Source Article: Methotrexate Safety

A recent post (Monotherapy or Combination Therapy with Adalimumab) referenced an article indicating some potential concern for malignancy potential with methotrexate (Semin Arthritis Rheum 2014; 43: 489-97). Here’s a link to the source article/abstract:  Comparative cancer risk associated with methotrexate, other

The authors conducted a comparative effectiveness study with cancer as an outcome in patients with rheumatoid arthritis (RA).  The final sample size was 6806 patients.  The most common drugs examined included methotrexate (n=1566) and TNF antagonists (n=3761). Other disease-modifying anti-rheumatic drugs (DMARDs) included other non-biologics (n=904), rituximab (n=167), and abatacept (n=408).

The authors note that with “the advent of newer DMARDs and combination therapy (this) has allowed more RA patients to lead more functional lives.  With this improvement in therapy, more attention is focused on the comparative risks and benefits of treatment.”

Key findings/discussion:

  • TNF antagonists were associated “with a reduced overall cancer risk versus methotrexate.” (HR 0.29).  Figure 2B, shows a plot with specific HR for various malignancies.  TNF antagonists had a HR of 0.15 for lymphoma.
  • Oncogenic potential of methotrexate was described almost 20 years ago, however, “its obvious clinical benefits have overshadowed malignancy concerns.”
  • “Our findings suggest that when examining the cancer risk associated with other DMARDs, combined methotrexate use must be factor into adjusted analyses.”

How does this translate to inflammatory bowel disease (IBD)?  While RA and IBD patients may have different risks for malignancy, this study suggests that patients receiving methotrexate therapy may have a low risk of malignancy.  The potential benefits of methotrexate therapy along with alternatives need to be weighed against this possible risk. Perhaps, this article may help reduce the concerns regarding anti-TNF therapy with regard to relative risk.

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