Long-term treatment with apremilast in hidradenitis suppurativa: A 2-year follow-up of initial responders

Abstract

To the Editor: In a previously published randomized controlled trial (RCT) among hidradenitis suppurativa (HS) patients with Hurley stage 1 and 2, we showed that the Hidradenitis Suppurativa Clinical Response (HiSCR) was met in 53.3% (8/15) of patients receiving apremilast 30 mg twice daily for 16 weeks compared with 0% (0/5) in the control group.1Vossen A.R.J.V. van Doorn M.B.A. van der Zee H.H. Prens E.P. Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial.J Am Acad Dermatol. 2019; 80: 80-88Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Responders continued treatment through a compassionate use program, and after 2 years of follow-up, we aimed to assess the longer-term clinical efficacy of apremilast in HiSCR responders from the initial RCT.After study completion, 100% (8/8) of the responders, all female, chose to continue treatment. Apremilast became available through a compassionate use program 3 to 4 months after the end of the RCT, and patients were assessed approximately every 3 months during routine clinical visits. Three patients reported an increase in symptoms while waiting for the compassionate use program.The 2-year follow-up data were available for 50% (4/8) of initial responders, with the other 4 discontinuing treatment within the first year. All patients (4/4) who continued treatment achieved HiSCR at both the 1-year and the 2-year follow-up visits compared with baseline (Table I). Two patients discontinued apremilast due to an active pregnancy wish at 3 and 6 months after reinitiating treatment. One patient reported intolerable nausea and discontinued after 6 months; another patient stopped treatment on her own after 6 months because she had no more HS symptoms. Manageable gastrointestinal adverse effects were reported by 2 out of 4 patients who continued treatment, 1 patient reported headaches, and 1 obese patient described weight loss of 11 kg. Overall, 75% (6/8) of the participants stated they would recommend apremilast to other patients, including the 2 participants who discontinued treatment because of an active pregnancy wish. One patient did not recommend treatment, and for 1 patient no answer was noted.Table IOverview of patients with moderate HS receiving apremilast in the 2-year follow-upPatient numberCharacteristicsAdverse effectsHiSCR during follow-upReason for discontinuationAge,∗Age at initial start of apremilast treatment. ySex, F/MSmokerBMI, kg/m2Hurley stage (1-3)HS-PGA (1-5)ComorbiditiesPrevious medical therapy†Dosage and duration of previous medical therapy was in accordance with current guidelines.ConcomitantHS therapy‡Concomitant therapy was used on an as-needed basis by patients with clindamycin 1% lotion recommended up to twice daily on already active lesions, and resorcinol 15% cream recommended once daily and up to 3 times a day on already active lesions.6 months12 months18 months24 months125FYes36.313AVSD, ADOral clindamycin + rifampicin, adalimumab, infliximab—NauseaDiarrhea————Pregnancy wish230FQuit24.713Hypercholesterolemia—Clindamycin 1% lotionResorcinol 15% creamDiarrheaUNKYesYesYes327FQuit31.113—Alitretinoin, oral minocycline, oral clindamycin—NauseaHeadache————Pregnancy wish448FYes35.323DM type 2, hypercholesterolemiaClindamycin 1% lotion, resorcinol 15% cream, oral clindamycin + rifampicin—NoYesYesYes527FNo35.013—Clindamycin 1% lotion, resorcinol 15% cream, oral doxycycline, alitretinoin, isotretinoin, oral clindamycin + rifampicinClindamycin 1% lotionHeadacheYesYesNoYes651FYes30.313MigraineResorcinol 15% cream, isotretinoin, oral doxycycline, oral clindamycin + rifampicinClindamycin 1% lotionResorcinol 15% creamNauseaWeight lossYesYesYesYes724FYes47.023Resorcinol 15% cream, oral clindamycin + rifampicin—NauseaDiarrhea————Nausea847FYes37.313ADD, PTSDClindamycin 1% lotion, resorcinol 15% cream, oral minocyclineClindamycin 1% lotionResorcinol 15% creamDiarrhea————Remission of diseaseAD, Atopic dermatitis; ADD, attention deficit disorder; AVSD, atrium-ventricular septum defect; BMI, body mass index; DM, diabetes mellitus; F, female; HiSCR, Hidradenitis Suppurativa Clinical Response; HS, hidradenitis suppurativa; HS-PGA, Hidradenitis Suppurativa Physician Global Assessment; M, male; PTSD, posttraumatic stress disorder; UNK, unknown.∗ Age at initial start of apremilast treatment.† Dosage and duration of previous medical therapy was in accordance with current guidelines.‡ Concomitant therapy was used on an as-needed basis by patients with clindamycin 1% lotion recommended up to twice daily on already active lesions, and resorcinol 15% cream recommended once daily and up to 3 times a day on already active lesions. Open table in a new tab Apremilast is a potential long-term treatment option in patients with HS, and this study shows prolonged clinical efficacy in initial responders after 1 and 2 years of treatment. Similar results were seen in a previously published case report describing stable disease course during 72 weeks of treatment.2Garcovich S. Giovanardi G. Malvaso D. De Simone C. Peris K. Apremilast for the treatment of hidradenitis suppurativa associated with psoriatic arthritis in multimorbid patients: case report and review of literature.Medicine (Baltimore). 2020; 99: e18991Crossref PubMed Scopus (4) Google Scholar In addition, a case series showed that 6 out of 9 patients continued treatment for a duration of 5 to 9 months.3Weber P. Seyed Jafari S.M. Yawalkar N. Hunger R.E. Apremilast in the treatment of moderate to severe hidradenitis suppurativa: a case series of 9 patients.J Am Acad Dermatol. 