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The JAK inhibitor upadacitinib (Rinvoq) outperformed placebo in ankylosing spondylitis patients whose disease hadn't responded to standard biologic drug therapy, phase III trial data showed.

Almost half of patients receiving the oral medication (45%) met the study's primary endpoint, the so-called , compared with 18% of a placebo group in the randomized trial (P<0.0001), according to Désirée van der Heijde, MD, PhD, of Leiden University in the Netherlands, and colleagues.

Secondary efficacy endpoints also favored upadacitinib, the researchers , and safety findings were consistent with those seen in other trials.

These data, along with a similar trial among patients failing conventional nonbiologic agents, helped upadacitinib win this past April -- , following earlier OKs for rheumatoid and psoriatic arthritis, atopic dermatitis, and ulcerative colitis. In announcing the most recent approval, drugmaker AbbVie said it hopes to gain additional indications for upadacitinib such as Crohn's disease and giant cell arteritis.

Called , the newer trial enrolled 420 ankylosing spondylitis patients who had not achieved adequate symptom control with at least one inhibitor of tumor necrosis factor or interleukin-17. They were randomized to placebo or 15 mg of upadacitinib once daily for 14 weeks.

Three-quarters of patients enrolled in SELECT AXIS 2 were men, mean age 42 and disease duration of 13 years. Patients' self-scoring of overall disease activity at baseline averaged 7.3 on a 10-point scale.

The percentage of patients achieving ASAS40 -- 40% reduction in symptoms as defined by the Assessment of SpondyloArthritis International Society -- was chosen as the primary efficacy measure. The ASAS system brings together patients' self-ratings of overall disease severity, pain, stiffness, and functional ability. Other researchers have for drug therapy, as ASAS20 had been the primary endpoint in most previous trials.

By week 4, significantly more of the upadacitinib group had achieved ASAS40 relative to those assigned to placebo, and the gap continued to grow throughout the 14-week study period.

Other efficacy outcomes for upadacitinib versus placebo included the following (all P<0.0001):

• ASAS20: 65% vs 38%

• ASAS partial remission: 18% vs 4%

• Bath Ankylosing Spondylitis Disease Activity Index 50% reduction: 43% vs 17%

• Bath Ankylosing Spondylitis Functional Index change: -2.26 vs -1.09 points

Objective findings in MRI analyses also favored upadacitinib. As graded under the Spondyloarthritis Research Consortium of Canada system, changes from baseline with the active drug versus placebo were as follows:

• Spine: -3.95 vs -0.04 points

• Sacroiliac joint: -2.26 vs +1.05 points

With regard to safety, there was a hint that upadacitinib left participants more vulnerable to COVID-19. Six patients in the upadacitinib group experienced serious adverse events, of which four were COVID-19 infections, whereas only one placebo recipient had a serious event and it was tonsil cancer. Overall COVID-19 case counts were 12 with the active drug versus six in the placebo group.

That upadacitinib, like other JAK inhibitors, comes with a risk of infections was already known (their labels include a boxed warning about it), and indeed, five patients in the upadacitinib group had infections rated as serious (including the four related to COVID) versus none receiving placebo. On the other hand, three patients discontinued placebo because of adverse events compared with none assigned to upadacitinib.

Overall, van der Heijde and colleagues concluded, "[n]o new safety risks were identified compared with the known safety profile of upadacitinib."

A 90-week extension is currently underway.

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