P362 Influence of HLA DQA1*05 genotype in patients with inflammatory bowel disease and Anti-TNF treatment with proactive therapeutic drug monitoring
Authors: Fuentes-Valenzuela E , García-Alonso F J , Maroto-Martín C , Juan-Casamayor L , Garrote Adrados J A , Almendros Muñoz R , de Prado Á , Marinero M Á , Calleja Carbajosa R , Vara Castrodeza A , Barrio J 
Published: January 2022

Background

The HLADQA1*05 variant increases the risk of developing antibodies against infliximab and adalimumab. Whether proactive therapeutic drug monitoring (PTDM) could overcome this immunogenicity remains unknown.

The primary aim was to evaluate the influence of the allele HLADQA1*05 on treatment persistence.

Methods

We performed a single centre retrospective cohort study. IBD patients starting anti-TNF therapy between January, 2017 and March, 2021 were included. HLA DQA1*05 genotype screening was performed during, 2021. PTDM was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, with according dose optimization. Patients not fulfilling these criteria were excluded. Target concentration during induction:, 25–30 mcg/ml (week, 2) and, 20 mcg/ml (week, 6) for Infliximab and &gt;, 10 mcg/ml (week, 2 and, 4) for Adalimumab. During maintenance:, 3–10 mcg/ml for Infliximab and, 8–12 mcg/ml for Adalimumab. Clinical remission was defined as HBI &lt;5 or pMS ≤, 2 without any item &gt;1 and biochemical remission as a fecal calprotectin&lt;250 mg/kg. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis.

Results

126 patients started anti-TNF therapy during the study period. Fourteen were excluded (8 lacked PTDM and, 6 declined the HLA DQA1*05 genotype), thus including, 112 patients with a median follow-up of, 73.9 (IQR:, 35.4–133.1) weeks, 52 (46.4%) HLADQA1*05 positive. Figure, 1 presents baseline characteristics. Combination therapy with thiopurines was more frequent among HLADQA1*05 negative patients (28 (46.7%) vs, 12 (23.1%), p=0.01).

During their first year, patients underwent a median of, 3 (IQR, 2–4) drug level measurements. We performed, 497 determinations (4/patient (IQR:3–6);, 149 (30%), drove to dose modifications, 63 (42.3%) among symptomatic patients and, 86 (57.7%) among asymptomatic ones.

Primary nonresponses were higher (8.1% vs, 0, p=0.06) among HLADQA1*05 negative patients. The HLADQA1*05 positive presented non-significant higher clinical remission rates at week, 14 (77.9% vs, 73.9%, p=0.69) and, 56 (73.2% vs, 68.4%, p=0.64) (figure 2).

Figures, 3 and, 4 presents drug persistence, which was higher among HLADQA1*05 positive patients (HR:, 0.32, 95% CI:, 0.14–0.71, p=0.01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (Hazard ratio (HR):, 4, 95% CI, 1.7–9.7) as a risk factor and a positive HLA DQA1*05 genotype (HR:0.31 (0.12–0.81)) as a protective factor of treatment cessation.

Fig.1

Fig. 2.

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Fig.4.

Conclusion: When PTDM is performed, a positive HLA DQA1*05 genotype does not associate a higher risk of treatment cessation.