Efficacy and Safety of Ustekinumab in Behçet's Disease

Journal Scan / Research · December 29, 2021

Journal of the American Academy of Dermatology

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• In this prospective, open-label, phase II study, 15 patients with Behçet's disease and ≥2 episodes of oral or genital ulcers within the last 3 months resistant to colchicine were treated with subcutaneous ustekinumab 90 mg at 0, 4, and 16 weeks. At week 24, 9 of 15 patients had a complete response and 2 of 15 patients had a partial response. The number of oral ulcers decreased from 2.1±1.3 to 0.3±0.5. Disease activity and quality of life scores improved.

• Ustekinumab is a promising treatment option for patients with Behçet's disease refractory to colchicine.

–  Katherine M. Stiff, MD

Written by

 

 

David Fivenson MD, FAAD

Behcet's disease (BD) is a rare condition (overall prevalence of 1 to 2 per million) characterized by relapsing oral and genital aphthous-type ulcers, ocular inflammation, arthritis, pustular skin eruptions, and pyoderma gangrenosum as well as neurologic, pulmonary, and renal disease. It is more common in the so-called Silk Road descendants, with a prevalence of 2  per 10,000 in the Mediterranean countries and 4 per 1000 in China. It is a clinical diagnosis with major and minor diagnostic criteria, but aphthous ulcers are almost universally seen in BD patients. Treatments for BD run the gamut of tools from our autoimmune disease toolbox and beyond. Oral and genital ulcers are treated with topical steroids, topical tacrolimus, topical pimecrolimus, colchicine, pentoxifylline, and dapsone, and apremilast has been recently approved by the FDA as the first medication with a BD indication. Other agents that have had case series or clinical trials published include azathioprine, methotrexate, chlorambucil, mycophenolate mofetil, leflunomide, cyclophosphamide, cyclosporin, tacrolimus, interferon alpha, thalidomide, zinc sulfate, and levamisole, along with numerous biologic agents, including inhibitors of CD20, TNF alpha, TNF alpha receptor, IL-1α, IL-1β, IL-1R, IL-2R, IL-6R, and IL-17.1

In the article by London et al, the authors present results of a phase II trial of ustekinumab (inhibitor of IL-12/IL-23) for oral ulcers that have not responded to colchicine in BD patients. They report results from 15 participants in this open-label trial of 90 mg ustekinumab at standard dosing schedule as used in psoriasis of weeks 0 and 4 and then every 12 weeks. At the primary endpoint of week 24, they found 9 complete responders, 2 partial responders and 3 non-responders; 1 patient was lost to follow-up. However, the graphic representations of results show rapid improvement in these ulcers by week 4 (ie, after one dose of ustekinumab). This is very encouraging, as we would hope that inhibition of the TH17 pathway would impact this painful condition much as it is showing promise in other autoimmune and auto-inflammatory conditions like psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and inflammatory bowel diseases. Larger studies are needed, and placebo controls or standard-of-care populations are needed to better clarify these preliminary findings. It remains to be shown but is expected that other biologic therapies targeting IL-23 will have similar efficacy. 

Treatment of BD can be as challenging as it is sometimes to diagnose. Targeted immune modulation through anti-cytokine therapies is proving to be a safer, more effective approach in many autoimmune/auto-inflammatory disease.

Reference

1.  McNally TW, Damato EM, Murray PI, et al. An update on the use of biologic therapies in the management of uveitis in Behçet's disease: a comprehensive review. Orphanet J Rare Dis. 2017;12(1):130. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513401/pdf/13023_2017_Article_681.pdf

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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