2017; 76: 1189-1191Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar However, clinical efficacy was assessed only 2 to 3 months after the start of treatment, and the reason for treatment discontinuation was not described. In our study, 2 patients with HS stopped treatment because of an active pregnancy wish. Apremilast is currently contraindicated in pregnancy based on a dose-related risk of abortion and fetal death found in animal studies.4Product Information. Otezla (apremilast) [package insert].https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205437s006lbl.pdfDate accessed: June 12, 2020Google Scholar This potentially influences the long-term use of apremilast in this female-biased disease, which presents itself in women's early reproductive years. A registry (NCT02775500) assessing the outcomes of pregnancies exposed to apremilast is currently underway.5Apremilast Pregnancy Exposure RegistryUS National Library of Medicine.https://clinicaltrials.gov/ct2/show/NCT02775500Date accessed: June 12, 2020Google ScholarIn conclusion, treatment with apremilast 30 mg twice daily shows prolonged efficacy after 1 and 2 years in patients who were able to continue treatment after initially achieving HiSCR at week 16. Although our small study shows promise for apremilast in the long-term treatment of HS, its long-term efficacy will need to be verified in a larger cohort. To the Editor: In a previously published randomized controlled trial (RCT) among hidradenitis suppurativa (HS) patients with Hurley stage 1 and 2, we showed that the Hidradenitis Suppurativa Clinical Response (HiSCR) was met in 53.3% (8/15) of patients receiving apremilast 30 mg twice daily for 16 weeks compared with 0% (0/5) in the control group.1Vossen A.R.J.V. van Doorn M.B.A. van der Zee H.H. Prens E.P. Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial.J Am Acad Dermatol. 2019; 80: 80-88Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Responders continued treatment through a compassionate use program, and after 2 years of follow-up, we aimed to assess the longer-term clinical efficacy of apremilast in HiSCR responders from the initial RCT. After study completion, 100% (8/8) of the responders, all female, chose to continue treatment. Apremilast became available through a compassionate use program 3 to 4 months after the end of the RCT, and patients were assessed approximately every 3 months during routine clinical visits. Three patients reported an increase in symptoms while waiting for the compassionate use program. The 2-year follow-up data were available for 50% (4/8) of initial responders, with the other 4 discontinuing treatment within the first year. All patients (4/4) who continued treatment achieved HiSCR at both the 1-year and the 2-year follow-up visits compared with baseline (Table I). Two patients discontinued apremilast due to an active pregnancy wish at 3 and 6 months after reinitiating treatment. One patient reported intolerable nausea and discontinued after 6 months; another patient stopped treatment on her own after 6 months because she had no more HS symptoms. Manageable gastrointestinal adverse effects were reported by 2 out of 4 patients who continued treatment, 1 patient reported headaches, and 1 obese patient described weight loss of 11 kg. Overall, 75% (6/8) of the participants stated they would recommend apremilast to other patients, including the 2 participants who discontinued treatment because of an active pregnancy wish. One patient did not recommend treatment, and for 1 patient no answer was noted. AD, Atopic dermatitis; ADD, attention deficit disorder; AVSD, atrium-ventricular septum defect; BMI, body mass index; DM, diabetes mellitus; F, female; HiSCR, Hidradenitis Suppurativa Clinical Response; HS, hidradenitis suppurativa; HS-PGA, Hidradenitis Suppurativa Physician Global Assessment; M, male; PTSD, posttraumatic stress disorder; UNK, unknown. Apremilast is a potential long-term treatment option in patients with HS, and this study shows prolonged clinical efficacy in initial responders after 1 and 2 years of treatment. Similar results were seen in a previously published case report describing stable disease course during 72 weeks of treatment.2Garcovich S. Giovanardi G. Malvaso D. De Simone C. Peris K. Apremilast for the treatment of hidradenitis suppurativa associated with psoriatic arthritis in multimorbid patients: case report and review of literature.Medicine (Baltimore). 2020; 99: e18991Crossref PubMed Scopus (4) Google Scholar In addition, a case series showed that 6 out of 9 patients continued treatment for a duration of 5 to 9 months.3Weber P. Seyed Jafari S.M. Yawalkar N. Hunger R.E. Apremilast in the treatment of moderate to severe hidradenitis suppurativa: a case series of 9 patients.J Am Acad Dermatol. 2017; 76: 1189-1191Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar However, clinical efficacy was assessed only 2 to 3 months after the start of treatment, and the reason for treatment discontinuation was not described. In our study, 2 patients with HS stopped treatment because of an active pregnancy wish. Apremilast is currently contraindicated in pregnancy based on a dose-related risk of abortion and fetal death found in animal studies.4Product Information. Otezla (apremilast) [package insert].https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205437s006lbl.pdfDate accessed: June 12, 2020Google Scholar This potentially influences the long-term use of apremilast in this female-biased disease, which presents itself in women's early reproductive years. A registry (NCT02775500) assessing the outcomes of pregnancies exposed to apremilast is currently underway.5Apremilast Pregnancy Exposure RegistryUS National Library of Medicine.https://clinicaltrials.gov/ct2/show/NCT02775500Date accessed: June 12, 2020Google Scholar In conclusion, treatment with apremilast 30 mg twice daily shows prolonged efficacy after 1 and 2 years in patients who were able to continue treatment after initially achieving HiSCR at week 16. Although our small study shows promise for apremilast in the long-term treatment of HS, its long-term efficacy will need to be verified in a larger cohort. We thank Celgene, now Amgen, for providing our patients with HS with apremilast through a compassionate use program.