Ozanimod: A Practical Review for Nurses and Advanced Practice Providers

Figures & data

Figure 1 Potential mechanism of action of ozanimod in inflammatory bowel disease. Binding of ozanimod induces S1P₁ receptor internalization, blocking the capacity of lymphocytes to egress from lymphoid tissue into circulation.^5,7,8 The mechanism by which ozanimod exerts therapeutic effects in inflammatory bowel disease is unknown but may involve the reduction of lymphocyte migration into, or direct effects on, the gut.⁵ Although S1P is prominent throughout the bloodstream, it is not depicted in the bloodstream on the left for simplicity in this conceptual illustration. ^aIncluding T cells and B cells. ^bInnate immune cells, which are responsible for antigen presentation and immunosurveillance, include macrophages, monocytes, and natural killer cells, among others. Adapted from Sands BE, Schreiber S, Blumenstein I, Chiorean MV, Ungaro RC, Rubin DT. Clinician’s guide to using ozanimod for the treatment of ulcerative colitis. J Crohns Colitis. 2023;jjad112. Creative Commons.⁹

Abbreviation: S1P, sphingosine 1-phosphate.

Table 1 Adverse Events in Patients with UC in the Phase 3 True North study¹⁵

Event	Induction Period			Maintenance Period
	Cohort 1		Cohort 2
	Placebo (n = 216)	Ozanimod 0.92 mg (n = 429)	Ozanimod 0.92 mg (n = 367)	Placebo (n = 227)	Ozanimod 0.92 mg (n = 230)
Any AE, n (%)	82 (38.0)	172 (40.1)	146 (39.8)	83 (36.6)	113 (49.1)
Serious AE, n (%)	7 (3.2)	17 (4.0)	23 (6.3)	18 (7.9)	12 (5.2)
Related serious AE	2 (0.9)	1 (0.2)	3 (0.8)	1 (0.4)	0
AE leading to discontinuation, n (%)	7 (3.2)	14 (3.3)	14 (3.8)	6 (2.6)	3 (1.3)
AEs occurring in ≥3% patients receiving ozanimod during induction or maintenance, n (%)
Anemia	12 (5.6)	18 (4.2)	16 (4.4)	4 (1.8)	3 (1.3)
Nasopharyngitis	3 (1.4)	15 (3.5)	10 (2.7)	4 (1.8)	7 (3.0)
Headache	4 (1.9)	14 (3.3)	10 (2.7)	1 (0.4)	8 (3.5)
Increased ALT	0	11 (2.6)	6 (1.6)	1 (0.4)	11 (4.8)
Arthralgia	3 (1.4)	10 (2.3)	5 (1.4)	6 (2.6)	7 (3.0)
Increased GGT	0	5 (1.2)	6 (1.6)	1 (0.4)	7 (3.0)

Notes: From Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280–1291. Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.¹⁵

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; UC, ulcerative colitis.

Table 2 Incidence of Adverse Events of Special Interest in Patients with UC and MS Treated with Ozanimod 0.92 mg^6,15

Event	UC		MS^c (n = 882)
	Induction^a (n = 496)	Maintenance^b (n = 230)
Infections, %	9.9	23.0	35.0
Serious infections	0.8	0.9	1.0
Herpes zoster	0.4	2.2	0.6
Lymphopenia (ALC <0.2 x 10^9), %	2.0	2.3	3.3
Bradyarrhythmia and AV conduction delays, %
Bradycardia	Day 1: 0.2	None	Day 1: 0.6
	After day 1: 0.2	NR	After day 1: 0.8
AV conduction delays	None^d		None^d
Hypertension, %	1.2	1.7	3.9
Hepatic transaminase/LFT elevation, %
ALT ≥3 x ULN	2.6^e	3.0	5.5
ALT ≥5 x ULN	0.9^e	0.9	1.6
Macular edema, %	0.2	0.4	0.3
Respiratory effects
FEV1 reductions^f
Mean difference (mL)	22^e	NR	60
% predicted	0.8^e	NR	1.9
FVC reductions^g
Mean difference (mL)	44^e	NR	60
% predicted	0.5^e	NR	1.4
Malignancy, %	0^e	0.9^h	1.4^i

