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.
Conclusions: 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.