ENTYVIO

Key points

Favourable opinion for reimbursement in the following indications:

• treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist (second and third-line treatment);
• treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to conventional therapy and at least one tumour necrosis factor-alpha (TNFα) antagonist (third-line treatment).

Unfavourable opinion for reimbursement in the treatment of TNFα antagonist-naive adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to conventional therapy (second-line treatment).

What therapeutic improvement?

No clinical added value compared to intravenous vedolizumab (ENTYVIO 300 mg).

Role in the care pathway?

Treatment should be initiated and supervised by specialist healthcare professionals experienced in the diagnosis and treatment of ulcerative colitis or Crohn's disease.

Subcutaneous ENTYVIO 108 mg (vedolizumab) is intended to be a maintenance treatment. Patients should be given induction therapy with two IV injections of ENTYVIO 300 mg (vedolizumab) by infusion before starting maintenance treatment (see details in the SPC).»

Ulcerative colitis (UC):

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 ulcerative colitis in adults who have had an inadequate response with conventional therapy (aminosalicylates, corticosteroids and immunosuppressants), or in whom this treatment is contraindicated or poorly tolerated, TNFα antagonists (infliximab, adalimumab and golimumab) are the reference treatment. Vedolizumab (α4β7 integrin antagonist) may also be prescribed.

However, a TNFα antagonist 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, following the failure of conventional therapies and a TNFα antagonist, there are currently three alternatives: vedolizumab, tofacitinib (anti-JAK 1 and JAK 2) and ustekinumab. In the event of no response or loss of response to a TNFα antagonist, it is possible to increase the doses or the administration frequency of the TNFα antagonist or use another TNFα antagonist before considering treatment with vedolizumab or tofacitinib.

It should be noted that, according to the ANSM’s new guidelines issued in February 2020, XELJANZ (tofacitinib) should be used with caution in patients with known risk factors for thrombosis, regardless of the indication and dosage. Similarly, the use of tofacitinib at a dosage of 10 mg twice daily for the maintenance treatment of ulcerative colitis in patients with risk factors for thrombosis is not recommended, unless there is no alternative^[1].

Role of the medicinal product in the care pathway

The proprietary medicinal product ENTYVIO 108 mg (vedolizumab) administered subcutaneously is an alternative to the IV form of vedolizumab already available. Its role in the care pathway for the treatment of ulcerative colitis is identical to that of the IV form, as second or third-line treatment for patients with moderately to severely active ulcerative colitis with previous failure (inadequate response, loss of response, contraindication or intolerance) to conventional therapy or a TNFα antagonist.

However, a TNFα antagonist 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;
• infliximab being the recommended biologic therapy in the event of severe acute colitis (expert opinion).

[1] ANSM: Xeljanz (tofacitinib): new use guidelines in patients at high risk of thrombosis - Letter to healthcare professionals 06/02/2020