Growing armamentarium of therapies for IBD has ‘truly revolutionized’ care
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LAS VEGAS — A presenter at the Crohn’s & Colitis Congress outlined some of the newer therapies that have expanded the current “arsenal of tools” for the treatment of inflammatory bowel disease.
“When we think about these therapies, we know that they have truly revolutionized our management of patients with inflammatory bowel disease,” David Choi, PharmD, clinical pharmacy specialist and associate director at the University of Chicago Inflammatory Bowel Disease Center, said. “The landscape really has improved, and more and more therapies have come to market. ... But I think sometimes we can be a little hesitant to use some of these newer therapies, because there’s a lot of unknown about it. So, you stick with what you’re comfortable with.”
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Newer therapies for IBD include sphingosine 1-phosphate (S1P) receptor modulators, Janus kinase (JAK) inhibitors and interleukin-23 (IL-23) inhibitors. Here, Choi discussed mechanisms of action, contraindications and side effects for each.
S1P receptor modulators
Ozanimod is an S1P receptor modulator approved for the treatment of patients with ulcerative colitis. It is dosed at 0.23 mg daily on days 1 through 4, 0.46 mg daily on days 5 through 7 and 0.92 mg daily thereafter.
“With that dose titration, patients cannot miss a dose in the first 2 weeks,” Choi noted. “If they miss a dose in the first 2 weeks, you have to redo that dose titration all over again.”
Etrasimod is another S1P receptor modulator approved for the treatment of UC and is dosed at 2 mg daily. Both ozanimod and etrasimod reduce circulating lymphocytes.
Key contraindications for these S1Ps include cardiovascular events in the last 6 months, sick sinus syndrome and severe untreated sleep apnea, among others. While largely well-tolerated, side effects include transient dose dependent bradycardia and hypertension.
Prior to drug administration, patients should undergo baseline electrocardiogram, ophthalmologic exam for patients with diabetes or uveitis, complete blood count and liver function tests (LFTs), as well as have documented immunity to varicella zoster virus. Patients also should receive a baseline skin examination prior to etrasimod administration, Choi noted. Maintenance CBC and LFTs are recommended every 3 to 6 months for both therapies.
JAK inhibitors
Upadacitinib is a JAK 1 selective enzyme inhibitor that prevents gene expression of cytokines and activity of immune cells. It is approved for use in both UC and Crohn’s disease at 45 mg daily for 8 and 12 weeks, respectively, followed by 15 mg or 30 mg daily.
In terms of side effects, upadacitinib has been linked to acne (20%-30%) but appears to be dose and age dependent, Choi said. Additional side effects include malignancy and dyslipidemia, as well as boxed warnings of thrombosis, infection and mortality, among others.
“The black box warning is probably the most important conversation to have with the patient,” Choi said. “Evaluating where it came from, the backstory in terms of how the warning got on there, what it really means and what patient population we really saw that for. I think it’s just really helpful to give context to that warning for patients to have that discussion.”
Monitoring includes testing for tuberculosis and viral hepatitis at baseline with potential for annual maintenance, a lipid panel at baseline and every 8 to 12 weeks then clinically as indicated, and CBC and LFTs at baseline and every 3 to 6 months.
Anti-IL-23s
Risankizumab and mirikizumab are recently approved for the treatment of patients with CD and UC, respectively. Risankizumab requires an IV loading dose of 600 mg on weeks 0, 4 and 8 and a subcutaneous maintenance dose of 360 mg at week 12, then every 8 weeks. Similarly, mirikizumab has an IV loading dose of 300 mg on weeks 0, 4 and 8 and a subcutaneous 200 mg maintenance dose every 4 weeks.
Both anti-IL-23s are well-tolerated, with possible side effects including injection-site reaction, nasopharyngitis and headache. Monitoring includes testing for tuberculosis and viral hepatitis, CBC and LFTs at baseline, with maintenance schedules similar to JAK inhibitors.
“I think it’s really exciting in the IBD space right now because our arsenal of tools is going to continue to grow,” Choi said. “There are many drugs in the pipeline right now, some of them are additional agents and drug classes that already exist, some of these are completely new mechanisms of action that will be beneficial for patients with inflammatory bowel disease.”
Perspective
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Katherine Falloon, MD
It certainly is an exciting time to be an IBD provider, as novel therapeutic options continue to come down the pipeline.
The past 3 years have seen the introduction of new oral options, including S1P receptor modulators and the selective JAK inhibitor upadacitinib, the first oral small molecule to be approved for both UC and Crohn’s disease. Selective anti-interleukins targeting both UC and CD also have been approved.
Ongoing study of these new agents is needed in a real-world setting to provide more insight into their efficacy and safety, as well as how they should be optimally positioned. Greater choice for patients and providers is critically important, and these therapies are a welcome addition to our IBD armamentarium.
Choi highlights the importance of a multidisciplinary team approach to the care of our patients with IBD and the key role that the IBD pharmacist has to play. Collaboration with IBD pharmacists can facilitate access to novel therapies for our patients in a way that is safe, effective and timely.
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Choi C, Kametas M. Medical therapy in IBD: Where to start, when to stay, how to choose. Presented at: Crohn’s & Colitis Congress; Jan. 25-27, 2024; Las Vegas.
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