ZEPOSIA (ozanimod (chlorhydrate d')) - Rectocolite hémorragique (RCH)

Key points

Unfavourable opinion for reimbursement in the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.

Role in the care pathway?

The objectives of medicinal treatment are first to induce remission and then to maintain corticosteroid-free remission and improve quality of life.

The choice of treatment is governed, in particular, by the severity of the disease and the extent of colon damage. As second-line treatment of moderately to severely active UC in adult patients who have had an inadequate response to the conventional treatment, or for whom this treatment is contraindicated or poorly tolerated, TNF inhibitors (infliximab, adalimumab and golimumab) are the reference treatment. As second-line treatment, ENTYVIO (vedolizumab) represents an alternative to TNF inhibitors. However, a TNF inhibitor should be preferred to vedolizumab in two specific clinical situations:

• in the event of extra-intestinal manifestations (rheumatic, cutaneous and ocular manifestations, in particular), given the local action mechanism of vedolizumab;
• with infliximab being the recommended biologic therapy in the event of severe acute colitis (expert opinion).

As third-line treatment, in addition to the above treatments not yet used, the alternatives are a JAK inhibitor, tofacitinib (XELJANZ) and an IL-12/23 inhibitor, ustekinumab (STELARA). However, in patients over 65 years of age, smokers or former smokers, patients with other cardiovascular risk factors and patients with other cancer risk factors, tofacitinib should only be used if no other appropriate therapeutic alternative is available. “In the completed clinical trial (A3921133) in patients with rheumatoid arthritis (RA) aged 50 years or over and with at least one additional cardiovascular risk factor, an increase in the incidence of myocardial infarction was observed in comparison with TNF-alpha inhibitors. The trial also demonstrated an increase in the incidence of malignant tumours, excluding non-melanoma skin malignancies (NMSM), in particular lung cancer and lymphoma, with tofacitinib compared to TNF-alpha inhibitors. Prescribers should discuss the risks associated with the use of XELJANZ with their patients, in particular myocardial infarction, lung cancer and lymphoma.” (See Letter to healthcare professionals, 07/07/2021). The SPC, which was updated at the end of 2021, specifies that in ulcerative colitis (UC) “in the UC ongoing extension trial, cases of PE and DVT have been observed in patients using tofacitinib 10 mg twice daily and with underlying VTE risk factor(s).”

Role of the medicinal product in the care pathway

In moderately to severely active UC in adult patients who have had an inadequate response, lost response, or were intolerant to conventional therapy, considering the absence of clinical data enabling the therapeutic benefit of ozanimod (ZEPOSIA) to be determined compared to:

• firstly, TNFα inhibitors (infliximab, adalimumab and golimumab) and vedolizumab (ENTYVIO),
• and secondly ustekinumab (STELARA) and tofacitinib (XELJANZ),

and, taking into account the modest effect size determined in comparison with placebo in patients with a globally moderate form of UC, and the safety profile of ozanimod,

the Committee deems that the role of ozanimod (ZEPOSIA) in the care pathway has not been determined.