Extended tofacitinib use led to ‘complete’ clinical response in refractory celiac disease



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Key takeaways:

  • Tofacitinib for refractory celiac disease type 2 improved diarrhea/loose stools, abdominal pain and weight gain within 2 to 14 days.
  • An extended follow-up demonstrated persistent clinical remission over 2 years.

Tofacitinib “should be considered as a treatment option” for patients with refractory celiac disease type 2 who previously failed treatment with therapies such as budesonide, according to data in Clinical Gastroenterology and Hepatology.

“Refractory celiac disease type 2 is a rare condition with high mortality due to a lack of effective treatment strategies,” Tessa Dieckman, MD, of the department of immunology at Leiden University Medical Center, and colleagues wrote. “In a previous in vitro study, we demonstrated the potential of tofacitinib, a small-molecule Janus kinase 2/3 inhibitor, to control activity of the aberrant intraepithelial lymphocyte population.”



Within 2 to 14 days of per-protocol analysis, tofacitinib led to a “prompt resolution” of: Image: digestive tract •	diarrhea/loose stools •	disappearance of abdominal pain  •	weight gain

Data derived from: Dieckman T, et al. Clin Gastroenterol Hepatol. 2024;doi:10.1016/j.cgh.2024.05.022.

In an open-label, prospective pilot study, researchers in the Netherlands treated four patients with refractory celiac disease type 2 — all of whom had failed previous treatment with corticosteroids, cladribine or autologous bone marrow transplantation — with tofacitinib 10 mg twice daily for 12 weeks. Of these, one patient at week 8 had a dose modification to 5 mg twice daily. Two additional patients in Germany who fulfilled inclusion criteria received treatment outside of protocol.

Researchers noted that all patients had at least 20% aberrant intraepithelial lymphocytes on flow cytometry, with a median 70% to 90% aberrant cells.

The primary immunological endpoint was an absolute decrease of at least 20% in aberrant intraepithelial lymphocytes from baseline to week 12 and the secondary endpoint was improvement in histology scores.

According to study results, tofacitinib led to a “prompt resolution” of diarrhea/loose stools, disappearance of abdominal pain and weight gain (median increase, 12.3%) within 2 to 14 days in the per-protocol group. Although symptoms recurred upon treatment discontinuation, reinstitution led to a “rapid and complete” clinical response, researchers reported, with similar results in the off-protocol group.

Patients did not achieve the primary endpoint, as the median fraction of aberrant intraepithelial lymphocytes at week 12 was 72%. However, at week 12 four of the six patients experienced mucosal improvement and two patients in the per-protocol group demonstrated similar histological scores.

Data from extended follow-up showed clinical remission persisted over 2 years among the six patients, with a median weight gain of 19.8%. In addition, histological scores further improved without changes in the number of aberrant cells.

Researchers reported 52 adverse events, with one patient from the per-protocol group experiencing two serious adverse events.

“This small study size warrants cautious interpretation,” Dieckman and colleagues wrote. “The consistent clinical responses, rapid recurrence of symptoms after discontinuation and the effectiveness of reinstitution of therapy with extensive follow-up add to the robustness of our observations.”

They continued: “We feel that tofacitinib should be considered as a treatment option for patients who fail open-capsule budesonide therapy. We anticipate that this study will change the future treatment landscape of refractive celiac disease type 2.”

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