Refractory Lymphocytic Colitis Treated With Upadacitinib

Background:
Microscopic colitis, further sub-divided as lymphocytic colitis and collagenous colitis is a chronic inflammatory disease of the colon with symptoms of chronic, watery, non-bloody diarrhea with normal or almost normal endoscopic findings. First-line treatment involves budesonide. Other lines of treatment include mesalamine, bismuth salicylate, and prednisone. For refractory cases, treatment options are scarce. Upadacitinib is a JAK1 inhibitor that has been approved for treatment of atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease. Here we present a case of refractory microscopic colitis treated with upadacitinib.
Methods:
Patient is a now 54-year-old woman who initially presented with diffuse abdominal pain and large volume watery diarrhea. She underwent a flexible sigmoidoscopy and biopsies diagnosed her with lymphocytic colitis. She had no exposure to implicated medications, and was a non-smoker. She was negative for celiac disease and was routinely tested for gastrointestinal pathogens. She was initially maintained on a course of budesonide 6 mg daily for about a year. However, her symptoms then worsened. She was trialed on multiple regimens including courses of rifaximin, loperamide, diphenoxylate/atropine, psyllium fiber, bismuth, eluxadoline, naltrexone, cholestyramine, colestipol, medical marijuana, and azathioprine to ameliorate her symptoms but with marginal success. After this, the decision was made to trial biologic therapy. She had an injection reaction after taking adalimumab, lost response to vedolizumab and had worsening of diarrhea with joint pains and pitting edema with ustekinumab.
Results:
Repeat sigmoidoscopy noted moderately edematous mucosa with scarring, erythema and inflammation in the distal transverse, descending and sigmoid colon with biopsies noting colonic mucosa with intraepithelial lymphocytosis, surface mucin loss and increased lamina propria with no cryptitis and architectural distortion consistent with her known history of lymphocytic colitis. Infectious stool studies were negative. CRP: 3.4 and Sed rate: 14. Given the findings despite multiple medical therapies, she was started on upadacitinib. Patient noted significant improvement in her symptoms with her bowel movements going from 15 + to 1 formed bowel movement a day.
Conclusions:
The treatment paradigm for microscopic colitis remains limited. Microscopic colitis is often associated with smoking, and certain medical therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), statins, selective serotonin reuptake inhibitors (SSRIs). Treatment often involves discontinuing the offending exposure, budesonide, and anti-diarrheal medication. For cases with only marginal improvement or intolerance to budesonide, options include mesalamine, bismuth salicylate, and prednisone. Literature has suggested the use of immunosuppressives including biologic therapy, specifically vedolizumab. Our patient had not only failed conventional therapy, but also multiple second-line therapies. This is the second report in the literature of lymphocytic colitis successfully being treated with upadacitinib. This case highlights another treatment for clinicians to consider in their therapeutic algorithm for refractory cases.