Notes: ^aEvaluated in the induction period of two randomized, double-blind, placebo-controlled trials (phase 2 TOUCHSTONE and phase 3 True North) unless otherwise specified. ^bEvaluated in the maintenance period of the phase 3 True North trial. ^cEvaluated in two randomized, double-blind, double-dummy, parallel-group, active comparator–controlled trials (phase 3 SUNBEAM and RADIANCE) unless otherwise specified. ^dNo Mobitz type II second-degree or third-degree AV blocks were reported in patients with dose titration. ^ePercentages were calculated from the induction period of the phase 3 UC trial (True North) only (double-blind ozanimod, n = 429). ^fFor MS, reductions on ozanimod compared with interferon beta and measured at 12 months; for UC, reductions on ozanimod compared with placebo and measured at 10 weeks. ^gFor MS, reductions on ozanimod compared with interferon beta and measured at 3 months; for UC, reductions on ozanimod compared with placebo and measured at 10 weeks. ^hIncluding 1 basal cell carcinoma and 1 rectal adenocarcinoma. ⁱData from a pooled analysis of patients with MS who received ozanimod 0.46 mg or 0.92 mg beginning during any four of the phase 1–3 parent trials and continuing into the subsequent OLE (n = 2787); included 13 nonmelanoma skin cancers, 1 melanoma, and 24 noncutaneous malignancies.

Abbreviations: ALC, absolute lymphocyte count; ALT, alanine aminotransferase; AV, atrioventricular; FEV₁, forced expiratory volume over 1 second; FVC, forced vital capacity; LFT, liver function test; MS, multiple sclerosis; NR, not reported; OLE, open-label extension; UC, ulcerative colitis; ULN, upper limit of normal.

Figure 2 Mean ALC over time in the induction and maintenance periods of the True North study in patients with UC.²⁴ Patients who received continuous placebo (placebo) had stable levels of mean ALC over time, remaining within the normal range (1.02–3.36 × 10⁹/L). Patients who continuously received ozanimod during the induction and maintenance periods (ozanimod/ozanimod) had sustained ALC reductions over time, which began to recover within 8 weeks in patients who discontinued ozanimod during the maintenance period (ozanimod/placebo). Error bars denote standard error. Reprinted from Sands BE, Schreiber S, Blumenstein I, Chiorean MV, Ungaro RC, Rubin DT. Clinician’s guide to using ozanimod for the treatment of ulcerative colitis. J Crohns Colitis. 2023;jjad112. Creative Commons.⁹

Abbreviations: ALC, absolute lymphocyte count; UC, ulcerative colitis.

