Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial.
Gut
; 69(7): 1206-1212, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-31980448
ABSTRACT
OBJECTIVES:
In patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period.DESIGN:
Consecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn's disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level >250 µg/g stool and for UC as a Mayo score >5 with endoscopic subscore >1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay).RESULTS:
Ninety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p<0.001; median time of clinical failure since randomisation 18 vs >24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p<0.001 for both) in monotherapy versus combination therapy. Only the use of combination therapy was associated with favourable outcomes after anti-TNF switch.CONCLUSION:
In case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF. TRIAL REGISTRATION NUMBER 03580876.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azatioprina
/
Doenças Inflamatórias Intestinais
/
Fator de Necrose Tumoral alfa
/
Imunossupressores
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Gut
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França