Potential drug–drug interactions with JAK inhibitors may be going unrecognized
medwireNews: In an analysis of a large US claims database, around 10% of patients with rheumatoid arthritis (RA) were prescribed a drug with the potential to interact with Janus kinase (JAK) inhibitors.
“These results confirm that DDIs [drug–drug interactions] 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,” explain Alison Walton (Butler University, Indianapolis, Indiana, USA) and team.
They add that “[a]s treatment options and polypharmacy management expand, rheumatologists should consider potential DDIs and adjust treatment according to the respective drug-label recommendations.”
Walton and team used the IBM MarketScan Research Commercial and the Medicare Supplemental Database to evaluate the frequency of claims for drugs with the potential to interact with JAK inhibitors. Evaluable data were collected from 152,853 people with RA (76% women; median 57 years of age) who had at least two outpatient claims 30 or more days apart or at least one inpatient claim, between 2013 and 2017.
In total 1.62% of patients were prescribed tofacitinib – the only JAK inhibitor available during the study period – while 67.12% and 33.75% were prescribed conventional and biologic DMARDs, respectively.
The researchers report in Rheumatology and Therapy that the most common treatments with the potential to interact with JAK inhibitors were moderate cytochrome P450 (CYP)3A4 inhibitors and strong CYP2C19 inhibitors, at 22.21% and 15.66%, respectively. And the two treatments combined were claimed by 9.63% of patients.
A further 3.16% of patients had claims for strong CYP3A4 inhibitors alone (namely clarithromycin), 1.00% of patients had claims for strong CYP3A4 and CYP2C19 inhibitors combined, and 0.06% of patients had claims for strong organic anion transporter 3 inhibitors alone, most commonly probenecid.
The researchers acknowledge that “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,”
Walton et al therefore conclude that “[r]heumatologists should consider potential DDIs when managing patients with RA.,” and they add: “Many of the potentially interacting drugs observed in this real-world analysis may be used acutely (e.g., antifungals), which may require a temporary treatment interruption or dose adjustment of the chronic RA therapy.”
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