Table 3.

Definite or probable cases of gastrointestinal perforations in the tofacitinib program.

Patient Age/sexTofacitinib DoseEventLocation of Perforation/surgeryConcomitant MedicationsOnset Study Day/outcomeRelated Factors
52/female3 mg twice daily + MTXGastric ulcer perforationUpper GI/simple gastrectomyPrednisolone, methotrexate, diclofenac, rabeprazoleDay 19/recoveredPeritonitis was also presented, had prior recurrent gastric ulcer, smoking for 17 years, and NSAID/low-dose steroid use.
58/female5 mg twice daily + MTXDiverticulitis and diverticular perforationLower GI/hemicolectomyPrednisone, methotrexate, acetylsalicylic acid, diclofenac, omeprazoleDay 815/recoveredDiverticulitis was also presented. Perforation confirmed by pathology report.
46/male5 mg twice daily + MTXAppendicitisLower GI/retrocecal appendectomyPrednisone, methotrexateDay 664/deathAscending colon necrosis was also presented. Fourteen days delayed treatment for appendicitis and subsequently developed septicemia and cardiac and respiratory arrest.
55/female5 mg twice daily + MTXDiverticulitis and intestinal perforationLower GI/resection of sigmoidMethylpresnisolone, methotrexate, nimesulide, omeprazoleDay 551/recovered
59/female5 mg twice daily + MTXAbdominal abscessLower GI/laparatomy omentectomy, transversectomyMethylprednisolone, aceclofenac (previous medication)Day 447/recoveredPeritoneal infection was also presented.
59/male10 mg twice daily + MTXDiverticular perforationLower GI/sigmoid colon resectionPrednisone, methotrexate, aspirinDay 362/recoveredHistory of severe diverticulosis. Abscess intestinal was also presented.
52/female10 mg twise daily + MTXPeritonitis and appendicitisLower GI/appendectomyMethylprednisolone, methotrexate, omeprazoleDay 45/recoveredHistory of diverticulum. Abscess was also presented.
62/female10 mg twice daily + MTXDiverticular perforationLower GI/colostomyMethylprednisolone, methotrexateDay 128/recovering
62/female10 mg twice daily + MTXPeridiverticular abscessUpper GI/sigmoid resectionPrednisone, meloxicam, methotrexate, cortisone injection, pantoprazole, omeprazoleDay 950/recoveredPossibly secondary to the previous event of sigmoid colitis with Clostridium difficile infection; aspiration of abscesses was carried out.
61/female10 mg twice daily + MTXPeritonitisLower GI/unspecified surgeryPrednisone, hydroxychloroquine, methotrexate, ketoprofen, deflazacortDay 357/recoveredClassic symptoms of acute appendicitis. CT and surgery reports described in the narrative confirmed perforation.
66/female10 mg twice daily + MTXDiverticular perforationLower GI/laparoscopyMethotrexate, celecoxibDay 63/recoveredConfirmed by surgical report and pathology report.
  • CT: computed tomography; GI: gastrointestinal; MTX: methotrexate; NSAID: nonsteroidal antiinflammatory drugs.