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Structured evaluation of magnetic resonance imaging (MRI) is important to guide clinical decisions of perianal fistulas in Crohn's disease (CD) patients. To evaluate the recently developed modified Van Assche index to assess clinical responses to anti-tumor necrosis factor (TNF) therapy in patients with perianal fistulizing CD. A search of medical records identified patients with fistulizing perianal CD who underwent baseline and follow-up MRI while receiving anti-TNF treatment. Patients were divided into clinical responders and non-responders based on physician's assessment. MRI-scans were scored using the original and modified Van Assche index and scores between baseline and follow-up were compared within clinical responders and non-responders. Thirty cases were included (48% female, median age 27 years). Clinical responders (n = 16) had a median modified Van Assche score of 9.6 (IQR 5.8–12.7) at baseline and 5.8 (IQR 3.5–8.5) at follow-up (p = 0.008). In non-responders (n = 14), corresponding scores were 7.7 (IQR 5.8–13.5) and 8.2 (IQR 5.8–11.5) (p = 0.624). In clinical responders, 6/16 showed no drop in modified Van Assche score at follow-up. Scores obtained with the original Van Assche index dropped between baseline and follow-up in clinical responders (13.0 vs. 9.6, p = 0.011), whereas no decrease was observed in non-responders (11.5 vs. 11.5, p = 0.324). While the modified Van Assche index overall decreases significantly in patients with perianal fistulas responding to anti-TNF treatment, one third of responders had unaltered scores at follow-up. Also, outcomes were comparable to the original Van Assche index. Further optimization of the modified Van Assche index is needed before application in larger studies. • The modified Van Assche index decreases significantly in patients responding to anti-TNF therapy. • In one third of responders the modified Van Assche index did not drop between baseline and follow-up. • No clear added value of the modified over the original Van Assche index was found. • Further optimization of the modified Van Assche index should be realized. [ABSTRACT FROM AUTHOR]