Table 3.

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

Patient Age/sex	Tofacitinib Dose	Event	Location of Perforation/surgery	Concomitant Medications	Onset Study Day/outcome	Related Factors
52/female	3 mg twice daily + MTX	Gastric ulcer perforation	Upper GI/simple gastrectomy	Prednisolone, methotrexate, diclofenac, rabeprazole	Day 19/recovered	Peritonitis was also presented, had prior recurrent gastric ulcer, smoking for 17 years, and NSAID/low-dose steroid use.
58/female	5 mg twice daily + MTX	Diverticulitis and diverticular perforation	Lower GI/hemicolectomy	Prednisone, methotrexate, acetylsalicylic acid, diclofenac, omeprazole	Day 815/recovered	Diverticulitis was also presented. Perforation confirmed by pathology report.
46/male	5 mg twice daily + MTX	Appendicitis	Lower GI/retrocecal appendectomy	Prednisone, methotrexate	Day 664/death	Ascending colon necrosis was also presented. Fourteen days delayed treatment for appendicitis and subsequently developed septicemia and cardiac and respiratory arrest.
55/female	5 mg twice daily + MTX	Diverticulitis and intestinal perforation	Lower GI/resection of sigmoid	Methylpresnisolone, methotrexate, nimesulide, omeprazole	Day 551/recovered
59/female	5 mg twice daily + MTX	Abdominal abscess	Lower GI/laparatomy omentectomy, transversectomy	Methylprednisolone, aceclofenac (previous medication)	Day 447/recovered	Peritoneal infection was also presented.
59/male	10 mg twice daily + MTX	Diverticular perforation	Lower GI/sigmoid colon resection	Prednisone, methotrexate, aspirin	Day 362/recovered	History of severe diverticulosis. Abscess intestinal was also presented.
52/female	10 mg twise daily + MTX	Peritonitis and appendicitis	Lower GI/appendectomy	Methylprednisolone, methotrexate, omeprazole	Day 45/recovered	History of diverticulum. Abscess was also presented.
62/female	10 mg twice daily + MTX	Diverticular perforation	Lower GI/colostomy	Methylprednisolone, methotrexate	Day 128/recovering
62/female	10 mg twice daily + MTX	Peridiverticular abscess	Upper GI/sigmoid resection	Prednisone, meloxicam, methotrexate, cortisone injection, pantoprazole, omeprazole	Day 950/recovered	Possibly secondary to the previous event of sigmoid colitis with Clostridium difficile infection; aspiration of abscesses was carried out.
61/female	10 mg twice daily + MTX	Peritonitis	Lower GI/unspecified surgery	Prednisone, hydroxychloroquine, methotrexate, ketoprofen, deflazacort	Day 357/recovered	Classic symptoms of acute appendicitis. CT and surgery reports described in the narrative confirmed perforation.
66/female	10 mg twice daily + MTX	Diverticular perforation	Lower GI/laparoscopy	Methotrexate, celecoxib	Day 63/recovered	Confirmed by surgical report and pathology report.

CT: computed tomography; GI: gastrointestinal; MTX: methotrexate; NSAID: nonsteroidal antiinflammatory drugs.