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JAK Inhibitors and Drug-Drug Interactions: Managing Medications for Rheumatoid Arthritis

April 23, 2021
When treating patients with rheumatoid arthritis and comorbid chronic conditions – signaling polypharmacy, close medication management is crucial.

with Kevin Byram, MD

Polypharmacy poses difficulties for clinicians in any area of medicine, but the challenge is particularly common when treating illnesses such as rheumatoid arthritis (RA). This chronic condition is associated with a high level of comorbidities, including hypertension, diabetes, osteoporosis, and dyslipidemia,1 and therefore involves a high rate of polypharmacy.

“It’s not uncommon for patients with RA to be on multiple medications for their RA, in addition to the medications for their other medical issues,” explains Kevin Byram, MD, assistant professor of medicine in the Division of Rheumatology and Immunology at the Vanderbilt University Medical Center.

In fact, one study found that 31% of people with rheumatoid arthritis below 65 years of age were on six or more medications, as were 52% of those over age 65. Sixteen percent of the over-65 group were on 10 or more medications.2 This type of medication regimen creates no small risk of drug-drug interactions (DDIs), which can, at the least, reduce the effectiveness of the medications and, at worst, increase the risk of poor outcomes and even death.2


One study found that 31% of people with rheumatoid arthritis below 65 years of age were on six or more medications. (iStock)

Recent advances in treatments for rheumatoid arthritis include Janus kinase (JAK) inhibitors, a type of disease-modifying anti-rheumatic drug (DMARD) that shows great promise for treating RA as well as other inflammatory diseases. However, there has been little research into potential interactions between these new drugs and others commonly taken by people with RA. Research published in January 2021 in Rheumatology and Therapy took a close look at the frequency of prescription claims for drugs that may interact with JAK inhibitors to see how much of a problem this poses for patients.

JAK Inhibitors for Rheumatoid Arthritis and Drug-Drug Interactions

A team of researchers, including four who are employees of Eli Lilly and Company (which manufactures the JAK inhibitor baricitinib), conducted an observational, retrospective, cross-sectional study. Researchers looked at data from the Medicare Supplemental database and the IBM MarketScan Research databases, capturing health data from approximately 100 payers and over 4.6 billion claims records. Data selected were limited to adults 18 years old or older with two or more outpatient claims 30 or more days apart or more than one inpatient visit claim with an RA diagnosis (using either ICD-9  or ICD-10 criteria) between January 1, 2013, and March 31, 2018. In addition, to be eligible, patients had to have at least 12 months of continuous medical and prescription coverage with no more than a 29-day gap in coverage.

A total of 152,853 patients met the eligibility requirements. Of these approximately 75% were women, 60% were between 45- and 64-years-old, and the median age of participants was 57 years. Drugs that were considered to have the potential for DDIs with JAK inhibitors were:

  • strong organic anion transporter (OAT3) inhibitors
  • strong cytochrome P450 (CYP) 3A4 inhibitors
  • moderate or strong CYP3A4 inhibitors in combination with strong CYP2C19 inhibitors.

Commonly prescribed drugs such as lovastatin and fluoxetine were included as a result.

The researchers found that up to 10% of the patients in the cohort were prescribed a drug that had the potential to interfere with JAK inhibitors. “These results,” the study’s authors wrote, “confirm that DDIs are a risk for RA patients and, subsequently, there is a need to recognize and manage DDIs to minimize the risk of therapeutic failure or of adverse drug effects.”3

The researchers also acknowledged that medication management can be difficult when a patient has multiple physicians, adding, “drugs identified with potential DDI are often prescribed by primary care providers; whereas DMARDs, such as JAK inhibitors, are more likely prescribed by rheumatologists. Thus, DDIs may be missed at the point of prescribing.”

Use PDMPs and Pharmacists to Avoid Potential Drug-Drug-Interactions

After prescribing, the challenge for clinicians is two-fold. First, they must rely on patients’ reporting and memories of which medications they are taking to manage their RA and comorbid conditions (PDMPs provide a crucial assist), and, second, they must keep up with a patients’ changing prescription regimen and medication adherence. “Performing a good medication reconciliation can be helpful in this,” said Dr. Byram. “Being aware of potential interactions or medications with a lot of interactions is key as well.”

In addition to clinical PDMP use, Dr. Byram said he encourages his patients to use the same pharmacy for all medications, if possible. “This way, the pharmacist there can assist in finding medication interactions,” he says. “Prescribing with e-Prescribe through the medical record can also be helpful, as most systems will perform some sort of medication interaction analysis. I do not rely on this exclusively, but it is a good safeguard.”

Last updated on: April 23, 2021
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