AS A HOSPITAL PHARMACIST, you will hear more about treating patients hospitalized with ACUTE severe ulcerative colitis due to updated guidelines. Up to 1 in 4 ulcerative colitis patients will be hospitalized for a severe flare. This includes 6 or more bloody stools/day PLUS at least one systemic sign like fever, anemia, elevated C-reactive protein (CRP), etc. Follow these simple steps...
Rule out Clostridium difficile. It can mimic an ulcerative colitis flare and is associated with increased mortality in these patients. Assess for triggers, such as NSAIDs, recently started mesalamine or another aminosalicylate, or nonadherence to maintenance medications.
Start with IV methylprednisolone (Solu-Medrol) 60 mg/day or hydrocortisone (Solu-Cortef) 300 to 400 mg/day (as 100 mg 3 or 4 times daily). There's no evidence higher steroid doses are better. Add rectal steroids if needed for additional relief. Transition IV steroids to oral (e.g., prednisone) in 3 days if the patient responds. Look for improved vital signs, decreased pain or CRP, fewer stools, etc. But IV steroids won't work in about one-third of patients.
If there's no improvement in 3 to 5 days, add rescue infliximab (Remicade) 5 mg/kg (some experts suggest 10 mg/kg) at times 0, 2, and 6 weeks, followed by maintenance therapy every 8 weeks OR IV cyclosporine (Sandimmun Neoral) 2 or 2.5 mg/kg/day and may increased to 4 mg/kg/day (Doses are adjusted to maintain target trough concentrations of about 200 to 250 ng/mL) to try to avoid a colectomy. They seem equally effective. But lean away from cyclosporine (Sandimmun Neoral) in patients who failed an outpatient immunomodulator, such as azathioprine (Imuran) or mercaptopurine (Puri-nethol).
| Table (1). Common Medical Therapies for Patients with Ulcerative Colitis | ||
|---|---|---|
| MEDICATION | DAILY DOSAGE | COMMON SIDE EFFECTS |
| Sulfasalazine | 2 to 6 g | Agranulocytosis, diarrhea, headache, nausea, rash, renal impairment |
| Mesalamine (Asacol, Pentasa) |
Asacol, 2.4 to 4.8 g | |
| Pentasa, 2 to 4 g | ||
| Prednisone | 40 to 60 mg | Adrenal insufficiency, hyperglycemia, osteoporosis |
| Steroid enema | 100 mg | Diarrhea |
| Azathioprine (Imuran) | 1.5 to 2.5 mg per kg | Headache, diarrhea, hepatotoxicity, leukopenia, myalgias |
| Mercaptopurine (Purinethol) | 0.75 to 1.5 mg per kg | Headache, diarrhea, hepatotoxicity, leukopenia, myalgias |
| Infliximab (Remicade) | 5 mg per kg | Arthralgias, fever, infection, malaise, myalgias |
| An initial dose of infliximab 5 mg/kg is given (considered day one of infliximab therapy). Infusions require a dedicated IV line, a filter (1.2 micron or less), and should be given over at least 2 hours within 3 hours of reconstitution. If well tolerated, the same dose is repeated at 2 and 6 weeks. | ||
| Information from Am Fam Physician. 2007 Nov 1;76(9):1323-1330. | ||
- Who failed outpatient immunomodulators (e.g., azathioprine).
- With low albumin levels (e.g., < 2.3 g/dL).
- With low cholesterol or magnesium levels (these can increase the risk of neurotoxicity with cyclosporine).
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Cyclosporine should be infused slowly (over a minimum of 2 to 6 hours) to reduce the risk of adverse effects (e.g., acute nephrotoxicity, flushing, nausea). Cyclosporine is usually given as a continuous infusion, as the IV solution remains stable for up to 24 hours.
Don't routinely add antibiotics. They don't seem to improve outcomes in most cases. Save antibiotics for patients at high risk of infection, such as those with sepsis, toxic megacolon, or perforated colon. Try to avoid opioids or anticholinergics, since slowing the gut may increase the risk of toxic megacolon.
Work with the GI specialist to transition to outpatient treatment. For example, anticipate discharging on prednisone (Solupred) 40 mg/day for 2 to 3 months then tapers the dose by 5 mg per week to a daily dose of 20 mg. Then further tapers the dose by 2.5 to 5 mg per week, until prednisone (Solupred) is discontinued. And infliximab (Remicade) patients will need their next dose 2 weeks after the first. Verify all patients have a follow-up appointment within about 1 week.
REFERENCES
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Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019 Mar;114(3):384-413. Available at: https://journals.lww.com/ajg/Fulltext/2019/03000/ACG_Clinical_Guideline__Ulcerative_Colitis_in.10.aspx
Burri E, Maillard MH, Schoepfer AM, Seibold F, Van Assche G, Rivière P, Laharie D, Manz M; Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology. Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update. Digestion. 2020;101 Suppl 1:2-15. Available at: https://www.karger.com/Article/FullText/504092
Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Nachury M, Moreau J, Delchier JC, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Dupas JL, Carbonnel F, Bommelaer G, Coffin B, Roblin X, Van Assche G, Esteve M, Färkkilä M, Gisbert JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lémann M; Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1909-15. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61084-8/fulltext
Whaley KG, Rosen MJ. Contemporary Medical Management of Acute Severe Ulcerative Colitis. Inflamm Bowel Dis. 2019 Jan 1;25(1):56-66. Available at: https://academic.oup.com/ibdjournal/article/25/1/56/5034511#126834985