Inflammatory bowel disease patients taking the biologicals Humira or Cimzia (certolizumab) are at significant risk of flare-ups if they delay refilling their prescriptions for more than two days out of two weeks, a study found.
The research, titled “Defining an Optimal Adherence Threshold for Patients Taking Subcutaneous Anti-TNFs for Inflammatory Bowel Diseases,” was published in the American Journal of Gastroenterology.
AbbVie’s Humira (adalimumab) and UCB’s Cimzia (certolizumab) inhibit tumor necrosis factor, a protein associated with bowel disease gut inflammation.
The two help more than half of IBD patients, but about a third fail to continue benefiting from them over time. One of the main reasons is that patients develop antibodies against them, blocking their actions or causing them to be cleared from the body.
Scientists believe intermittent use of the drugs — that is, taking them on and off — leads to the antibodies. Gaps in taking the treatments can cause flare-ups that require steroid use and hospitalizations.
Researchers wanted to determine the maximum time a patient could be off their therapy without experiencing a flare-up. They defined lower adherence to a therapy — that is, taking it less faithfully — as delays in filling prescriptions for it. Researchers used claims for steroids or hospitalizations as evidence that flare-ups had occurred.
The team identified 6,048 IBD patients whose claims appeared in the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. They included in their analysis only claims from patients’ latest treatment.
Researchers said 5,325 patients had been taking Humira and 723 Cimzia. Patients’ average age was 41, and 54 percent were women. Humira patients stuck to their treatment better than Cimzia patients.
The team calculated a medication possession ratio for each patient. It reflects the number of days a medication is supplied out of the number of days between refills. “For example, if a patient is dispensed a 28-day supply on 1 January and then another 28-day supply on 1 February,” the ratio is 56/59 or 0.95,” the authors wrote.
The minimum ratio for preventing the risk of a flare-up was 0.87 for Cimzia and 0.86 for Humira. This meant that missing more than four days of medication put the patient at high risk of a flare-up, the team said.
A ratio of “0.87 or higher is associated with a significantly lower risk of hospitalization or a new steroid prescription for those initiating certolizumab and an MPR [ratio] of 0.86 or higher for those starting adalimumab,” they wrote. “These adherence measures equate to missing only four days of medication in a 28-day cycle.”
The researchers noted that sometimes doses are missed for reasons that can’t be helped, such as when a patient has a bacterial infection or reacts to the injections.
“In conclusion, we have identified an association between adherence to subcutaneous biologics and hospitalizations and steroid use,” the team wrote. “We show that adherence levels should be maximized for these medications, ideally above an MPR of 0.87, to prevent poor outcomes. The adherence threshold of 0.87 allows for less than four days of missed medication per 28-day period.”
They added that future studies should be done “on the most effective interventions targeted to high-risk patients taking these medications who fall below this level of adherence.”