Tofacitinib for the Treatment of Tumor Necrosis Factor-α Inhibitor Refractory Esophageal Crohn's Disease

A Case Report

Sunina Nathoo; William A. Hood; Sara Keihanian; Amy L. Collinsworth; Sarah C. Glover


J Med Case Reports. 2016;10(264) 

In This Article

Case Presentation

A 67-year-old Caucasian woman with a history of small and large bowel CD presented with new dysphagia. She was diagnosed with CD at age 30. Her disease had been complicated by fistula formation and multiple small bowel resections, as well as small intestinal bacterial overgrowth, chronic diarrhea, and osteoporosis. At the time of presentation, she had been on adalimumab (40 mg every other week) and mesalamine for 2 years. Previous medications included 6-mercaptopurine, azathioprine, methotrexate, infliximab, prednisone, and budesonide. She was not on a proton pump inhibitor at the time. Her vital signs were all within normal limits and her physical examination was unremarkable.

An upper endoscopy was performed and revealed deep linear ulcerations throughout the majority of her esophagus (Fig. 1) with a normal stomach and duodenum. Esophageal biopsies showed lymphocytic esophagitis characterized by dense lymphoplasmacytic infiltrates within the mucosa and lamina propria and an ill-formed granulomatous reaction consistent with an esophageal manifestation of CD (Fig. 2). Results from staining for acid-fast organisms with acid-fast bacillus (AFB) stain were negative and no viral cytopathic effects or intra-cellular inclusions were found. Our patient also had negative results in an interferon-gamma (IFN-γ) release assay, no remarkable findings on a chest X-ray, and computed tomography enterography that was negative for any intraluminal masses.

Figure 1.

Endoscopic findings of longitudinal, serpiginous ulcerations along the entirety of the esophagus consistent with an esophageal manifestation of Crohn's disease. Our patient was on adalimumab and mesalamine at the time

Figure 2.

Esophageal biopsies from an initial endoscopy that show granulomatous changes on low (left) and high (right) magnification

Our patient was subsequently started on a budesonide suspension but had an inadequate clinical response after 5 months. Thus, adalimumab was increased to 40 mg every week. A repeat endoscopy showed mid-esophageal ulcerations that were biopsied. Examination of the specimens demonstrated inflamed granulation tissue and inflammatory exudate. Immunohistochemical stains of the biopsy specimens were negative for herpes simplex virus and cytomegalovirus. At this point, omeprazole 40 mg once daily was started, but her symptoms persisted despite intensified TNF-α inhibitor therapy and concurrent proton pump inhibitor use. Adalimumab was thus stopped. Tofacitinib 5 mg twice daily was started after consideration of both ustekinumab and a drug trial involving an interleukin (IL) 6 inhibitor. Ustekinumab use was precluded by insurance and cost. Vedolizumab had not yet been approved for clinical use.

Six months later our patient was seen in a follow-up appointment and had no esophageal symptoms. A repeat endoscopy with biopsies was performed 7 months after she started taking tofacitinib. This study demonstrated esophageal scarring and nonspecific chronic inflammation in her distal esophagus, but showed complete resolution of her previous ulcerative disease (Fig. 3). Biopsies demonstrated that her mucosa showed no significant granulomatous changes as were previously found (Fig. 4). A repeat endoscopy 2 years after tofacitinib initiation was unremarkable and she did not experience any adverse events.

Figure 3.

Repeat endoscopy shows healed esophageal mucosa following initiation of tofacitinib

Figure 4.

Esophageal biopsies after treatment that show a normal esophagus without significant alteration on low (left) and high (right) magnification