Background/Purpose: Serum ferritin (FERR) is a recognized marker of immune activation and a key laboratory feature of anti-MDA5 Dermatomyositis (DM). It has been increasingly studied as a potential biomarker of disease activity, particularly due to its association with complications like rapidly progressive interstitial lung disease (RP-ILD), treatment response and prognosis. Its role in Antisynthetase Syndrome (ASS) remains less clear. This study aimed to assess the longitudinal variation of FERR and its correlation with disease activity in anti-MDA5 DM and, secondarily, to explore whether similar patterns were observed in matched anti-Jo1 ASS patients.

Methods: We retrospectively included adult patients with active anti-MDA5 DM or anti-Jo1 ASS (according to 2017 ACR/EULAR and Connor’s criteria, respectively), all with ILD, evaluated across four Italian Myositis Centers. Inclusion criteria required demographic, clinical and serological data at baseline and at least two follow-up timepoints (3, 6, 12, and 18 months – t1, t2, t3 and t4, respectively). Disease activity was assessed by Physician Global Activity (PhGA). FERR, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and creatinkinase (CK) were collected at each timepoint. Patients were treated according to local clinical practice, without a standardized therapeutic protocol.

Results: A total of 23 patients were included (11 DM, 12 ASS). Despite ASS patients exhibiting more extensive organ involvement – with 66% of them presenting ≥ 4 affected domains, compared to 36% in the DM group – baseline FERR was significantly higher in DM patients (median 312 vs 82 ng/mL, p = 0.007, image 1), while CK was increased in ASS (median 336 vs 101 U/L, p = 0.05). During follow-up, DM patients showed a progressive and significant reduction in FERR levels (image 2), with differences reaching statistical significance at 12 months (t3 – t0, p = 0.025) and 18 months (t4 – t0, p = 0.017). PhGA also significantly improved in DM group (t2 – t0, p = 0.019; t3 – t0, p = 0.013; t4 – t0, p = 0.002), closely mirroring the ferritin decline. In contrast, no significant changes in FERR were seen in ASS cohort, despite a parallel clinical improvement (t4 – t0, p = 0.005, image 3). CRP levels did not vary significantly in either group during follow-up and ESR showed fluctuating values without consistent trends.

Conclusion: To the best of our knowledge, this is the first study comparing longitudinal FERR trends in anti-MDA5 DM and anti-Jo1 ASS with lung involvement. In the DM cohort, FERR significantly declined over time along with disease activity, thus supporting its role as a biomarker in this subtype of myositis. The absence of a similar trend in ASS suggests differing inflammatory pathways and reinforces the need for disease-specific biomarkers. These findings may be especially relevant in the management of DM patients with lung involvement, where early and reliable indicators of response are urgently needed. Despite limitations (small sample size, short follow-up, treatment heterogeneity), we believe that these findings offer preliminary evidence for the utility of FERR in monitoring anti-MDA5 DM: further prospective studies are needed to validate our results in larger and more diverse cohorts.

Image 1: serum ferritin levels at baseline.

Image 2: serum ferritin levels during follow-up.

Image 3: PhGA trend during follow-up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ferritin-trends-differentiate-anti-mda5-dermatomyositis-from-anti-jo1-antisynthetase-syndrome/