones en la práctica clínica.
Narrative Review and Update on Biologic and Small Molecule Drugs for Hidradenitis Suppurativa: An Entity With a Promising Future
2023, Actas Dermo-Sifiliograficas
Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine regions. In addition to its dermatological involvement, it is associated with multiple systemic comorbidities. Its treatment is combined: topical pharmacological, systemic pharmacological and surgical. Regarding biologic or small molecule drugs, currently only adalimumab is approved. A narrative review of the literature on biological or small molecule drugs used in the treatment of hidradenitis suppurativa is presented. The arsenal we found is large, with multiple targets: inhibitors of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, IL-23, IL-1, inhibitors of the janus kinase (JAK) pathway, and multiple other drugs in study. New prospective studies and comparative trials are needed to analyze the effectiveness and safety of these treatments, in an entity with a promising future.
La hidradenitis supurativa (HS) es una entidad inflamatoria crónica caracterizada por la aparición de múltiples nódulos, abscesos y fístulas, de predominio en regiones apocrinas. Además de su afectación dermatológica, se asocia a múltiples comorbilidades sistémicas. Su tratamiento es combinado: farmacológico tópico, farmacológico sistémico y quirúrgico. En cuanto a los medicamentos biológicos o de molécula pequeña, actualmente solo se encuentra aprobado adalimumab. En este artículo, se presenta una revisión narrativa de la literatura sobre fármacos biológicos o de molécula pequeña utilizados en el tratamiento de la hidradenitis supurativa. El arsenal que encontramos es numeroso, con múltiples dianas: inhibidores del factor de necrosis tumoral alfa (TNF-alfa), interleucina (IL)-17, IL-23, IL-1, inhibidores de la vía Janus kinasa (JAK) u otros múltiples fármacos en estudio. Son necesarios nuevos estudios prospectivos y ensayos comparativos que analicen la eficacia y seguridad de estos tratamientos, en una entidad con un futuro prometedor.
Assessment tools and phenotype classification for hidradenitis suppurativa
2023, Clinics in Dermatology
Hidradenitis suppurativa (HS) is a heterogeneous chronic relapsing skin disease. Several assessment tools are used to assess disease severity and to classify disease phenotype; however, no consensus exists. This review evaluates the various assessment tools and phenotypes, assessing their validity and reliability. Numerous assessment tools and phenotype classifications have been proposed for identifying various subtypes within the hidradenitis suppurativa disease spectrum. Each has a different purpose, such as use in daily practice or in clinical trial settings. Several assessment tools and phenotype classifications have been validated but not always with satisfactory results and often with studies showing divergent intra-rater reliability results. A consensus is needed for a validated, easy-to-use, and timesaving assessment tool for routine daily practice. For clinical trials, a validated and extensive assessment tool that also measures response to treatment is also needed.
The successful use of oral apremilast for a case of dissecting cellulitis
2023, JAAD Case Reports
Evaluating the Impact of Exclusion Criteria on the Generalizability of Hidradenitis Suppurativa Treatment Research
2023, JID Innovations
Exclusion criteria can limit the generalizability and translation of research findings into clinical practice. The objective of this study is to characterize the trends of exclusion criteria and explore the impact of exclusion criteria on participant diversity, length of enrollment, and the number of enrolled participants. A detailed search was performed using PubMed and clinicaltrials.gov. Nineteen published randomized controlled trials were included, where 2,664 patients were screened, and 2,234 patients (mean age: 37.6 years, 56.6% female) were enrolled from 25 countries. On average, there were 10.1 (standard deviation: 6.14, range: 3−25) exclusion criteria per randomized controlled trial. There was a weak to moderate positive correlation between the number of exclusion criteria and the proportion of enrolled participants (R = 0.49, P value = 0.040). However, no association was seen between the number of exclusion criteria, number of enrolled Black participants (R = 0.86, p value = 0.08), and enrollment length (R = 0.083, P value = 0.74). In addition, there was no discernable trend in the number of exclusion criteria over time (R = −0.18, P value = 0.48). Although the number of exclusion criteria appeared to impact the number of enrolled participants, the lack of skin of color representation in hidradenitis suppurativa randomized controlled trials does not appear to be influenced by the number of exclusion criteria.
New horizons in the medical treatment of hidradenitis suppurativa
2023, Piel

View all citing articles on Scopus

: Funding sources: Sponsored by Celgene.

: Disclosure: Dr van der Zee is an advisory board member for AbbVie, InflaRX, and Galderma. Dr Prens is a consultant, speaker, and/or principal investigator and/or has received grants from Abbvie, Amgen, Biogen, Celgene, Eli Lilly and Company, Janssen-Cilag, Novartis, Pfizer, and UCB. Dr van Doorn is a consultant, speaker, and/or principal investigator and/or has received grants from Abbvie, Celgene, Eli Lilly and Company, Janssen-Cilag, Novartis, Pfizer, Cutanea Life Sciences, and Idera Pharmaceuticals. Dr Vossen has no conflicts of interest to disclose.

: Reprints not available from the authors.

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Original articleApremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Patients

Patients

Discussion

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Invest Dermatol

Lancet

Clinical practice. Hidradenitis suppurativa

N Engl J Med

Assessing pruritus in hidradenitis suppurativa: a cross-sectional study

Am J Clin Dermatol

Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial

Ann Intern Med

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

J Eur Acad Dermatol Venereol

Two phase 3 trials of adalimumab for hidradenitis suppurativa

N Engl J Med

Investigational drugs in clinical trials for hidradenitis suppurativa

Expert Opin Investig Drugs

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)

Ann Rheum Dis

Original article
Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial