Upadacitinib reduces psoriatic arthritis, ankylosing spondylitis pain through 1 year
Patients with psoriatic arthritis or ankylosing spondylitis who received once daily upadacitinib 15 mg experienced improvements in pain measures through 1 year, according to data published in RMD Open.
“The primary goal in treating patients with PsA and AS is to maximize health-related quality of life by controlling symptoms and inflammation, preventing structural damage and normalizing function and social participation,” Iain B. McInnes, MD, of the University of Glasgow, and co-authors wrote. “A recommended treatment target is achieving remission or low disease activity through regular disease activity assessments and appropriate therapy adjustment.
“However, this treatment target is not always associated with corresponding improvement in patient-reported outcomes, such as pain and functional impairment,” they added. “... Currently available analgesics are poorly suited for chronic administration in patients with spondyloarthritis, and novel approaches to manage this important element of the disease are required.”
To evaluate the effects of upadacitinib (Rinvoq, AbbVie) 15 mg in patients with PsA or AS, McInnes and colleagues reviewed data from the SELECT-PsA 1 and SELECT-PsA 2 studies, as well as the SELECT-AXIS 1 study. In the SELECT-PsA 2 and SELECT-AXIS 1 studies, patients were randomized to receive upadacitinib 15 mg daily or placebo, while patients in the SELECT-PsA 1 trial received upadacitinib 15 mg daily, adalimumab (Humira, AbbVie) 40 mg every other week or placebo.
In all three trials, improvements in pain were assessed post hoc as the proportions of patients experiencing 30%, 50% or 70% reduction from baseline in global assessment of pain, as well as back, neck and hip pain.
In SELECT-PsA, a total of 429 participants were randomized to receive upadacitinib, 429 received adalimumab and 211 began with placebo before ultimately switching to upadacitinib. Among these participants, 352, 353 and 172, respectively, completed 56 weeks of treatment. For SELECT-PsA 2, a total of 211 patients were randomized to upadacitinib and 106 received placebo prior to switching, with 167 and 69, respectively, completing 56 weeks.
Lastly, a total of 93 patients with AS were randomized in SELECT-AXIS 1 to receive upadacitinib while 94 received placebo prior to switching. Among these, 78 and 82 participants, respectively completed 64 weeks of treatment.
According to the researchers, significantly more patients in the PsA studies who received upadacitinib 15 mg demonstrated “clinically meaningful” improvement in pain assessment with up to 30%, 50% and 70% reductions in pain as early as 2 weeks, which were sustained through the year. In addition, median time to improvement was significantly shorter in patients receiving upadacitinib 15 mg vs. patients receiving placebo.
In the AS study, a higher proportion of patients receiving upadacitinib 15 mg achieved meaningful improvement vs. placebo, including 30% and 50% reductions in pain; a 70% reduction in pain was observed at 4 weeks, which was sustained.
Further, patients who received placebo for 14 weeks before switching to upadacitinib 15 mg daily saw similar improvement as patients randomized to upadacitinib from the beginning.
“This analysis of data from three randomized placebo-controlled clinical trials from patients with active PsA or AS demonstrated consistent, rapid, clinically meaningful and sustained benefits on various pain end points (including global pain, peripheral/entheseal pain, back pain and nocturnal back pain) with upadacitinib 15 mg once daily,” McInnes and colleagues wrote. “Reductions were often achieved as early as week 2, and the reductions in pain were sustained over 1 year.”
Perspective
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Upadacitinib is the third JAK inhibitor to show pain relief in inflammatory rheumatic musculoskeletal disease. This article is a post hoc analysis, as was a previous tofacitinib article — demonstrating pain relief in patients with inflammatory rheumatic musculoskeletal diseases — from Ogdie et al.
Post hoc analyses are fraught with danger as has been documented elsewhere. To quote Dr. John Fletcher in his 2007 article in the BMJ: “This approach to analysis is similar to the sharpshooter who fires at a barn and then paints a target around the bullet hole. A target shows how accurate the shot was only if it was in place before the shooting.”
Pain relief was seen as early as week 2 in this inquiry. There was sustained pain relief up to 1 year. The authors acknowledge that the subjects were not randomized for pain, and that SELECT-AXIS 1 was a small study. They also acknowledge that BASDAI questions were used to assess pain, and the individual questions have not been validated for individual use, and therefore were “exploratory.”
On the positive side, baseline pain levels were generally balanced across the treatment arms, patients were blinded to treatment at baseline, the PsA group was large, and the results were consistent across PsA and AS.
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