A post-hoc analysis of SELECT-COMPARE trial data makes a pretty clear suggestion of which treatment to pick for RA patients.
New research suggests upadacitinib is more efficacious than adalimumab in rheumatoid arthritis, even when considering cardiovascular risk factors.
Upadacitinib has previously been shown to be superior to adalimumab in the treatment of rheumatoid arthritis, although data on the long-term safety and efficacy of these drugs in patients with an increased risk of cardiovascular disease is lacking.
But recent research suggests that upadacitinib is more effective at treating RA symptoms regardless of a patient’s baseline CV disease risk.
“The findings of this study provide insights into the benefit-risk profiles of upadacitinib and adalimumab in patients with varying CV risks, suggesting that upadacitinib may offer efficacy advantages over adalimumab irrespective of baseline CV risk, with generally similar rates of adverse events,” the researchers wrote in RMD Open.
As part of the post-hoc analysis, researchers analysed up to five years of safety and efficacy data for roughly 1000 rheumatoid arthritis patients aged ≥ 18 years who had previously participated in the SELECT-COMPARE phase three trial.
Patients were categorised on their perceived cardiovascular disease risk as either low risk (people under the age of 65 and having no known CV risk factors) or high risk (people ≥ 65 years and/or with ≥ 1 CV risk factor). Examples of CV risk factors of interest included a prior history of a CV event, hypertension, diabetes, smoking status and an elevated LDL-cholesterol level.
There were 211 patients in the lower CV risk group (129 who received upadacitinib, 82 who received adalimumab) and 767 in the higher CV risk group (522 received upadacitinib, 245 received adalimumab). The demographic and baseline disease characteristics were similar between the two treatment groups within the lower and higher CV risk groups, while patients in the higher CV risk group were an average of 13 years older than their counterparts in the lower-risk group.
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The rates of adverse events (serious, treatment-related or other, including infections, malignancies, major CV events and venous thromboembolisms) were similar between the two treatment groups regardless of CV risk status, although patients in the higher CV risk group had an increased rate of adverse events compared to patients in the lower CV risk group.
The one difference between upadacitinib and adalimumab was a higher rate of herpes zoster infection for patients receiving upadacitinib compared to adalimumab after both six months and five years.
The researchers felt the safety findings were consistent with previous analyses of upadacitinib in RA and other approved indications.
Although the two drugs displayed similar safety profiles, patients who received upadacitinib performed better on all examined efficacy endpoints (including, but not limited to, a 28-joint Disease Activity Score based on C-reactive protein < 2.6, a Clinical Disease Activity Index score ≤ 2.8, a Simplified Disease Activity Index score ≤ 3.3 and changed in self-reported pain from baseline) in both the short- and long-term compared to patients who received adalimumab – with the benefits seeming to be more apparent in the lower risk group compared to the higher risk group.
“The reasons for this observation are unclear but underscore the importance of early intervention in the treatment paradigm,” the researchers wrote.
“Recent studies have suggested that JAK inhibitors may also have potential cardioprotective effects due to their ability to reduce inflammation and modulate cardiotoxic factors, although the underlying mechanism is not fully understood.
“The positive benefit–risk profile of upadacitinib, combined with the low number of events of special interest, supports the earlier use of JAK inhibitors. As always, these decisions should be made in conversation with the patient, considering their individual risk factors.”
