The Janus kinase (JAK) inhibitor tofactitinib that is used to treat autoimmune diseases such as ulcerative colitis and rheumatoid arthritis may also have potential as a treatment for coeliac disease, according to gastroenterologists in Europe.
Clinicians in Belgium have found that a man using tofactitinib to treat alopecia also had remission in a his celiac disease, despite eating a gluten-containing diet.
In a report published in Annals of Internal Medicine, Dr Lucas Wauters and colleagues from the Department of Gastroenterology at University Hospitals Leuven, describe the case of a young male patient who had coeliac disease and alopecia.
After achieving some remission from his coeliac disease, the 16-year old patient stopped his gluten-free diet after confirmation of clinical and serologic remission with only infiltrative lesions on duodenal biopsies. However showed relapse of severe small-intestinal damage after consuming gluten, but with no intestinal or extraintestinal symptoms. After discussing the risks and benefits, the patient decided not return to a gluten-free diet but to maintain watchful waiting.
The patient had also experienced alopecia from the age of 13 and started off-label use of tofacitinib, 5 mg twice daily, after he resumed eating gluten.
Follow-up investigations unexpectedly showed complete histologic and serologic remission of coeliac disease while he was still on a gluten-containing diet.
The patient continued tofacitinib use, with regular blood tests showing normal complete blood count, lipid levels, and creatine kinase levels.
The report authors noted that as a first generation JAK inhibitor, tofactinib interferes with the JAK-STAT signalling pathway for cytokines including Il-15. And because tofacitinib mainly inhibits JAK3 enzyme, it blocks CD8+ T-cell–mediated enteropathy.
They said the efficacy of tofacitinib in alopecia areata may be related to inhibition of CD8+ T-cell reactions to follicle associated autoantigens. They also noted that the abnormalities in cytokines such as IL-2, IL-8 and IL-10 are also thought to be implicated in the pathogenesis of coeliac disease.
“Despite promising results with tofacitinib in different autoimmune diseases, clinicians should be aware of the drug’s potential adverse effects, which include infections and abnormal lipid and creatine kinase levels,” they cautioned.
“Given the unmet need for non-dietary therapies, we believe that use of tofacitinib deserves further study in celiac disease, especially for refractory disease,” they added, noting that there is currently only one trial underway to investigate its effects in patients with refractory disease.