Tofacitinib Evaluated as Possible Treatment for Cutaneous Sarcoidosis

William Damsky, MD, PhD, assistant professor of dermatology and pathology at Yale School of Medicine, New Haven, Connecticut, spoke on a recent trial (NCT03910543) which evaluates tofacitinib as a treatment for sarcoidosis at the American Academy of Dermatology Virtual Experience 2021 (AAD VMX 2021).¹

Cutaneous sarcoidosis is an idiopathic inflammatory disorder that is most common among Black women. About 1 in 25 Black women will develop this disorder during their lifetimes. As many as 4,000 deaths per year are either directly or indirectly attributed to sarcoidosis. It affects almost every organ, including the lungs and lymph nodes, which are most common, but also heart, eyes, and other areas of the body. Approximately one-third of patients experience skin-related symptoms.

In a preclinical trial, a patient tested was a 48-year-old female with 8 years of both pulmonary and cutaneous sarcoidosis. About 15% of her body surface area (BSA) was involved and multiple treatments were tested. The patient was then switched to tofacitinib 5 mg (Xeljanz, Pfizer). Tofacitinib is an oral Janus kinase (JAK) 1 inhibitor.

“She had a really remarkable response to therapy,” explained Damsky. “Such that her active sarcoid plaques turned into just post-inflammatory hyper-pigmentation over the period of 9 months.”

Biopsies were done on the patient’s skin before and after treatment. The patient exhibited improvement from baseline and a negative p-STAT immunohistochemistry (IHC).

Currently, there is only1 FDA-approved treatment, prednisone (Deltasone, Geneyork Pharmaceutical), but it is only intended for pulmonary sarcoidosis. Patients may also be transitioned to methotrexate or tumor necrosis factor (TNF) α blockers. 

There are many approaches for treatment of cutaneous sarcoidosis such as:

• Topicals 
• Intralesional 
• Antimalarials
• Minocycline 
• Methotrexate 
• Thalidomide 
• Adalimumab (Humira, AbbVie)
• Infliximab (Avsola, Janssen Biotech)

The trial was an open label study that included 10 sarcoidosis patients with cutaneous involvement, 9 of which also had active internal organ disease. Tofacitinib was administered at 5 mg twice daily for 6 months. 

Patients enrolled had to meet the following criteria: 18 years or older, be diagnosed of cutaneous sarcoidosis with supportive biopsy, Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score of 10 or greater, and if any other systemic therapies for treatment of sarcoidosis, needed to be on a stable regimen for at least 3 months. 

Primary outcomes were CSAMI change after 6 months of treatment. Patients were allowed to continue, lessen, or discontinue concomitant immunosuppressive agents while participating in the trial. Secondary outcomes included changes in internal organ sarcoidosis, quality of life metric (Skindex-16), histologic and molecular finding in skin, and molecular findings in plasma.

Baseline characteristic for those enrolled were patients in their 50s to early 60s, 6 were male and 4 were female, most had long standing disease, had failed a number of previous therapies, and had numerous different skin types.

Additional results of the study show an average reduction in CSAMI score of 82.7%. All patients saw improvement at Day 180 and 6 patients achieved a CSAMI score of 0. Most patients were able to significantly taper or discontinue their baseline immunosuppressive regimen, including prednisone. All patients completed the study, with tofacitinib being well-tolerated and no serious adverse events (SAE)s were noted, according to Dumsky.

Systemic response data and mechanistic data will be presented at a future date.

References:

1. Damsky, W. Treatment of Sarcoidosis with Cutaneous Involvement with Tofacitinib: Results of an Open-Label Clinical Trial. Presented at the: American Academy of Dermatology Virtual Meeting Experience 2021 (AAD VMX); Virtual.