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P322 A change in ΔMCV predicts mucosal healing in patients with Crohn's disease under combination therapy

Bernardo S., Fernandes S., Correia L., Velosa J.

Hospital Santa Maria, CHLN, Department of Gastroenterology and Hepatology, Lisbon, Portugal

Background

Higher tioguanine (6-TGN) levels have been associated with better clinical and endoscopic outcomes in patients with inflammatory bowel disease under thiopurine therapy. Unfortunately dosing of 6-TGN levels is not available in most centers. Previous studies have suggested that an elevated erythrocyte mean corpuscular volume (MCV) can be a valid surrogate of adequate 6-TGN levels.

Methods

This was a retrospective study using a cohort of patients under combination therapy with Infliximab and azathioprine followed in a single center. We evaluated the influence of a ΔMCV in major endpoints including clinical and endoscopic response and remission at the end of the first year of treatment. Clinical response was defined as a decrease of 3 points in Harvey-Bradshaw Index and clinical remission as a Harvey-Bradshaw Index ≤4. Endoscopic response was defined as improvement in endoscopic appearance and endoscopic remission as the absent of ulcers. In a subgroup of patients anti-TNF pharmacokinetics (serum levels and antibodies) were also evaluated.

Results

143 patients with Crohn's Disease (CD) were included, 76 patients (53.1%) male with mean age of 28±11.5 years. MCV at baseline and at week 48 of treatment was 88.2fL±15.8 and 89.7fL±4.7. At the end of the first year of combination therapy, 87.4% patients achieved clinical response, 74.1% clinical remission, 83.9% endoscopic response and 43.4% endoscopic remission.

Patients with higher variations in MCV were more likely to be in clinical remission (3.16±4.94 vs −0.95±6.44, p<0.001). There was no statistical significance between ΔMCV and clinical response. Patients with endoscopic response and remission had higher ΔMCV (2.57±3.70 vs −3.38±7.05, p<0.001 and 3.17±3.97 vs −0.27±5.74, p=0.006).

The area under the receiver-operating curve (auroc) for predicting endoscopic remission, endoscopic response and clinical remission according to the ΔMCV was 0.665 (95% CI 0.532–0.797, p=0.025), 0.714 (95% CI 0.545–0.883, p=0.011) and 0.711 (95% CI 0.616–0.806, p<0.001).

For each unit increase in MCV level there was a significant increase in the probability of achieving clinical remission- OR 1.17 (95% CI 1.07–1.27, p=0.001), endoscopic response- OR 1.29 (95% CI 1.10–1.50, p=0.001) and endoscopic remission- OR 1.17 (95% CI 1.027–1.326, p=0.018). There was a negative correlation between C-reactive protein (CRP) levels and ΔMCV (Spearman's ρ=−0.254, p=0.003); patients with a negative CRP at week 48 had higher ΔMCV (5.67±5.37 vs 3.45±4.71, p=0.012). We found no significant association between ΔMCV and Infliximab through levels and antibodies.

Conclusion

Our results suggest an association between ΔMCV and better outcomes in CD patients under combination therapy. Assessment of ΔMCV may be an alternative to 6-TGN dosing.