Please login or create an account. If you do not have access to this content, you will be shown a 30 second preview and licensing options.
- Presentation
JAK Inhibitors and Granulomatous Diseases Update
Description
The discussion focused on the use of JAK inhibitors, particularly tofacitinib, in treating granulomatous diseases, specifically sarcoidosis and granuloma annulare. The speaker shared their initial experiences treating a patient with recalcitrant cutaneous sarcoidosis that had previously failed various therapies. Remarkably, this patient responded well to tofacitinib, prompting further studies. In a small clinical trial involving 10 patients with cutaneous sarcoidosis, results showed six complete responders and significant improvements in skin and internal organ involvement. The JAK-STAT pathway's activation, especially with interferon gamma, was highlighted as a potential key mechanism in sarcoidosis treatment. Similar observations were made in granuloma annulare, where a small open-label study indicated also promising outcomes, although not all patients may be suitable candidates for JAK inhibitors due to possible side effects. The speaker noted the need for controlled studies and further pharmaceutical interest to substantiate their findings. They concluded by emphasizing the necessity of advanced clinical trials for both conditions to better evaluate the effectiveness and safety of JAK inhibitors.
View moreConclusions
- Tofacitinib treatment leads to significant improvement in patients with recalcitrant cutaneous sarcoidosis and granulomatous diseases.
- In an open-label trial, 6 out of 10 patients with longstanding sarcoidosis achieved complete response with tofacitinib.
- Most patients showed improvement in skin lesions, allowing reductions or discontinuation of baseline immunosuppressive therapies like methotrexate and prednisone.
- The treatment was well tolerated without serious adverse events reported over the study period.
- The success of tofacitinib suggests that inhibition of the JAK-STAT pathway, particularly associated with interferon gamma, plays a critical role in addressing the inflammation in both sarcoidosis and granuloma annulare.
- Granuloma annulare patients also responded positively to JAK inhibitors, highlighting their potential in dermatologic inflammatory conditions.
- There is strong interest in further controlled studies for both sarcoidosis and granuloma annulare to validate these preliminary findings.
- Damsky et al. New Engl J Med 2018
- Damsky et al. J Am Acad Dermatol 2020
- Damsky et al. Nature Communications 2022
- Clark et al. Br J Dermato 2023; 188: 134-154
- Wang et al. J All Clin Immunol 2020
- Peterson et al. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib
- Damsky et al. Nature Communications in press