P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?
Carbery, I.(1)*;Lin, S.(2);Chanchlani, N.(2);Janjua, M.(2);Nice, R.(3);McDonald, T.J.(3);Bewshea, C.(4);Kennedy, N.A.(2);Ahmad, T.(2);Goodhand, J.R.(2);Selinger, C.P.(1);
(1)Leeds Teaching Hospitals NHS Trust, Leeds Gastroenterology Institute, Leeds, United Kingdom;(2)University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, United Kingdom;(3)Royal Devon and Exeter NHS Foundation Trust, Biochemistry- Exeter Clinical Laboratory International, Exeter, United Kingdom;(4)Royal Devon and Exeter NHS Foundation Trust, Gastroenterology, Exeter, United Kingdom;
Background
Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with IBD. We sought to assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn’s disease.
Methods
We included 997 adult participants from the Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS). Thyroid function tests, using the Roche Elecsys TSH immunoassay and T3 and T4 electrochemiluminescence assays, were measured on stored baseline samples (prior to biologic treatment). PNR, assessed at week 14, was defined as treatment failure (including IBD-related surgery), ongoing corticosteroid use, or both CRP failing to fall to ≤3 mg/L, or by 50% from baseline, and HBI failing to fall to ≤4, or by 3 points. Non-remission, assessed at week 54, was defined as either CRP of > 3mg/L or HBI of >4 points, ongoing corticosteroid therapy, or exit for treatment failure.
Results
Serum fT3, fT4 and TSH concentrations were similar in infliximab (n=549) and adalimumab treated (n=448) patients. Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27 - 0.34] vs 0.32 [0.28 - 0.36], p<0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25 - 0.33] vs 0.32 [0.29 - 0.36], p<0.001).
Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (OR 0.51, 95% CI 0.31 – 0.85, p = 0.009), however when stratified by drug and adjusted for variables known to be associated with PNR, low fT3/fT4 ratio remained associated with PNR for adalimumab, but not infliximab. After excluding patients treated with corticosteroids at baseline, there was no difference in fT3/fT4 ratio in those who experienced PNR compared to those who did not (PNR: [128/630] 0.31 [0.28 – 0.35] vs no PNR: [502/630] 0.32 [0.29 – 0.36], p = 0.095). The optimal threshold to determine PNR was 0.31 (AUC 0.57 [95% CI 0.54 - 0.61] sensitivity 0.62 [95% CI 0.41 - 0.74], specificity 0.53 [95% CI 0.42 - 0.73]).
No association was seen for baseline fT3/fT4 ratio and non-remission or changes in faecal calprotectin concentrations at week 54.
Conclusion
Lower baseline serum fT3/fT4 ratio was independently associated with female sex, higher inflammatory burden at baseline, and baseline corticosteroid use, and predicted PNR to anti-TNF therapy at week 14, but not non-remission or change in faecal calprotectin concentrations at week 54. Overall, however, the diagnostic accuracy of baseline fT3/fT4 ratio to predict PNR to anti-TNF treatment was modest, limiting its clinical utility.