New-Onset Ulcerative Colitis Associated to Ixekizumab

Background:
Ixekizumab is a monoclonal antibody that binds interleukin 17A (IL-17A) cytokine selectively and inhibits interaction with its receptor. This humanized monoclonal antibody is approved for the treatment of ankylosing spondylitis, non-radiographic axial spondyloarthritis, psoriatic arthritis and plaque psoriasis. Most common adverse reactions associated with this drug include injection site reactions, upper respiratory tract infections, nausea, and fungal infections. Development or exacerbations of inflammatory bowel diseases (IBD) is a rare adverse reaction of this medication. We report a case of new-onset ulcerative colitis in a 76-year-old man on ixekizumab for plaque psoriasis.
Methods:
This is the case of a 76-year-old man with past medical history of chronic plaque psoriasis of more than 20 years previously on methotrexate who initially presented with complaints of abdominal pain, anorexia, unintentional weight loss of 40 lbs. and watery diarrhea that later progressed to bloody. The patient denied having similar symptoms in the past. The patient had started ixekizumab 2 months prior to presentation, which was discontinued. Fecal calprotectin at the time was elevated >8000 mcg/g. Abdominal/pelvic CT with contrast was remarkable for concentric mural thickening of the distal transverse colon, descending colon, sigmoid colon, and proximal rectal region with surrounding fat stranding and associated mesenteric lymphadenopathy. Colonoscopy showed continuous marked erythema with associated ulcerations, exudates and loss of vascular pattern starting from distal descending (approx. 45 cm from anal verge) through sigmoid and rectum. The patient was admitted and started on steroids and initial dose of infliximab. The patient was discharged on steroid taper but had allergic reaction to the next infliximab dose. The patient was changed to upadacitinib and tapered off steroids with an adequate response.
Results:
In clinical trials, during the 12-week, placebo-controlled period, ulcerative colitis (0.2%) and Crohn’s disease (0.1%) occurred at a greater frequency in the ixekizumab 80 mg Q2W group than the placebo group (0%) in subjects with plaque psoriasis. A retrospective analysis demonstrated that IL-17 inhibitors are associated with new onset of IBD or exacerbations within 6 months of therapy.
Conclusions:
In this case, our patient did not have previous symptoms that suggested IBD, we hypothesize that he developed de novo ulcerative colitis associated with IL-17A inhibitor, ixekizumab. Although a rare adverse reaction, physicians should be aware of the potential association between exposure to anti-IL-17 and exacerbation or induction of IBD. All patients should be oriented about this adverse reaction and be counseled to monitor for new or worsening abdominal symptoms.