Ustekinumab as alternative for anti-TNFs in HLA-DQA1*05-positive Crohn’s disease

In a cohort of the ENEIDA registry, carriage of the HLA-DQA1*05 allele did not influence ustekinumab treatment outcomes in patients with Crohn’s disease (CD). Therefore, the agent may be considered as an alternative to TNF inhibitors in patients with CD carrying this allele, in whom it is known that the efficacy of TNF inhibitors is compromised.

“Carriage of the HLA-DQA1*05 allele is associated with the development of anti-drug antibodies to TNF inhibitors in patients with CD, hampering the efficacy of these drugs,” explained Dr Jordi Guardiola (University Hospital Bellvitge, Spain) [1–3]. “Proactive anti-TNF therapy optimisation or combining anti-TNFs with an immunomodulator are options to overcome this issue but are not feasible solutions in all patients” [4]. Therefore, Dr Guardiola and co-investigators evaluated the influence of HLA-DQA1*05 carriage on the IL-12/23 blocker ustekinumab treatment outcomes in patients with active CD through a multicentre, retrospective, cohort study (n=204; HLA-DQA1*05 carriage n=85) [1].

There was no association between carriage of the HLA-DQA1*05 allele and time to loss of response to ustekinumab therapy (HR 0.99; 95% CI 0.6–1.7; P=0.99). “This result was consistent, irrespective of concomitant use of an immunomodulator or the number of previous biologicals that had been administered,” added Dr Guardiola. Similarly, the persistence of ustekinumab treatment was comparable for HLA-DQA1*05 carriers and non-carriers (HR 0.92; 95% CI 0.5–1.8; P=0.81). Finally, clinical and biological remission rates at week 26 and week 52 were identical for both patient groups.

“First-line treatment with ustekinumab rather than TNF inhibitors may be considered in HLA-DQA1*05-positive patients with CD, particularly when the use of a concomitant immunosuppressant is contraindicated and proactive therapeutic drug monitoring is not feasible,” decided Dr Guardiola.

1. Guardiola J, et al. Effect of the HLA-DQA1*05 allele on the efficacy of Ustekinumab in patients with Crohn’s Disease. Multicenter study based on the ENEIDA registry of GETECCU. OP37, 19^th Congress of ECCO, 21–24 February 2024, Stockholm, Sweden.
2. Sazonovs A, et al. Gastroenterology. 2020;158:189-199.
3. Solitano V, et al. Clin Gastroenterol Hepatol. 2023;21(12):3019-3029.
4. Bergstein S, et al. J Crohn’s and Colitis. 2023;17; Issue Supplement_1:i148-i150.

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Posted on 18 April 202418 April 2024