Switching Antirheumatic Therapies Has Low Risk of Clinical Worsening

September 13, 2020

In the MONARCH OLE study, more than 50% of patients with rheumatoid arthritis who had low or inadequate response to adalimumab and switched to sarilumab experienced an improvement in disease activity.

There is a very low risk of rheumatoid arthritis worsening as a result of changing treatments due to partial or inadequate response, a new study finds. In fact, more than half of such patients treated with adalimumab who had switched to sarilumab experienced clinically meaningful improvements.

These findings were presented at the Clinical Congress of Rheumatology (CCR) East 2020 meeting.

Current guidelines recommend making any necessary therapeutic adjustments if rheumatoid arthritis patients fail to meet treatment goals or remission. Although patients may express health concerns over switching, there have been no data that assesses the association between therapy switching and disease exacerbation.

To fill this gap, a team led by Jeffrey Curtis, MD, MS, MPH, Professor of Medicine at the University of Alabama at Birmingham, performed a post-hoc analysis of the MONARCH Open-Label Extension (OLE) study and evaluated the effects of switching from adalimumab to sarilumab in patients who had partial response to treatment.

Patients who had been randomized to receive 40 mg of adalimumab during the double-blind phase were then transferred to receive 200 mg of sarilumab at the start of the extension study. Those initially receiving sarilumab continued with the regiment during open-label.

The extension study had enrolled a total 320 patients, and 155 ended up switching to the sarilumab group, with 165 maintaining sarilumab treatment.

At OLE baseline, 52% of the population had experienced partial response during the double-blind phase. The investigators noted that, as expected, partial responders were more prominent in the switch group (59%)—versus the continuation group (45%).

Furthermore, the continuation group partial responders had similar but numerically lower disease activity scores at OLE baseline—with the exception of tender joint count (TJC) and swollen joint count (SJC).

For the post-hoc analysis, Curtis and team defined partial response as patients with continued moderate-to-high disease activity (Clinical Disease Activity Index [CDAI] > 10) at OLE baseline, regardless of if minimal clinically important difference (MCID) and CDAI had improved following the double-blind phase.

The MCID threshold for patients with high-disease activity at double-blind phase baseline (CDAI<22) was 12 units. The threshold for those with moderate disease activity was 6 units.

After week 24, they noted that only a few partial responders in the switch (6%) and continuation (4%) experienced a worsening of disease activity.

On the contrary, up to 57% of patients in the switch group and 43% in the continuation group experienced improvements in disease activity.

There was no observed change of disease activity in 37% and 53% of the switch and continuation cohorts, respectively.

And finally, the team reported that between OLE baseline and week 24, the mean changes in efficacy parameters and patient reported outcomes had numerically increased. The only exception was SJC28.

“A small risk of worsening with the substantial likelihood of meaningful improvement may help alleviate patient fears of worsening when considering a switch to an alternative therapy, such as sarilumab,” they concluded.

The study, “Low Probability of Clinical Worsening Following Switching Biologic Disease-Modifying Antirheumatic Drug in Patients with Rheumatoid Arthritis and Partial Response to Adalimumab,” was presented at CCR East.