Upadacitinib 15 and 30 mg significantly improves symptoms for patients with rheumatoid arthritis (RA) with an inadequate response to biologic disease-modifying anti-rheumatic drugs (bDMARDs) or conventional synthetic DMARDs (csDMARDs), according to results of 2 studies published in The Lancet.

In the SELECT-BEYOND study,1 the phase 3 trial (ClinicalTrials.gov identifier: NCT02706847) included participants who were aged 18 years or older with active RA and previous inadequate response or intolerance to bDMARDs and who were receiving concomitant background csDMARDs (n=499). Participants were assigned to receive once-daily oral extended-release upadacitinib 15 mg (n=165), 30 mg (n=165), or placebo (n=85) for 12 weeks, followed by upadacitinib 15 or 30 mg thereafter. The primary end points were the proportion of participants who achieved a 20% improvement in American College of Rheumatology criteria (ACR20) at 12 weeks and the proportion of participants who achieved a 28-joint disease activity score using C-reactive protein (DAS28-CRP) of 3.2 or less at 12 weeks.

At 12 weeks, 65% (n=106) of participants in the upadacitinib 15-mg group and 56% (n=93) of participants in the 30-mg group achieved ACR20 compared with 28% (n=48) of participants in the placebo group (P <.0001 for both doses vs placebo).


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A DAS28-CRP of 3.2 or less was achieved by 43% (n=71) of participants in the upadacitinib 15-mg group and 42% (n=70) of participants in the 30-mg group compared with 14% (n=24) of participants in the placebo group (P <.0001 for both doses vs placebo).

Up to 12 weeks, the number of participants who experienced adverse events was similar between the placebo group (56%; n=95) and the upadacitinib 15-mg group (55%; n=91). The upadacitinib 30-mg group had a higher number of adverse events (67%, n=111). The most common adverse events were upper respiratory tract infection, nasopharyngitis, and worsening of RA.

In the placebo group, no serious adverse events were reported, whereas 12 were reported in the upadacitinib 30-mg group and 8 in the 15-mg group. Of these, 1 case of pulmonary embolism, 3 malignancies, 1 major adverse cardiovascular event, and 1 death were reported among participants in the upadacitinib groups.

In a second study,2 the phase 3 trial (ClinicalTrials.gov identifier: NCT02675426) included participants aged 18 years or older with active RA for 3 months or longer who had received csDMARDs for at least 3 months with a stable dose for at least 4 weeks before study entry and had an inadequate response to at least 1 of the following: methotrexate, sulfasalazine, or leflunomide (n=661). Participants were assigned to receive once-daily oral extended-release upadacitinib 15 mg (n=221), upadacitinib 30 mg (n=219), or placebo (n=221) for 12 weeks. The primary end points were the proportions of participants who achieved ACR20 and DAS28-CRP at 12 weeks.

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At 12 weeks, 64% (n=141) of participants in the upadacitinib 15-mg group and 66% (n=145) of participants in the 30-mg group achieved ACR20 compared with 36% (n=79) of participants in the placebo group (P <.0001 for both doses vs placebo).

A DAS28-CRP of 3.2 or less was achieved by 48% (n=107) of participants in the upadacitinib 15-mg group and 48% (n=105) of participants in the 30-mg group compared with 17% (n=38) of participants in the placebo group (P <.0001 for both doses vs placebo).

The rate of adverse events at 12 weeks was 49% in the placebo group (n=108), 57% in the upadacitinib 15-mg group (n=125), and 54% in the upadacitinib 30-mg group (n=118). The most common adverse events were nausea, nasopharyngitis, upper respiratory tract infection, and headache.

Of the serious adverse events reported, there were 3 herpes zoster infections (1 in each group), 1 primary varicella zoster virus infection in the upadacitinib 30 mg group, 2 malignancies in the upadacitinib 30 mg group, 1 adjudicated major adverse cardiovascular event in the upadacitinib 30-mg group, and 5 serious infections (1 in the placebo group, 1 in the upadacitinib 15-mg group, and 3 in the upadacitinib 30-mg group).

Both studies were funded by AbbVie Inc.

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References

  1. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513-2524.         
  2. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512.