MADRID -- Tofacitinib (Xeljanz) treatment was associated with significant benefits on spinal and sacroiliac joint MRI changes, and patients who achieved MRI minimally important changes (MIC) also showed clinical benefits, a new study found.
Approximately three times as many patients receiving tofacitinib had an MIC on MRI for the sacroiliac joints by week 16 (34.1% versus 11.8%, P<0.05) versus placebo, and also for the spine (38.6% versus 11.8%, P<0.01), according to Walter P. Maksymowych, MD, of the University of Alberta in Edmonton, Canada. In addition, 12.5% of those receiving tofacitinib had MICs for both sacroiliac joints plus spine compared with none receiving placebo (12.5% versus 0%, P<0.01).
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this randomized trial of the JAK inhibitor tofacitinib showed promising results in the treatment of ankylosing spondylitis.
- Be aware that patients enrolled in this trial had inadequate responses to NSAIDs.
Patients who achieved the minimally important MRI scores also more often had 20% and 40% improvement on the criteria of the Assessment of Spondyloarthritis (ASAS) International Society. For instance, among patients in the pooled 5- and 10-mg twice daily tofacitinib groups, ASAS20 responses were seen in 90.9%% of those who had a MIC of at least 2.5 for the sacroiliac joints and at least 5 for the spine at week 12, compared with 70.7% of those not achieving the MIC, Maksymowych reported in a poster session at the here, organized by the European League Against Rheumatism.
In addition, 72.7% of patients in the pooled 5- and 10-mg groups who had MIC responses for both sacroiliac joints and spine at week 12 had ASAS40 responses, compared with 45.3% of those without MIC on MRI, he said.
Tofacitinib is an oral JAK inhibitor that preferentially inhibits signaling through the JAK1 and 3 pathways. To determine the effects of tofacitinib on MRI scores according to the rating system of the Spondyloarthritis Research Consortium of Canada (SPARCC), and whether achieving MIC on imaging correlated with clinical responses, he and his colleagues conducted a post-hoc analysis of a 16-week phase II study in which patients received tofacitinib in doses of 2, 5, or 10 mg, or placebo, all given twice daily.
The study included 207 patients with radiographic sacroiliitis and active disease based on a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 4 or higher and a back pain score of at least 4. All had had an inadequate response or intolerance to nonsteroidal anti-inflammatory drug treatment. Methotrexate, sulfasalazine, and stable oral corticosteroids were allowed.
MRI data at 12 weeks were available for 164 patients and were included in this analysis. The MIC for SPARCC has been established as at least 2.5 for the sacroiliac joints and 5 for the spine.
Most study participants were white men, and mean age was 42. Median disease duration was 3 years. Mean baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) was 3.7, mean baseline BASDAI was 6.8, and mean baseline Bath Ankylosing Spondylitis Functional Index was 5.7.
Changes on SPARCC scores for the sacroiliac joints at week 12 were -2.2 for the tofacitinib 2-mg group, -3.5 for the 5-mg group, and -3.6 for the 10-mg group compared with -0.7 for the placebo group. For SPARCC spine scores, the changes were -3.2, -5.5, and -6.7 versus -0.8, respectively.
Among patients who had achieved an MIC for the sacroiliac joints at week 12, changes from baseline on BASDAI were -3.5 in the pooled 5- and 10-mg groups compared with -2.5 in the placebo group, a difference that was statistically significant (P<0.05), while among those who had not achieved an MIC for the sacroiliac joints, the changes were -2.7 and -1.8, which did not represent a significant difference.
For spine, similar results were seen among those who did and did not achieve MICs at week 12, with changes of -3 for each in the pooled 5- and 10-mg groups.
For overall back pain, changes were -3.6 at week 12 for the pooled 5- and 10-mg groups who had an MIC for the sacroiliac joints and -2.8 in those without an MIC. Changes among those who had an MIC for the spine were -3.5 compared with -2.9 for those without an MIC.
"Tofacitinib-treated patients who achieved MIC for MRI inflammation had greater clinical response rates versus those not achieving MIC," Maksymowych concluded.
Disclosures
The study was sponsored by Pfizer, maker of tofacitinib.
Maksymowych reported financial relationships with Pfizer, AbbVie, Sanofi, UCB, Eli Lilly, Janssen, Merck, Novartis, and UCB.
Primary Source
European League Against Rheumatism
Maksymowych W, et al "Tofacitinib treatment is associated with attainment of the minimally important reduction in axial MRI inflammation in patients with ankylosing spondylitis" EULAR 2017; Abstract THU352.