Methotrexate in patients with Crohn's disease after 6-mercaptopurine☆,☆☆,★,★★

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Abstract

Objective: The objective of this study was to describe the clinical outcome of children with Crohn's disease treated with subcutaneous methotrexate. Subjects/Methods: Fourteen patients (10 boys) with extensive Crohn's disease diagnosed at a mean age of 10.6 ± 3.6 years had previously received various medical therapies for 4.3 ± 4.0 years. Because of the severity of their disease, 6-mercaptopurine had been introduced but discontinued because of the patients' failure to respond (n = 11) or the development of pancreatitis (n = 3). Subsequently, low-dose, weekly, subcutaneous methotrexate was initiated. Pediatric Crohn's Disease Activity Index scores and prednisone requirement were followed as outcome measures. Results: Overall, 9 (64%) of the 14 patients showed improvement, including 6 (55%) of 11 patients who had previously received an adequate trial of 6-mercaptopurine and all three patients who were intolerant of 6-mercaptopurine. Improvement in clinical and laboratory measures occurred by 4 weeks and were similar whether (n = 8) or not (n = 6) the dose of corticosteroids was increased before the start of subcutaneous methotrexate. Three patients were tapered from their initial methotrexate dose after the minimization of corticosteroids and remain well. One patient receiving daily corticosteroids died suddenly after acute onset of illness. Among patients responding, methotrexate was discontinued because of side effects (n = 2) or electively (n = 2). Of the latter two patients, one has resumed methotrexate after disease relapse, whereas the other patient has had a sustained remission. Conclusions: Low-dose, weekly, subcutaneous methotrexate can induce remission in some pediatric patients with Crohn's disease who fail to adequately respond to other immunomodulator medications. (J Pediatr 1998;132:830-5)

Section snippets

Patients

The 14 patients (10 male) selected were those with active corticosteroid-dependent CD who failed to maintain remission while receiving 6MP or were intolerant of 6MP use. The mean age at the time of CD diagnosis was 10.6 ± 3.6 years (range 3.0 to 14.3 years); all were monitored at one institution, and most (n = 11) were monitored prospectively. The diagnosis was established by the usual clinical, radiologic, endoscopic, and histologic criteria. Sites of intestinal involvement were determined by

RESULTS

The mean age at introduction of MTX was 15.1 ± 3.1 years. The mean duration of therapy was 8.1 ± 5.4 months (range 1 to 16 months). The mean PCDAI score after 4 weeks of therapy (8 ± 7 points) was lower than at the start of subcutaneous therapy (31 ±12 points, p < 0.001). Serial PCDAI measurements initially improved in all patients (Fig. 2).

. Serial PCDAI score determinations after initiation of subcutaneous methotrexate (time 0). Score determined when patients were receiving (solid lines) and

DISCUSSION

This study shows that some patients with difficult to manage CD may gain benefit from the use of subcutaneous MTX. It could be expected that those patients with CD intolerant of 6MP would be likely to benefit from MTX, because 6MP and MTX both appear to exert their effects in a multifactorial manner involving both cellular and antiinflammatory actions.1, 19, 20 In addition, 6 of the 11 patients who had active CD despite 6MP therapy at generally accepted adequate doses and for adequate lengths

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    ☆

    From the Combined Section of Pediatric Gastroenterology and Nutrition, Departments of Pediatrics, University of Nebraska Medical Center, Creighton University, and Children's Hospital, Omaha, Nebraska.

    ☆☆

    Dr. Mack is supported by a grant from the National Institutes of Health (DK02205).

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    Reprint requests: David R. Mack, MD, University of Nebraska Medical Center, 600 South 42nd St., Omaha, NE 68198-5160.

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