Following the approval of tofacitinib as the first Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis by the US FDA in 2012, the drug has also demonstrated efficacy in patients with spondyloarthritis. The majority of these trials were conducted in patients with psoriatic arthritis (PsA), and the indication of tofacitinib has now been expanded to include PsA in the USA and Europe.
Here is a quick-reference guide to the published and ongoing clinical trials of tofacitinib for the treatment of spondyloarthritis.
OPAL Broaden: PsA
Patient population: Active PsA and an inadequate response to conventional DMARDs
Treatment groups: Tofacitinib 5 mg or 10 mg twice daily, adalimumab, or placebo, all given alongside a stable dose of a single conventional DMARD (methotrexate, sulfasalazine, or leflunomide)
The findings from OPAL Broaden, published in The New England Journal of Medicine in October 2017, showed that patients treated with tofacitinib 5 mg or 10 mg were significantly more likely to achieve at least a 20% improvement in ACR criteria (ACR20) after 3 months of treatment than placebo-treated patients, with corresponding rates of 50% and 61% versus 33%. The ACR20 response rate was 52% in the adalimumab group.
Patients in the tofacitinib 5 mg and 10 mg groups also experienced significantly greater reductions in mean Health Assessment Questionnaire–Disability Index (HAQ–DI) scores than those in the placebo group (0.35 and 0.40 versus 0.18 points).
Related news story: Towards new treatment options for psoriatic arthritis
OPAL Beyond: PsA
Patient population: Active PsA and an inadequate response to TNF inhibitors
Treatment groups: Tofacitinib 5 mg or 10 mg twice daily, or placebo, all given alongside a stable dose of a single conventional DMARD
The OPAL Beyond results were also published in The New England Journal of Medicine in October 2017. The investigators demonstrated that ACR20 response rates at the 3-month follow-up were significantly higher among patients treated with tofacitinib 5 mg or 10 mg versus placebo, at 50% and 47% versus 24%, respectively. Similarly to the OPAL BROADEN results, tofacitinib-treated patients had significantly greater improvements in HAQ–DI scores, with average reductions of 0.39 and 0.35 points versus 0.14 points for the placebo group.
Related news story: Phase 3 results support tofacitinib for psoriatic arthritis
Patient population: Japanese patients with moderate-to-severe plaque psoriasis and/or psoriatic arthritis
Treatment groups: Tofacitinib 5 mg or 10 mg twice daily
The results of this trial, published in The Journal of Dermatology in February 2016, demonstrated that 62.8% of patients receiving tofacitinib 5 mg and 72.7% of those given the 10 mg dose achieved at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) score from baseline. All PsA patients achieved an ACR20 response at week 16.
OPAL Balance: PsA
Patient population: Patients with active PsA who previously participated in the OPAL Broaden or OPAL Beyond studies
Treatment groups: Tofacitinib 5 mg or 10 mg twice daily, plus a substudy of the 5 mg twice daily dose given with methotrexate or placebo
This long-term open-label extension study was designed to evaluate the safety, tolerability, and efficacy of tofacitinib for up to 36 months.
An interim analysis of OPAL Balance, published in Rheumatology and Therapy in June 2020, reported that the safety and efficacy profiles over an average treatment duration of 641 days were consistent with those of the previous phase 3 trials.
The methotrexate withdrawal substudy demonstrated that participants who switched to tofacitinib monotherapy after stable treatment with tofacitinib plus methotrexate had similar outcomes to those who continued with combination therapy. The least squares mean increase in PsA disease activity score was 0.23 points in the tofacitinib monotherapy group and 0.14 points in the combination arm; the corresponding increases in HAQ-DI were 0.04 and 0.02 points, with no significant between-group differences. These results were published in The Lancet Rheumatology in November 2020.
The final analysis of OPAL Balance, published in The Lancet Rheumatology in April 2021, demonstrated that tofacitinib has a consistent safety profile during up to 48 months of follow-up.
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Patient population: PsA patients with no response to at least two nonsteroidal anti-inflammatory drugs
Treatment groups: Tofacitinib 5 mg or 10 mg twice daily or methotrexate
This open-label study will assess the safety and efficacy of tofacitinib versus methotrexate in 110 adult patients in Bangladesh. The estimated completion date is February 2019.
NCT01786668: Ankylosing spondylitis
Patient population: Active ankylosing spondylitis and no prior biologic DMARD treatment
Treatment groups: Tofacitinib 2 mg, 5 mg, or 10 mg twice daily, or placebo
As reported in the Annals of the Rheumatic Diseases in January 2017, the proportion of patients achieving at least a 20% improvement in Assessment of SpondyloArthritis International Society (ASAS) criteria at week 12 was 51.9%, 80.8%, and 55.8% in the tofacitinib 2 mg, 5 mg, and 10 mg groups, respectively. By comparison, 41.2% of placebo-treated patients achieved an ASAS20 response. Although all active treatment groups had numerically higher ASAS20 response rates than the placebo group, the difference only reached statistical significance with tofacitinib 5 mg.
NCT03502616: Ankylosing spondylitis
Patient population: Active ankylosing spondylitis and an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs
Treatment groups: Tofacitinib 5 mg or placebo twice daily
Status: Results reported; not yet publishsed
The findings from this trial were presented at the ACR Convergence 2020 virtual meeting. At the 16-week follow-up, 56.4% of patients treated with tofacitinib achieved the primary endpoint of ASAS20 response, compared with 29.4% of those given placebo, a significant difference.
Improvements in a range of secondary endpoints, including ASAS40 response rates, high-sensitivity C-reactive protein levels, and FACIT fatigue scores, were also significantly greater with tofacitinib versus placebo.
Related news story: Phase 3 trial demonstrates benefits of tofacitinib in ankylosing spondylitis
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