Approximately one-third of tofacitinib-treated AS patients experienced clinically meaningful reductions in spinal MRI inflammation at week 12. Patients achieving MIC for MRI inflammation had greater clinical response.

Ankylosing Spondylitis (AS) is a chronic, immune-mediated systemic inflammatory disease of the axial skeleton. MRI is the most widely used diagnostic tool to assess the inflammation in the SI joint and spine in patients with AS. MRI provides objective measure of inflammation and disease activity. Although MRI evaluations have been shown to be highly biased between treatments in studies of TNF inhibitors (TNFi) vs placebo, the association between changes in MRI and clinical outcomes is less well-defined. Minimally important change (MIC) can be a valuable concept to understand the number of patients showing meaningful change and can be applied to both clinical and imaging parameters so that associations in treatment responses can be evaluated more readily by clinicians.

A previous RCT study of adalimumab established the MICs for SPARCC SI joint and spine scores in patients with AS, with a global evaluation of change based on expert radiologist opinion as for the external anchor. Receiver-operating characteristic curves were used to define the MIC as ⩾2.5-point change for SI joint scores, and ⩾five-point change for spine scores.

Tofacitinib is an oral Janus kinase (JAK) inhibitor. It inhibits the signalling via JAK3 and JAK1 with functional selectivity over JAK2. As such, tofacitinib affects signalling via IL-17, IL-21 and IL-23, thereby reduce the inflammation. A previous study demonstrates the efficacy and safety of tofacitinib 5 and 10 mg in biologic-naïve patients with active AS. This study showed that tofacitinib 5 and 10 mg are twice daily (BID) provided greater efficacy vs placebo in reducing signs and symptoms of active AS over 12 weeks. MRI estimates showed significantly greater improvements from baseline in SPARCC SI joint and spine scores at week 12 with tofacitinib compared with placebo.

Rationale behind research:

Minimally important changes (MICs) for SPondyloArthritis Research Consortium of Canada (SPARCC) MRI scores are ⩾2.5 for SI joint and ⩾5 for spine. This post hoc analysis assessed achievement of MIC in SPARCC scores in biologic-naïve patients with AS treated with tofacitinib or placebo, and correlation with clinical responses.

Objective:

• To assess the proportion of patients achieving MIC in SPARCC SI joint and spine scores with tofacitinib vs placebo in patients with AS
• To determine whether achievement of MRI MIC corresponded with clinical improvements

Study outcomes:

• MIC in SPARCC SI joint and spine scores were assessed for patients with available MRI data (N = 164; 79%). Clinical endpoints at week 12, including Assessment of SpondyloArthritis international Society 20% improvement (ASAS20), were compared between patients achieving/not achieving MIC

Time period: Baseline, week 12, week 16

Of the 207 patients who participated in the phase 2 study, 164 patients had MRI data at baseline and follow-up (week 12 or study withdrawal) and were included in this analysis. Follow-up MRI data were not available for 43 patients (16 patients had no baseline MRI; data for five patients were not available due to technical issues; two patients withdrew prior to MRI completion; two patients had a visit deviation for MRI; no reason for missing MRI was provided for 18 patients).

• Patients achieving MIC in SPARCC SI joint and spine score:

Patients with MRI data at baseline and follow-up, after 12 weeks of treatment, greater proportions of patients achieved reduction in MRI inflammation according to the MIC in SPARCC SI joint scores with tofacitinib 2 mg BID (28.6%), 5 mg BID (38.6%) and 10 mg BID (29.5%) compared with placebo (11.8%) (Fig.1A). Similarly, greater proportions of patients achieved reduction in MRI inflammation according to the MIC in SPARCC spine scores with tofacitinib 2 mg BID (29.3%), 5 mg BID (36.4%) and 10 mg BID (40.9%) compared with placebo (11.8%) (Fig.1B). No placebo-treated patients achieved the MIC for both SPARCC SI joint and spine scores, compared with 7.3% of patients treated with tofacitinib 2 mg BID, 18.2% with 5 mg BID and 6.8% with 10 mg BID (Fig.1C). 

• Relationship between MIC for SPARCC scores and clinical assessments:

Greater proportion of patients who achieved the MIC in SPARCC SI joint or spine scores also achieved ASAS20 and ASAS40 responses compared with those patients who did not achieve the MIC in SPARCC SI jointor spine scores. A greater proportion of patients treated with tofacitinib who achieved the MIC in SPARCC SI joint or spine scores also achieved ASDAS MI and ASDAS CII compared with those patients who did not achieve MIC. However, the results were less clear for ASDAS ID and ASDAS moderate disease activity; clinical response was greater in patients achieving MIC in SI joint and spine scores in some, but not all, tofacitinib dose groups.

MRI and the SPARCC scoring system provide an objective diagnosis of inflammation and disease activity in AS patients. A previous 12-week phase 2 study showed significantly greater improvements from baseline in SPARCC SI joint and spine scores with tofacitinib 5 and 10 mg BID compared with placebo. The present study showed that a higher proportion of tofacitinib-treated patients achieved the MIC in both SPARCC SI joint and spine scores compared with placebo. Clinically about 30% of patients showed a reduction in spinal and SI joint inflammation with tofacitinib compared with 12% of placebo-treated patients.

In conclusion, The current analysis revealed that  ∼30% of AS patients treated with tofacitinib 2, 5 or 10 mg BID for 12 weeks showed significant reductions in axial MRI inflammation, and achieved MIC in SPARCC SI joint and spine scores compared with placebo. There was a trend for greater clinical responses among tofacitinib-treated patients who achieved MIC for MRI inflammation compared with those not completing MIC across all doses, although findings were limited by the small patient numbers in each group and differences between groups were small for some endpoints. Therefore, further evaluations are required in larger study populations and over a longer time-course to confirm if the MIC for SPARCC assessments is related to clinical outcomes and thus can be viewed as a true minimum clinically relevant difference in patients with AS in general, and those treated with tofacitinib especially.