LONDON, United Kingdom — The oral Janus kinase (JAK) inhibitor tofacitinib (Xeljanz, Pfizer) might be a new option for patients with ankylosing spondylitis, according to results from a new phase 2 study.
"This is the first study to demonstrate the efficacy of a JAK inhibitor in patients with ankylosing spondylitis," said Desiree van der Heijde, MD, from the Leiden University Medical Centre in the Netherlands.
"Right now, only about one-quarter of patients with ankylosing spondylitis achieve sustained remission, even with targeted molecular therapies, which is not a very high remission rate," she told Medscape Medical News. "It would be good to have another drug to treat the disease."
"Our data are quite consistent, especially if you look at objective measures of response," she pointed out. "We saw no new safety signals, beyond those we've seen in other rheumatic diseases, so I think the data are promising."
The study results were presented here at the European League Against Rheumatism Congress 2016.
In their placebo-controlled double-blind study, Dr van der Heijde and her colleagues evaluated dose-response to tofacitinib in patients with active ankylosing spondylitis and assessed safety and efficacy.
Patients were randomized to one of three doses of tofacitinib — 2 mg, 5 mg, or 10 mg, all administered twice a day — or to placebo for 12 weeks. Patients were then followed for an additional 4 weeks. The analysis involved 52 patients in the tofacitinib groups and 51 patients in the placebo group.
Patients were assessed with MRI at baseline and after 12 weeks of treatment.
At baseline, mean disease duration was 6.3 years and mean Bath Anklyosing Spondylitis Disease Activity Score (BASDAI) score was 6.7. "As expected, over 85% of patients were HLA-B27 positive," Dr van der Heijde pointed out.
A sizeable proportion of patients were also taking a disease-modifying antirheumatic drug at study entry.
The primary efficacy end point was ASAS20, defined as an improvement of at least 20% in response criteria, at week 12.
"The predicted dose of 5 mg twice daily had a response rate of 63%, which was almost 23% higher than the response rate in placebo controls," Dr van der Heijde reported. The 10 mg twice-daily dose "had a high response rate as well."
In fact, the ASAS20 response rate was 15.8% higher in the 2 mg group than in the placebo group, 22.9% higher in the 5 mg group, and 27.3% higher in the 10 mg group.
Table. Response Rates at 16 Weeks
|Criteria||Tofacitinib 2 mg Group||Tofacitinib 5 mg Group||Tofacitinib 10 mg Group||Placebo Group|
"At week 12, there was clear dose-response in all clinical outcome measures," said Dr van der Heijde.
There was improvement in MRI Spondyloarthritis Research Consortium of Canada (SPARCC) scores from baseline to week 12 with tofacitinib, particularly in the 5 mg and 10 mg groups; the change was minimal in the 2 mg group. In the placebo group, there was almost no change in SPARCC scores over the study period.
Between the 5 mg and 10 mg groups, the differences in improvement in SPARCC sacroiliac joint and spine scores were minimal, as was the difference in clinical efficacy, Dr van der Heijde explained.
There was no difference in the safety profile between any of the tofacitinib groups and the placebo group.
Although some dose-dependent changes in laboratory outcomes were seen in the tofacitinib groups, levels had returned to baseline by the end of the study, and very few patients in the tofacitinib groups discontinued treatment.
"We now have positive data on at least one JAK inhibitor in this disease," said Dr van der Heijde.
New medications for the treatment of most rheumatic diseases are always needed. "We never have enough," said Juergen Braun, MD, from Rheumazentrum Ruhrgebiet in Herne, Germany.
During the same session, Dr Braun presented first results from the MEASURE 1 trial, evaluating the long-term effects of interleukin-17A inhibition with secukinumab in patients with ankylosing spondylitis.
Secukinumab was administered in one of two doses in the trial — 75 mg and 150 mg — but there were no major differences in radiographic results between the groups, so the researchers pooled the data.
"The mean change in the modified Stoke Ankylosing Spondylitis Spine Score at 104 weeks was only 0.30 in the group overall, although radiographic changes were more pronounced in males, in patients with syndesmophytes at baseline, and in those with an elevated C-reactive protein," Dr Braun reported.
Given that "no radiographic progression was observed in approximately 80% of patients who received secukinumab over 104 weeks, data suggest that there may be a lower rate of structural progression with secukinumab, compared with earlier intervention studies, although this remains to be proven," he added.
"From my perspective, these data justify further investigation of JAK inhibitors in ankylosing spondylitis in larger phase 3 trials," said Denis Poddubnyy, MD, from Charité Universitätsmedizin in Berlin.
"We see the effect of tofacitinib in the primary end-point analysis, in the observed data, and in the MRI data," he told Medscape Medical News in an email.
"This is a strong signal, and suggests that JAK blockade might be effective in ankylosing spondylitis at least on the same level as currently approved biologics, including tumor necrosis factor and interleukin-17 blockers," he added.
Dr van der Heijde reports serving as a consultant for AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, sanofi-aventis, UCB, and Vertex. The MEASURE-1 study was funded by Novartis. Dr Braun reports financial relationships with AbbVie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, sanofi-aventis, and UCB.
European League Against Rheumatism (EULAR) Congress 2016: Abstracts OP0001 and OP0002. Presented June 8, 2016.
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Cite this: Oral JAK Inhibitor Promising in Ankylosing Spondylitis - Medscape - Jun 09, 2016.