Background/Purpose: Calcinosis represents a major challenge for patients with systemic sclerosis (SSc) for which there is no standard therapy. Minocycline has been proposed for treatment of refractory calcinosis in SSc (1,2). We assessed the possible benefit and adverse events (AE) of minocycline in cohort of SSc patients with calcinosis.

Methods: We reviewed patients with SSc, attending a large tertiary referral centre, that were treated with minocycline for severe calcinosis. Data collected included:  gender, scleroderma subtype, autoantibodies, dose and regime of administration of the minocycline, response to the treatment, AE, tolerability and proton pump inhibitors (PPI) use, if any, at the time of the treatment with minocycline. Treatment response was recorded either as subjective clinical improvement of the symptoms associated with calcinosis, or lack of response. 

Results: We identified 78 SSc patients treated with minocycline and this cohort reflects the spectrum of refractory calcinosis in SSc with typical ANA association (Table 1). Disease duration in the majority of the cases was longer than 10 years. The prescribed oral dose ranged from 50-200 mg daily and was administered in the majority of the cases for 6-12 weeks in repeated courses. Autoantibody status included typical SSc reactivity with 35.8% anti-centromere antibody (ACA), 15.3% Pm-SCL, 14.1% anti-topoisomerase I, 11.5% anti-RNA polymerase antibody (ARA) (Table 1). 34/78 patients (43.6%) reported clinical improvement in calcinosis related symptoms. Response was similar between different autoantibody groups with exception of patients with ARA, in which clinical improvement was reported in 88.9% of the cases (p< 0.005). 25.6% reported minor AE: skin pigmentation after 10 years of use (1 case), gastrointestinal intolerance (3 patients), elevated liver transaminases (1 case), and unspecified poor tolerance (9 patients). AE were more frequent in the group that did not report benefit (2 vs18). No additional serological abnormalities or autoimmune diseases was observed during treatment period. Different types of PPI were prescribed in 65% of the cohort and this was evenly distributed in the 2 outcome groups.

Conclusion: Within the largest reported series of SSc calcinosis treated with minocycline, our results suggest clinical improvement in almost half of the patients treated with acceptable tolerability. We observed that ACA and late-stage ARA positive patients both had troublesome calcinosis but ARA positive were more likely to respond than other subgroups. This observation suggests that calcinosis pattern may differ amongst autoantibody defined groups, perhaps reflecting distinct pathogenic mechanisms.  Overall, minocycline may be helpful in the management of calcinosis in patients with SSc. A future prospective trial, stratified by SSc autoantibodies, is required to confirm these findings.

References: 1) Roberson et al, Ann Rheum Dis. 2003;62:267-269.  2) Balin et al, Arch Dermatol. 2012;148:455-62

Abstract Minocycline Table 1

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/minocycline-for-refractory-calcinosis-in-systemic-sclerosis-a-single-centre-observational-cohort-study/