Towards new treatment options for psoriatic arthritis
medwireNews: Clinical trial results presented at the Annual European Congress of Rheumatology (EULAR) 2017 in Madrid, Spain, highlight the growing number of potential treatments for psoriatic arthritis (PsA).
Philip Mease (University of Washington School of Medicine, Seattle, USA) outlined the results of the OPAL Broaden study, a phase III randomized controlled trial of tofacitinib or adalimumab versus placebo for the treatment of patients with active PsA who had an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs).
The researchers found that a significantly greater proportion of 107 patients receiving tofacitinib 5 mg twice daily and 104 patients receiving the Janus kinase inhibitor at a dose of 10 mg twice daily achieved at least a 20% improvement in ACR criteria (ACR20) at 3 months compared with 105 patients receiving placebo, at 50% and 61% versus 33%.
Furthermore, the ACR20 response rate at 3 months was significantly greater among the 106 patients receiving 40 mg adalimumab twice weekly compared with those in the placebo group (52 vs 33%). The frequency of serious adverse events (AEs) and treatment discontinuations due to AEs was “low and similar across treatment groups,” said Mease.
Speaking to medwireNews, Mease concluded that “[tofacitinib] will be a solid entrant into the PsA market and it will be a new mechanism to what we’ve seen before. It will appeal to patients who want to use oral medication.”
The monoclonal antibody guselkumab “is the first biologic that specifically targets IL[interleukin]-3 to demonstrate efficacy in PsA,” said Atul Deodhar (Oregon Health & Science University, Portland, USA), who presented the results of a phase IIa study.
Deodhar and colleagues found that 58.0% of 100 patients treated with 100 mg guselkumab every 8 weeks had an ACR20 response at week 24, compared with 18.4% of 49 placebo-treated patients, a significant difference.
And a significantly higher proportion of patients treated with guselkumab versus placebo achieved a 75% reduction in the Psoriasis Area and Severity Index (PASI) score at week 24, at 78.6% versus 12.5%.
Guselkumab was “well tolerated with no unexpected safety findings,” said Deodhar.
And he told the press that the IL-3 inhibitor “appears to be a promising new treatment of PsA.”
The 52-week results of the ACTIVE study of apremilast monotherapy versus placebo among biologic-naïve patients with active PsA were presented by Peter Nash, from the Rheumatology Research Unit in Sunshine Coast, Queensland, Australia.
“Apremilast now has quite an extensive clinical trial program,” said Nash, noting that the phosphodiesterase 4 inhibitor has been tested in patients with and without prior DMARD or biologic treatment.
After 16 weeks of treatment with 30 mg apremilast twice daily or placebo, patients who did not have a 10% improvement in swollen and tender joint counts were switched to apremilast, and all patients received apremilast from week 24.
At the 16-week follow-up, 38.2% of 110 participants in the apremilast arm versus 20.2% of 109 patients in the placebo arm had an ACR20 response, a significant difference. And there was “progressive improvement over time” of ACR20 responses among the 171 patients remaining in the study for up to a year, said Nash, noting that the proportions of patients with ACR20, 50, and 70 responses at week 52 were 67.1%, 36.7%, and 21.3%, respectively.
The incidence of AEs was “generally similar” between the two treatment arms during the placebo-controlled phase, and the researchers did not observe an increase in the incidence or severity of AEs with longer-term exposure to apremilast.
Nash concluded that “apremilast monotherapy improves the signs and symptoms of psoriatic arthritis,” with efficacy improving over time, and that “the adverse event profile was very similar” to that observed in previous studies.
As reported previously by medwireNews, the SPIRIT-P2 trial results showed that ixekizumab treatment significantly improves the proportion of patients with an ACR20 response at week 24 compared with placebo among patients with an inadequate response to tumor necrosis factor (TNF) inhibitors.
Désirée van der Heijde presented the 52-week radiographic outcomes of ixekizumab-treated patients from the SPIRIT-P1 trial, a phase III study of ixekizumab or adalimumab versus placebo in biologic-naïve patients with active PsA. In the extension period, 381 patients remaining in the study were randomly assigned to receive ixekizumab every 2 or 4 weeks until week 52.
Participants receiving ixekizumab every 2 weeks throughout the study experienced a mean change in total Sharp Score (mTSS) of 0.09 points from baseline to week 52, while those receiving the drug every 4 weeks for the study duration had a mean change of 0.54 points.
And for patients who switched from placebo or adalimumab to ixekizumab in the extension phase, changes in mTSS scores from baseline ranged from –0.03 to 0.41 points. In probability plot analyses, approximately 20% of the participants experienced any progression, said van der Heijde.
These findings suggest that “the majority of patients exhibited either no or minimal structural progression” over the 52-week study period, she concluded.
Iain McInnes (University of Glasgow, UK) outlined the results of the extension phase of the FUTURE 2 study, which suggest sustained benefits of treatment with secukinumab among patients with active PsA.
Previous data from the study – in which patients were randomly assigned to receive the IL-17A inhibitor, at a dose of 300, 150, or 75 mg, or placebo – have demonstrated the efficacy of secukinumab in patients with PsA for up to 52 weeks, said McInnes.
ACR20 response rates were sustained through to week 104 among secukinumab-treated patients, with rates of 69.4% for the 100 participants in the 300 mg group, 64.4% for the 100 patients in the 150 mg group, and 50.3% for the 99 patients receiving the drug at a dose of 75 mg. The corresponding ACR50 response rates were 50.6%, 36.0%, and 28.2%.
“The 75 mg dose is not an approved dose for this medication,” emphasized McInnes, noting that the ACR50 response was “not at a satisfactory level” among patients receiving this dose.
ACR20 and ACR50 responses were sustained over 104 weeks regardless of prior treatment with TNF inhibitors, and skin responses were “very robust,” said McInnes. The safety profile was “consistent with that reported previously in phase III trials in PsA, psoriasis and ankylosing spondylitis,” he added.
And McInnes concluded that “both 150 and 300 mg doses of secukinumab provide sustained responses through 2 years in those patients who continue on medication.”
Commenting on the implications of these results, study co-author Oliver FitzGerald (University College Dublin, Ireland) told medwireNews that “abatacept is a useful alternative consideration for patients who have failed initial biologic treatment with anti-TNF therapy.” You can watch the full interview here:
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