Safety and Efficacy of JAK Inhibitors for Treatment of RA

Results of a real-world study published in The Journal of Rheumatology validated the safety and effecacy of oral Janus kinase (JAK) inhibitors for the treatment of rheumatoid arthritis (RA), particularly among patients without pre-existing cardiovascular risk factors.

Researchers conducted a retrospective cohort study including patients with RA who were treated with any JAK inhibitor (tofacitinib, baricitinib, upadactinib, or filgotinib) at 4 care centers in Milan, Italy, and reported on their safety and efficacy.

Recorded outcomes for JAK inhibitor safety included major cardiovascular events and adverse events of special interest (AESI), such as serious infections, opportunistic infections, venous thromboembolism, herpes zoster infections, liver injury, malignancies, and death.

Cardiovascular risk was defined as patients aged over 50 years with at least 1 further risk factor in addition to current smoking, hypertension, low levels of high-density lipoprotein cholesterol (<40 mg/dL), diabetes, family history of premature coronary heart disease, extra-articular RA, or history of coronary artery disease.

A total of 685 patients (92% women; median age, 49 years) were included in the final analysis and received first-line treatment with JAK inhibitors prior to a biologic. Baricitinib was administered to 48% of patients, while 31% received tofacitinib, 14% were given upadacitinib, and 7% received filgotinib.

Patients received treatment with tofacitinib 5 mg twice daily, upadacitinib 15 mg once daily, and filgotinib 200 mg once daily. Among patients treated with baricitinib, 307 (92%) received 4 mg daily, while 26 (8%) received 2 mg daily.

Hypertension (32%), diabetes (7%), coronary artery disease (6.5%), and a history of venous thromboembolism (1.1%) were the most common comorbidities. Arterial hypertension and coronary artery disease were more prevalent among the tofacitinib group.

At 6 months, patients treated with tofacitinib had a retention rate of 92%, while those treated with baricitinib, upadacitinib, and filgotinib had treatment retention rates of 93%, 95%, and 96%, respectively. Retention rates for tofacitinib, baricitinib, upadacitinib, and filgotinib at final follow-up were 66%, 75%, 89%, and 93%, respectively.

Of the patients initially treated with JAK inhibitors, 169 had to change their treatment during follow-up due to adverse events or lack of efficacy. In total, 122 patients switched to biologic disease-modifying antirheumatic drugs, while 47 patients switched to a different JAK inhibitor.

A total of 123 AESIs were reported throughout the study. During the 1137 patient-years of observation, 3 deaths occurred, including 1 patient treated with tofacitinib and 2 treated with baricitinib. All 3 patient deaths were attributed to severe infections.

Regarding cardiovascular outcomes, 1 ischemic stroke event in the baricitinib treatment group was recorded.

Patients treated with upadacitinib and filgotinib had lower frequencies of adverse events compared with the other groups, while similar rates of AESIs were observed across all 4 groups when accounting for length of follow-up.

Among the 388 patients with cardiovascular risks, 23% experienced 1 AESI, compared with 18.5% of the general cohort.

This study was limited by its retrospective nature, variation in follow-up length among treatment groups, and overall short follow-up period.

The study authors concluded, “[C]linicians should envisage a cost-benefit approach, liberally employing [JAK inhibitors] in a priori comorbidities-free population while pondering their use in older patients with several [cardiovascular] risk factors and balancing the significant efficacy of this class of drugs with their potential safety issues.”