Adding Methotrexate to anti-TNF therapy

While new therapies are emerging for inflammatory bowel disease as noted in recent blog entries on Vedolizumab and Tofacitinib, many patients have refractory disease and require management with available treatments.  One strategy in this situation has been to add methotrexate (Inflamm Bowel Dis 2012; 18: 1488-92).

This case series from the Mayo clinic reported their experience with 14 pediatric Crohn’s patients (10 males) who had methotrexate added to anti-TNF therapy.

Clinical remission was achieved in 50% (PCDAI <15) within 6 weeks with methotrexate (dose: 15 mg/meter squared –average dose 17.5mg SC weekly).  All patients received folate supplementation (1 mg daily). In this study, the average duration of methotrexate use was only 8.2 months & average followup was only 10 months.

Discussion notes that prior to methotrexate all patients had active disease despite anti-TNF therapy & most had received thiopurines. Most patients tolerated methotrexate. Four patients had Clostridium difficile infection; two cases were de novo.  Even after treatment of the infection, patients with Clostridium difficile were refractory to methotrexate treatment.

Of the initial 14 patients, two patients had severe nausea; this resulted in medication discontinuation in one patient and dose reduction in another patient.  No liver or kidney toxicity was identified.

Patients who did not respond to methotrexate, subsequent care including the following: three had surgery, one received tacrolimus/corticosteroids, one received natalizumab, one received certolizumab, and one received adalimumab/corticosteroids (while awaiting screening for certolizumab).

A prospective study of methotrexate is needed to confirm the its effectiveness in refractory Crohn’s and to determine long-term safety and efficacy.

Patient information on methotrexate (from my office website):  Methotrexate

Related blog entries:

Drug levels for inflammatory bowel disease

Methotrexate and liver toxicity

Additional methotrexate references:

-IBD 2011; 17: 2521. Methotrexate therapy: ~25% remission at 1yr, 16% at 2yrs.. n=93.
-JPGN 2011;53: 389. n=64. Supports use of zofran for 1st few months to prevent nausea.
-JPGN 2010; 51: 714. Use of MTX after thiopurines. n=27. 48% in remission at 6 months.
-JPGN 2009; 48: 526. Use in pediatric CD, n=25. 64% response

7 thoughts on “Adding Methotrexate to anti-TNF therapy

  1. There are five anti-TNF drugs that have been approved by the U.S. Food and Drug Administration to treat moderate to severe RA that has not responded to one or more of the traditional disease-modifying anti-rheumatic drugs. To decrease side effects and costs, most patients with mild or moderate disease are treated with methotrexate before adding or switching to an anti-TNF agent.

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