Background/Purpose: Juvenile localized scleroderma (jLS) is an autoimmune disease commonly associated with damage. Damage includes dyspigmentation, tissue atrophy, arthropathy, hemiatrophy, vision loss, and seizures. To limit damage severity, methotrexate (MTX), with or without glucocorticoids (GC), is recommended to treat patients with active disease. This regimen is effective in ~70% of patients. Evidence on how to treat non-responders is limited, with some patients having persistently active disease for decades.

Many studies have identified T cells and their associated cytokines in patients with active disease, which suggests abatacept (ABA), a selective T cell co-stimulatory signal inhibitor, could be an effective treatment. A good response to ABA has been reported in small case series of adult onset patients who failed MTX. We report our experience using ABA to treat refractory jLS patients.

Methods: This was a multi-center retrospective cohort study of jLS patients that initiated ABA treatment prior to 7/1/18. Inclusion criteria included diagnosis of jLS, with onset < 16 years. Charts were reviewed to extract demographics, disease characteristics, medication history, and reasons for ABA use. Data was collected at start of ABA (baseline), and at 6 month intervals up to 24 months, or ABA discontinuation, whichever was sooner. Descriptive statistics analysis was performed.

Results: 18 patients were evaluated, median age 13.4 years, disease duration 3.7 years. Most had linear scleroderma (Table 1). All had been previously treated with glucocorticoids, and MTX (17) and/or mycophenolate mofetil (MMF, 16), each for a median duration of >1 year (Table 1).  Reasons for ABA use included persistent disease or flare (14, 78%), intolerance of other medications (5, 28%), and GC dependence (4, 22%). ABA was dosed per JIA recommendations, with 16 treated intravenously. All patients concurrently received other treatment: MTX (12), MMF (10), hydroxychloroquine (1), and GC (14).

 Median scores for physician global assessment of disease activity and skin activity measures all declined by 12 months, and then stabilized or further declined (Figure 1). At 12 months, 17 (94%) patients were rated as improved in activity status compared to baseline, and 9 of the 12 patients with joint involvement were rated as improved. At 24 months, 9 of 11 patients (82%) on ABA were rated as improved, and 7 with joint involvement were all rated as improved.  During ABA treatment, 10 patients were able to discontinue GC (71% of patients on GC, Figure 2).  

Eight patients had an adverse event (AE); 7 were on concomittant medications. AE included fatigue, moodiness, behavioral change, and one infection (upper respiratory infection). No laboratory abnormalities were attributed to ABA. Two patients discontinued ABA because of mood and/or behavioral issues.

Conclusion: ABA was found to be a safe and effective treatment for jLS patients who previously failed MTX and/or MMF. There were no serious AE. Patients treated with ABA had a decrease in both skin and joint activity. Seventy percent of GC treated patients were able to discontinue GC. Prospective studies should be done to further evaluate ABA’s efficacy, potentially as stand-alone therapy and/or in combination with DMARDs.

Table: Characteristics of the 18 jLS patients who were treated with abatacept. All of the patients received other jLS treatment prior to being treated with abatacept: 17 were treated with methotrexate, 16 with mycophenolate mofetil, and 17 with glucocorticoids. The median duration of these treatments are listed. The median duration of abatacept treatment for the patients during their study follow-up is shown. ABA:abatacept; ANA: anti-nuclear antibody; CK: creatine kinase; GC: glucocorticoid; IQR: interquartile range; MMF: mycophenolate mofetil; MTX: methotrexate; no: number.

Figure 1: Change in skin activity and physician global assessment scores on ABA. Skin Activity measures were mLoSSI and LSCAM. Physician global assessment were of activity (PGA-A) and damage (PGA-D). mLoSSI sums 3*disease extension + erythema + skin thickening across affected sites, LSCAM sums same variables without weighting disease extension, and also includes scoring for violaceous color, waxy white/ yellow, and tactile warmth features. Number of patients that were scored at each time point: 18 at 0, 6 months; 17 at 12 months; 14 at 18 months, 11 at 24 months. Reasons for missing visits were: discontinuation of abatacept prior to 24 months (because of adverse event [2], pregnancy [1], persistent disease activity [1]), end of study collection period (2), and patient moved out of state (1). LSCAM: Localized scleroderma cutaneous activity measure mLoSSI: modified localized scleroderma severity index PGA-A = Physician global assessment of disease activity PGA-D = Physician global assessment of disease damage

Figure 2 : Concomitant glucocorticoid treatment with Abatacept treatment The percent of patients on glucocorticoid treatment at each study visit is shown. Overall, 14 patients were treated with glucocorticoids during the study, 13 begun at baseline and an additional 1 by 6 month visit. Percentages shown are based upon total number of patients at each study visit; 18 patients at 0 and 6 month, 17 at 12 month, 14 at 18 month, and 11 at 24 month visit. Ten patients discontinued glucocorticoids by their last study visit.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abatacept-treatment-reduces-cutaneous-and-joint-activity-in-juvenile-localized-scleroderma-2/