Physician Panel Explores Dose Reduction in Biologic Therapies

Last week, the American College of Rheumatology (ACR) held its Winter Rheumatology Symposium in Snowmass, Colorado. One of the sessions comprised a panel addressing treatment options for inflammatory arthritis. The following doctors made up the panel: Joel M. Kremer, MD, Center for Rheumatology, LLP; Vivian Bykerk, MD, FRCPC, Hospital for Special Surgery; Eric L. Matteson, MD, Mayo Clinic; Christopher T. Ritchlin, MD, MPH, University of Rochester; and Michael E. Weinblatt, MD, Brigham and Women’s Hospital (moderator).

During the session, the panel members were given case studies, 1 of which involved the pros and cons of dose reduction versus an increase in dosing interval of a biologic for a patient with rheumatoid arthritis (RA) who has achieved low disease activity or remission.

Weinblatt asked his fellow panelists, “Do you lower the dose or stretch out the interval of a biologic in someone in low disease activity or remission? Is it better to reduce the dose, or to increase the dosing interval?”

The approach was the same among the panelists, including the moderator; rheumatologists would increase the dosing interval, rather than reduce the dose.

Matteson said that his rationale for adjusting the time interval instead of the dose was that patients are usually on fixed dosages, and “the syringe only has a certain amount of the drug in it.”

Kremer, Bykerk, and Ritchlin all stressed the fact that the patient’s adherence should also be evaluated before making a change in treatment. “Often, patients adjust their own medications and dosing intervals, so before making a change like this, the prescriber should be clear on what the patient is taking and how often they’re taking it,” said Bykerk.

Weinblatt closed out the question by offering his own view, emphasizing that if an adjustment is made to the treatment regimen, methotrexate should still be included.

“I personally think that if [the patient] is antibody-positive, you can’t expect the drug to do everything if you’re stretching out the interval. You [also] need methotrexate. We know based upon some well-done studies with adalimumab that they need to be on at least 10 mg a week of methotrexate if you’re stretching out the adalimumab intervals to maintain clinical response and reduce the risk of antibodies,” said Weinblatt.

Overall, the panel agreed that, in patients in low disease activity or remission, they would each look to adjust the treatment regimen. In each of their practices, panelists suggested that they have had some success with this course of action already, but did note that the long-term (5 years and beyond) effect caused by stretching out the dosage intervals is currently unknown.

The panelists’ points of view appear to be in line with broader thinking on handling biologics in patients who have achieved low disease activity or even remission; treatment is becoming increasingly expensive for patients with inflammatory diseases. Given the length of time that patients typically receive treatment, the cost to the patient—and the payer—is mounting. In an effort to address these rising costs as well as limit the amount of drugs patients are taking, some studies have sought to examine the feasibility of dose reduction. Researchers involved in such studies aim to investigate whether decreasing the dose, or increasing the time interval between doses, could lead to some cost-savings while maintaining efficacy.