Table 3 Checklist for Ozanimod Treatment in Patients with UC

Indication^Citation6
□ Moderately to severely active UC □ Age 18 or older □ No requirement of prior UC treatment
Contraindications^Citation6
□ Experienced MI, unstable angina, stroke, transient ischemic attack, decompensated HF requiring hospitalization, or NYHA class III/IV HF in the last 6 months □ Presence of Mobitz type II second- or third-degree AV block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker □ Severe untreated sleep apnea □ Current use of an MAO inhibitor
Pre-testing Assessments^Citation6
□ ECG and □ CBC (within 6 months or after discontinuation of prior UC therapy) □ Assess for active infection □ Test for VZV antibodies without vaccine documentation or healthcare professional confirmed history of chickenpox  ○ Administer VZV vaccine in antibody-negative patients ≥1 month prior to treatment □ Ophthalmic evaluation (history of macular edema or high-risk patients) □ Transaminase and bilirubin levels (within 6 months) □ Assess for current or prior medication use that may  ○ Increase immunosuppressive effect  ○ Slow heart rate or AV conduction
Routine Monitoring
□ Monitor adverse events throughout treatment □ Monitor BP (patients with preexisting hypertension can monitor weekly at home for the first month; then BP should be monitored 3 months after treatment initiation and then every 6 months thereafter regardless of preexisting hypertension)^Citation6,Citation9 □ Monitor for signs of infection throughout treatment and continuing for 3 months after discontinuation^Citation6 □ Monitor for signs of PML, cryptococcal meningitis, and PRES throughout treatment^Citation6 □ Monitor ALC every 3 months^Citation9 □ Monitor for changes in vision or symptoms of macular edema in all patients and perform regular ophthalmic evaluation in patients with diabetes mellitus or history of uveitis^Citation6 □ Monitor for symptoms of hepatic dysfunction and assess liver enzymes periodically (at 1, 3, 6, 9, and 12 months after treatment initiation and then every 3 months thereafter)^Citation6,Citation9 □ Spirometric evaluation (if clinically indicated)^Citation6 □ Monitor the efficacy of ozanimod regularly  ○ Monitor symptoms at clinic visits 3-, 6-, and 12-months post-treatment initiation and then every 6–12 months thereafter; patients should report any symptom changes between visits  ○ Evaluate inflammatory biomarkers (eg, CRP, FCP) and perform IUS 3 months post-treatment initiation  ○ Perform endoscopy and histology assessments or IUS 6- and 12-months post-treatment initiation and then every 6–12 months thereafter
Most Commonly Occurring Side Effects^Citation6
□ Upper respiratory tract infections  □ Urinary tract infection	□ Elevated liver enzymes □ Back pain □ Hypertension		□ Orthostatic hypotension □ Headache
Potential Serious Side Effects^Citation6
□ Infection		□ Macular edema
□ PML		□ Hepatic dysfunction/liver injury
□ Bradyarrhythmia  □ Hypertension  □ Shortness of breath		□ PRES
Potential Drug/Food Interactions^Citation6
□ Anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies □ Anti-arrhythmic (class Ia or III), QT-prolonging, or HR-lowering therapies □ Adrenergic/serotonergic therapies (eg, opioids, SNRIs, SSRIs) □ Beta blockers and calcium channel blockers □ MAO inhibitors □ Strong CYP2C8 inhibitors and inducers □ Foods with high amounts of tyramine (aged, fermented, cured, smoked, and pickled foods)
Vaccination Guidelines^Citation6
□ Do not administer live vaccines 1 month prior to initiating ozanimod and 3 months after discontinuing ozanimod □ Vaccine efficacy may be reduced with ozanimod
Key Patient Education Information^Citation6
□ Ozanimod should be taken once a day with or without food (patients with mild to moderate hepatic impairment [Child-Pugh class A or B] should adjust the dose to once every other day) □ The ozanimod dose must be gradually increased during the first week of treatment to reduce bradycardia risk □ Patients who miss 1 or more days of ozanimod during the first 14 days of treatment should inform their healthcare provider; ozanimod may need to be re-initiated □ Patients who miss a dose after the first 14 days of treatment can take the next scheduled dose □ Women of childbearing potential should use effective contraception during therapy and for 3 months after ozanimod discontinuation; they should inform their healthcare provider right away if they become pregnant while taking ozanimod or within 3 months of discontinuing ozanimod □ Patients should inform their healthcare provider if they are breastfeeding or plan to breastfeed, as it is unknown if ozanimod passes into breast milk □ Patients should contact their healthcare provider right away if they have serious side effects, such as symptoms of infection (including PML), slow heart rate, liver problems, increased blood pressure, breathing problems, vision problems, or symptoms of PRES

Note: This table is not comprehensive of all parameters within the prescribing information.

Abbreviations: ALC, absolute lymphocyte count; AV, atrioventricular; BP, blood pressure; CBC, complete blood count; CRP, C-reactive protein; ECG, electrocardiogram; FCP, fecal calprotectin; HF, heart failure; HR, heart rate; IUS, intestinal ultrasound; MAO, monoamine oxidase; MI, myocardial infarction; NYHA, New York Heart Association; PML, progressive multifocal leukoencephalopathy; PRES, posterior reversible encephalopathy syndrome; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; UC, ulcerative colitis; VZV, varicella zoster virus.

Figure 3 Guide to establishing suitability for ozanimod treatment in patients with UC.⁶ Ozanimod may be suitable for adult patients with moderately to severely active UC. The ideal patient has lost response or failed to respond to conventional or advanced therapies. Patients must pass preinitiation assessments as described in the US prescribing information. Consultation with a cardiologist is recommended prior to treatment initiation in patients with preexisting cardiac conditions. Caution is advised for patients at risk for macular edema and those taking immunosuppressive drugs. The prescribing information also outlines patients for whom ozanimod is contraindicated or not recommended. This figure outlines the key issues but is not comprehensive of all considerations detailed in the prescribing information.

Abbreviations: 5-ASA, 5-aminosalicylic acid; AV, atrioventricular; CBC, complete blood count; ECG, electrocardiogram; HF, heart failure; JAK, Janus kinase; MAO, monoamine oxidase; MI, myocardial infarction; NYHA, New York Heart Association; UC, ulcerative colitis; VZV, varicella zoster virus.

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