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Researchers Examine Why Biologics Stop Working

By Melissa Leavitt

If you're using a biologic drug, such as Remicade (infliximab) or Humira (adalimumab), you may be asking yourself why your new treatment has suddenly stopped working.

Many people with psoriasis who take these drugs see an initial period of improvement, followed by a drop in the drug's effectiveness. To better understand—and ultimately prevent—this decline, researchers are taking a closer look at anti-drug antibodies (ADAs).

In "Antidrug Antibodies in Psoriasis: A Systematic Review," a recent article from British Journal of Dermatology, researchers examined previous studies of biologic drugs to determine how ADAs interfere with the ability of biologics to improve psoriasis. Some people with psoriasis develop ADAs in response to biologics, which can make these treatments less effective.

The researchers reviewed 25 studies of biologics, focusing on four specific medications: Remicade, Humira, Enbrel (etanercept) and Stelara (ustekinumab). Taken together, the studies examined almost 8,000 patients, 950 of whom tested positive for ADAs. Researchers identified a connection between ADAs and decreased patient response in studies of two drugs: Remicade and Humira. Studies of Enbrel did not reveal a connection between ADAs and patient response, while studies of Stelara were inconclusive.

In one study of Remicade, only 39 percent of patients who tested positive for ADAs maintained improvement through week 50 of their treatment. A study of Humira showed similar results, with 42 percent of patients who tested positive for ADAs no longer responding to treatment after one year.

Biologics, drugs that are derived from living cells, target specific parts of the immune system. They differ from systemic drugs, which affect the entire immune system. Remicade, Humira and Enbrel target tumor necrosis factor-alpha (TNF-alpha), which is a protein that tells the body to create inflammation. Stelara blocks a different class of proteins, interleukin-12 (IL-12) and interleukin-23 (IL-23), which are associated with inflammation in people with psoriasis.

The researchers also examined these same studies to determine whether taking methotrexate, a systemic medication, in conjunction with a biologic could reduce the formation of ADAs. Some patients find that taking the two medications together can help sustain the improvements they see from biologics. Researchers found that, although the two medications have not been extensively studied together, the available data does suggest that methotrexate can reduce the prevalence of ADAs.

The researchers suggest that future studies should continue to examine the role of ADAs in decreasing the effectiveness of biologic treatments, and the potential use of methotrexate to combat ADAs.

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