Background/Purpose: Diffusion weighted imaging (DWI) in muscle magnetic resonance imaging is an underutilized, quantitative assessment tool in idiopathic inflammatory myopathies (IIM). It is not uncommon for patients with dermatomyositis (DM) to have normal creatine kinase (CK) levels but have objective muscle weakness on exam. Muscle MRI can detect muscle edema even in subclinical myositis and has the potential to quantify the degree of inflammation in muscles. The purpose of this study was to examine the utility of DWI in thigh muscle MRI in a proof of concept open label clinical trial of tofacitinib in refractory dermatomyositis. 

Methods: Ten patients with refractory DM were enrolled at one center and given tofacitinib 11mg XR daily for 12 weeks. The key exploratory endpoint evaluated for this study was differences in diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping after 12 weeks of treatment with tofacitinib. Additional sequences included T1-weighted and short tau inversion recover sequence (STIR) of both hips and thighs. For the ADC map, three region of interest (ROIs) were drawn in skeletal muscles and the minimum and average ADC values were recorded by one reader. The muscles were selected based on qualitative assessment of maximal elevated signal on DWI.  The differences between means ADC maps were examined using the paired sample t-test for continuous variables. Manual muscle testing -8 (MMT-8) was performed prior to and following therapy and also compared to changes observed in mean ADC values. A p-value ≤ 0.05 was considered statistically significant.

Results: Ten patients with pre- and post-treatment muscle MRIs were analyzed. Mean age at enrollment was 45.6 + 10.6 years and 7 of 10 (70%) were female. A total of 20 muscle MRIs were analyzed by ADC mapping in 640 unique muscle groups. Only 4 of the 10 patients had evidence of muscle edema on STIR imaging in at least 1 muscle group. The most commonly affected muscle groups at baseline on STIR were the rectus femoris, gracilis, vastus lateralis, sartorius, and adductor longus and magnus. The overall mean ADC for these 4 patients’ pelvic and thigh muscles were 1.41 ± 0.2 and 1.53 ± 0.2 at baseline. There was a statistically significant decrease in the ADC value from baseline to 12 weeks in the rectus femoris (p=0.02), vastus lateralis, (p=0.02), vastus medialis (p=0.007), vastus intermedius (p=0.02), gracilis (p=0.02), sartorius (p=0.007), adductor longus (p=0.03) and magnus (p=0.03)   In these 4 patients, 11 out of 32 (34.5%) of the muscles imaged showed significant improvement by MRI. Two of 4 patients who had a low MMT-8 at baseline had improved MMT-8 at 12 weeks which corresponded to a decrease in mean ADC map values.

Conclusion: In this post-hoc analyses of an open label pilot trial of tofacitinib in skin-predominant refractory dermatomyositis, diffusion weight imaging with ADC mapping was able to demonstrate quantifiable improvements in edema after 12 weeks of treatment. Even those who did not have low MMT-8 at entry but had subclinical muscle edema demonstrated improvement on DWI highlighting that muscle MRI can be more sensitive in detecting change. Quantitative muscle MRI can be a valuable surrogate endpoint in future IIM clinical trials.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diffusion-weighted-imaging-in-muscle-mri-can-detect-quantitative-improvements-in-muscle-edema-a-post-hoc-analyses-of-the-study-of-tofacitinib-in-refractory-dermatomyositis/