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21-02-2019 | Spondyloarthropathies | Feature | Article

Updated June 2022

Trials of JAK inhibitors in spondyloarthritis: A round-up

Author: Claire Barnard

Findings from a number of randomized controlled trials have demonstrated that Janus kinase (JAK) inhibitors – including tofacitinib and filgotinib – may be a promising drug class for the treatment of spondyloarthritis, and tofacitinib is now approved for psoriatic arthritis (PsA) in the USA and Europe. To accompany our interview with Dafna Gladman on the role of JAK inhibitors in PsA therapy, here is a round-up of the completed and ongoing clinical trials investigating JAK inhibitors in patients with PsA and axial spondyloarthritis (axSpA).

Tofacitinib (JAK1/3 inhibitor)

Findings from the seven published and ongoing clinical trials of tofacitinib for the treatment of PsA and ankylosing spondylitis are summarized in this article.

Filgotinib (selective JAK1 inhibitor)

EQUATOR: PsA

Phase 2

Patient population: Moderate-to-severe PsA and an insufficient response or intolerance to at least one conventional DMARD

Treatment groups: Filgotinib 200 mg/day or placebo for 16 weeks

Status: Published

https://clinicaltrials.gov/ct2/show/NCT03101670

As reported at the 2018 ACR/ARHP Annual Meeting in Chicago, Illinois, USA, and published in The Lancet in October 2018, the EQUATOR trial investigated the efficacy and safety profiles of the selective JAK1 inhibitor filgotinib in PsA patients from seven European countries. A significantly higher proportion of patients treated with filgotinib compared with placebo achieved an ACR20 response at week 16 (80 vs 33%), and the investigators say that no new safety concerns were identified.

Related news story: Filgotinib shows promise in psoriatic arthritis treatment

TORTUGA: Ankylosing spondylitis

Phase 2

Patient population: Ankylosing spondylitis and an inadequate response or intolerance to at least two nonsteroidal anti-inflammatory drugs (NSAIDs)

Treatment groups: Filgotinib 200 mg/day or placebo for 12 weeks

Status: Published

https://clinicaltrials.gov/ct2/show/NCT03117270

Also published in The Lancet in October 2018, the results of the TORTUGA trial suggest that ankylosing spondylitis patients who are treated with filgotinib may experience greater reductions in disease activity than those given placebo. The average reduction in ASDAS from baseline to week 12 was 1.47 points in the filgotinib group versus 0.57 points in the placebo group, a significant difference, and patients experienced improvements in disease activity after 1 week of treatment.

Related news story: Further investigation of filgotinib warranted in ankylosing spondylitis patients

Upadacitinib (selective JAK1 inhibitor)

SELECT-PsA 1

Phase 3

Patient population: Moderate-to-severe PsA and an inadequate response to at least one nonbiologic DMARD

Treatment groups: Upadacitinib 15 mg or 30 mg/day, placebo, or adalimumab 40 mg every other week

Status: Results reported

https://clinicaltrials.gov/ct2/show/NCT03104400

As reported at the EULAR 2020 E-Congress, ACR20 response rates at week 12 were significantly higher among patients treated with upadacitinib 15 mg or 30 mg versus placebo, at 71% and 79% versus 36%, respectively. 

The ACR20 response rate in the adalimumab arm was 65%. There was noninferiority between both doses of upadacitinib and adalimumab, while the higher dose of upadacitinib gave rise to significantly higher ACR20 response rates than adalimumab.

Related news story: Upadacitinib shows promise for PsA

SELECT-PsA 2

Phase 3

Patient population: Moderate-to-severe PsA and an inadequate response to at least one biologic DMARD

Treatment groups: Upadacitinib 15 mg or 30 mg/day, or placebo

Status: Results reported

https://clinicaltrials.gov/ct2/show/NCT03104374

Also reported at the EULAR 2020 E-Congress, SELECT-PsA-2 demonstrated significantly higher ACR20 response rates at week 12 among patients treated with upadacitinib 15 mg or 30 mg versus placebo (57 and 64 vs 24%). The presenting author said that SELECT-PsA-2 demonstrated efficacy of upadacitinib in all core clinical domains of psoriatic arthritis.

Related news story: Upadacitinib shows promise for PsA

SELECT-AXIS 1: Ankylosing spondylitis

Phase 2/3

Patient population: Biologic-naïve patients with ankylosing spondylitis and an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs

Treatment groups: Upadacitinib 15 mg/day or placebo

Status: Published

https://clinicaltrials.gov/ct2/show/NCT03178487

The SELECT-AXIS 1 results were published in The Lancet and reported at the ACR/ARP Annual Meeting in Atlanta, Georgia, USA, in November 2019. Patients treated with upadacitinib had significantly higher ASAS40 response rates at week 14 than those given placebo (52 vs 26%). Participants in the upadacitinib arm also experienced significantly greater decreases in Spondyloarthritis Research Consortium of Canada magnetic resonance imaging spine and sacroiliac joint scores compared with those given placebo, and no new safety signals were observed.

Related news story: Upadacitinib demonstrates potential for ankylosing spondylitis

Video interview: Lead investigator Désirée van der Heijde discusses the SELECT-AXIS 1 results

SELECT-AXIS 2: AxSpA

Phase 3

Patient population: Ankylosing spondylitis with an inadequate response to biologic DMARDs or nonradiographic axSpA with objective signs of inflammation

Treatment groups: Upadacitinib 15 mg/day or placebo

Status: Results reported

https://clinicaltrials.gov/ct2/show/NCT04169373

SELECT-AXIS 2 was reported at the EULAR 2022 Congress in Copenhagen, Denmark, separated into two presentations according to whether patients had ankylosing spondylitis or nonradiographic axSpA. In accordance with the SELECT-AXIS 1 trial, the SELECT-AXIS 2 investigators demonstrated significantly higher ASAS40 response rates at week 14 among participants treated with upadacitinib versus placebo, in both the ankylosing spondylitis and nonradiographic axSpA groups.

Related news story: SELECT-AXIS 2: Upadacitinib shows promise for axSpA

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