Treatment of mucocutaneous manifestations in Behçet's disease with anakinra: A pilot open-label study

Peter C. Grayson, Yusuf Yazici, Melissa Merideth, H. Nida Sen, Michael Davis, Elaine Novakovich, Elizabeth Joyal, Raphaela Goldbach-Mansky, Cailin Sibley

Research output: Contribution to journalArticle

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Abstract

Background: The effect of IL-1 blocking therapy on mucocutaneous manifestations of Behçet's disease is incompletely understood. Methods: Six patients with Behçet's disease and ongoing oral/genital ulcers for ≥1 month were enrolled into an adaptive, two-phase clinical trial and included in the analysis. Study duration was 6 months with extension up to 16 months. All were treated non-blinded with anakinra 100 mg subcutaneous daily with the option to escalate the dose to 200 mg in partial responders after 1 month and 300 mg after 6 months. Patients recorded the number and severity of ulcers in daily diaries. The primary outcome was remission defined as no ulcers on physical exam for two consecutive monthly visits between months 3 and 6. Secondary outcomes included the number and severity of patient-reported ulcers, patient/physician global scores, and standardized disease activity scores. Results: Two of six patients achieved the primary outcome. Five of six patients had improvement in the number and severity of ulcers. Non-statistically significant improvements were seen in secondary outcomes. Over the entire study, patients reported ≥1 oral and ≥1 genital ulcer on 665 (66%) and 139 (14%) days, respectively. On anakinra 200 mg vs 100 mg, patients reported fewer days with oral ulcers (65% vs 74% of days, p = 0.01) and genital ulcers (10% vs 22% of days, p < 0.001) and milder oral ulcer severity (p < 0.001). Increase of anakinra to 300 mg did not result in further improvements. Adverse events were notable for mild infections. Conclusion: Anakinra at an optimal dose of 200 mg daily had an acceptable safety profile and was partially effective in the treatment of resistant oral and genital ulcers in Behçet's disease. Trial registration: Clinicaltrials.gov. NCT01441076. Registered on 24 September 2011.

Original languageEnglish (US)
Article number69
JournalArthritis Research and Therapy
Volume19
Issue number1
DOIs
StatePublished - Mar 24 2017

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Interleukin 1 Receptor Antagonist Protein
Oral Ulcer
Ulcer
Therapeutics
Interleukin-1
Clinical Trials
Physicians
Safety

Keywords

  • Anakinra
  • Autoinflammatory disease
  • Behçet's disease
  • Clinical trial
  • Vasculitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Grayson, P. C., Yazici, Y., Merideth, M., Sen, H. N., Davis, M., Novakovich, E., ... Sibley, C. (2017). Treatment of mucocutaneous manifestations in Behçet's disease with anakinra: A pilot open-label study. Arthritis Research and Therapy, 19(1), [69]. https://doi.org/10.1186/s13075-017-1222-3

Treatment of mucocutaneous manifestations in Behçet's disease with anakinra : A pilot open-label study. / Grayson, Peter C.; Yazici, Yusuf; Merideth, Melissa; Sen, H. Nida; Davis, Michael; Novakovich, Elaine; Joyal, Elizabeth; Goldbach-Mansky, Raphaela; Sibley, Cailin.

In: Arthritis Research and Therapy, Vol. 19, No. 1, 69, 24.03.2017.

Research output: Contribution to journalArticle

Grayson, PC, Yazici, Y, Merideth, M, Sen, HN, Davis, M, Novakovich, E, Joyal, E, Goldbach-Mansky, R & Sibley, C 2017, 'Treatment of mucocutaneous manifestations in Behçet's disease with anakinra: A pilot open-label study', Arthritis Research and Therapy, vol. 19, no. 1, 69. https://doi.org/10.1186/s13075-017-1222-3
Grayson, Peter C. ; Yazici, Yusuf ; Merideth, Melissa ; Sen, H. Nida ; Davis, Michael ; Novakovich, Elaine ; Joyal, Elizabeth ; Goldbach-Mansky, Raphaela ; Sibley, Cailin. / Treatment of mucocutaneous manifestations in Behçet's disease with anakinra : A pilot open-label study. In: Arthritis Research and Therapy. 2017 ; Vol. 19, No. 1.
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abstract = "Background: The effect of IL-1 blocking therapy on mucocutaneous manifestations of Beh{\cc}et's disease is incompletely understood. Methods: Six patients with Beh{\cc}et's disease and ongoing oral/genital ulcers for ≥1 month were enrolled into an adaptive, two-phase clinical trial and included in the analysis. Study duration was 6 months with extension up to 16 months. All were treated non-blinded with anakinra 100 mg subcutaneous daily with the option to escalate the dose to 200 mg in partial responders after 1 month and 300 mg after 6 months. Patients recorded the number and severity of ulcers in daily diaries. The primary outcome was remission defined as no ulcers on physical exam for two consecutive monthly visits between months 3 and 6. Secondary outcomes included the number and severity of patient-reported ulcers, patient/physician global scores, and standardized disease activity scores. Results: Two of six patients achieved the primary outcome. Five of six patients had improvement in the number and severity of ulcers. Non-statistically significant improvements were seen in secondary outcomes. Over the entire study, patients reported ≥1 oral and ≥1 genital ulcer on 665 (66{\%}) and 139 (14{\%}) days, respectively. On anakinra 200 mg vs 100 mg, patients reported fewer days with oral ulcers (65{\%} vs 74{\%} of days, p = 0.01) and genital ulcers (10{\%} vs 22{\%} of days, p < 0.001) and milder oral ulcer severity (p < 0.001). Increase of anakinra to 300 mg did not result in further improvements. Adverse events were notable for mild infections. Conclusion: Anakinra at an optimal dose of 200 mg daily had an acceptable safety profile and was partially effective in the treatment of resistant oral and genital ulcers in Beh{\cc}et's disease. Trial registration: Clinicaltrials.gov. NCT01441076. Registered on 24 September 2011.",
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