Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients With Active Luminal Crohn's Disease

Abstract

Background and aims: Vitamin D has a regulatory role in innate and adaptive immune processes. Previous studies have reported that low pretreatment vitamin D concentrations are associated with primary non-response (PNR) and non-remission to anti-TNF therapy. This study aimed to assess whether pretreatment 25-hydroxyvitamin D concentrations predicted PNR and non-remission to infliximab and adalimumab in patients with active luminal Crohn's disease.

Methods: 25-Hydroxyvitamin D concentrations were measured in stored baseline samples from 659 infliximab- and 448 adalimumab-treated patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study. Cut-offs for vitamin D were deficiency <25 nmol/L, insufficiency 25-50 nmol/L, and adequacy/sufficiency >50 nmol/L.

Results: About 17.1% (189/1107; 95% CI, 15.0-19.4) and 47.7% (528/1107; 95% CI, 44.8-50.6) of patients had vitamin D deficiency and insufficiency, respectively. 22.2% (246/1107) of patients were receiving vitamin D supplementation. Multivariable analysis confirmed that sampling during non-summer months, South Asian ethnicity, lower serum albumin concentrations, and non-treatment with vitamin D supplementation were independently associated with lower vitamin D concentrations. Pretreatment vitamin D status did not predict response or remission to anti-TNF therapy at week 14 (infliximab P_pnr = .89, adalimumab P_pnr = .18) or non-remission at week 54 (infliximab P = .13, adalimumab P = .58). Vitamin D deficiency was, however, associated with a longer time to immunogenicity in patients treated with infliximab, but not adalimumab.

Conclusions: Vitamin D deficiency is common in patients with active Crohn's disease. Unlike previous studies, pretreatment vitamin D concentration did not predict PNR to anti-TNF treatment at week 14 or nonremission at week 54.

Keywords: Crohn’s disease; IBD; PANTS; vitamin D.

Figure 1.

Study profile. Patients were not assessable when 1 or more of the key data items were missing.

Figure 2.

Forest plot showing the coefficients from a multivariable linear regression model of associations with pretreatment vitamin D concentrations. The resultant values represent the change in vitamin D concentrations associated with each variable. CRP, C-reactive protein; HBI, Harvey Bradshaw Index; sPCDAI, short pediatric Crohn’s disease activity index. ^†Sampling during the summer was defined as a blood sample obtained in the months of June, July, and August.

Figure 3:

Proportion of patients stratified by their pretreatment vitamin D status and outcomes to anti-TNF at (A) week 14 and (B) week 54. Infliximab-treated patients on the left panel, and adalimumab-treated patients on the right panel. The number of patients experiencing each outcome is annotated in the plot, with the proportion in brackets (%). PNR, primary non-response.

Figure 4.

Kaplan–Meier estimates of time to the development of anti-TNF antibodies in patients stratified by pretreatment vitamin D status. Infliximab-treated patients are shown in (A) and adalimumab-treated patients in (B). P-values calculated using the log-rank test. Shaded regions represent the 95% CI.

Figure 5.

Forest plot showing the hazard ratio of the factors associated with time to the development of anti-TNF antibodies in infliximab-treated patients. ^†Patients with either 1 or 2 copies of the allele were considered to have carriage of the HLA-DQA1*05 variant.