After 12 weeks, nearly one-third of patients with ankylosing spondylitis (AS) who received tofacitinib demonstrated a substantial reduction in spinal inflammation as measured by minimally important changes on magnetic resonance imaging (MRI). Regardless of treatment group, patients who achieved minimally important changes also outperformed patients who did not in terms of clinical disease indices. Findings from this post hoc analysis of a 12-week, phase 2, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT01786668) were published in Rheumatology.
The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system provides clinicians an objective assessment of sacroiliac (SI) joint and spine inflammation using MRI, and minimally important changes can determine meaningful change in patients with AS. Investigators examined the percentage of participants achieving minimally important change with tofacitinib or placebo, as well as whether this achievement correlated with clinical improvements.
Of the 207 biologic-naive individuals with AS who were originally enrolled, 164 with available MRI data were included in the study. Participants were randomly assigned to receive 2 mg, 5 mg, or 10 mg of tofacitinib or placebo twice daily. Cutoffs for SPARCC minimally important changes were ≥2.5 and ≥5 for the SI joint and spine, respectively, and MRI remission was defined as <2 and <3, respectively. Clinical outcomes, including the Assessment of Spondyloarthritis International Society 20% improvement (ASAS20), were evaluated at 12 weeks.
Compared with placebo, a larger percentage of tofacitinib-treated patients achieved SPARCC minimally important changes when taking 2 mg, 5 mg, and 10 mg twice daily for the SI joint (28.6%, 38.6%, and 29.6% vs 11.8%, respectively) and the spine (29.3%, 36.4%, and 40.9% vs 11.8%, respectively). Participants who achieved minimally important changes for the SI joint or spine were also more likely to achieve ASAS20, regardless of whether they received 2 mg, 5 mg, or 10 mg tofacitinib or placebo (SI joint, 75.0%, 88.2%, 69.2%, and 75.0%; spine, 91.7%, 85.7%, 72.2%, and 75.0%; respectively) compared with participants who did not achieve minimally important changes (SI joint, 51.7%, 84.0%, 58.1% and 48.3%; spine, 46.4%, 85.7%, 53.8% and 48.3%; respectively). Other efficacy assessments showed similar numerically larger clinical responses for participants achieving minimally important changes vs participants who did not.
No participants receiving placebo achieved minimally important changes in both the SI joint and spine, compared with 7.3%, 18.2%, and 6.8% of participants in the 2 mg, 5 mg, and 10 mg tofacitinib groups, respectively. Pooled analysis of the 5 mg and 10 mg tofacitinib groups vs placebo revealed significantly higher percentages of patients achieving minimally important changes in the SI joint (34.1% vs 11.8%), spine (38.6% vs 11.8%), and both sites (12.5% vs 0.0%; P <.05 for all comparisons). MRI remission in the SI joint was seen in 40.5%, 36.4%, 40.9%, and 52.9% of participants in the 2 mg, 5 mg, or 10 mg and placebo groups, respectively, and in 40.5%, 25.0%, 38.6%, and 32.4% of patients in the spine, respectively.
Study limitations included the short duration, small sample size, reporting of mostly numerical differences, and missing MRI data for some patients.
Although numerically greater percentages of participants taking tofacitinib achieved minimally important changes in spinal inflammation and participants who reached minimally important changes also achieved numerically larger clinical improvements in other clinical measures, most comparisons did not reach statistical significance. The lack of a clear and strong correlation between the achievement of minimally important change and clinical end points demands further exploration in longer-term studies involving more participants. The authors cautioned, “the [minimally important change] for SPARCC scores may not be suitable for use as a minimum clinically important difference, as reduction in inflammation does not appear to be directly linked to improvements in clinical assessments and patient outcomes.”
Please see original article for a full list of disclosures.
Maksymowych WP, Heijde DVD, Baraliakos X, et al. Tofacitinib is associated with attainment of the minimally important reduction in axial magnetic resonance imaging inflammation in ankylosing spondylitis patients [published online April 26, 2018]. Rheumatology (Oxford). doi:10.1093/rheumatology/key104