Background/Purpose: A subset of patients with active diffuse cutaneous scleroderma has refractory disease despite traditional immunosuppressive therapy. In this retrospective observational study, we investigated whether intravenous immunoglobulin (IVIG) improved skin thickening in patients with refractory disease compared to data from historical controls.

Methods: Scleroderma patients receiving IVIG to treat diffuse cutaneous disease that was active despite other therapy were identified from the Johns Hopkins Scleroderma Center database and medical record review. The mean modified Rodnan skin score (mRSS) at baseline was compared to the mRSS at 6, 12, 18 and 24 months post-IVIG initiation by paired t-test. Clinical “responders” at 6 and 12 months were defined by a mRSS decline of at least 5 points based on previously published data examining the minimal clinically important difference. Potential predictors of response were examined by Student’s t-test, Fisher’s exact test, and logistic regression analysis where appropriate. Changes in mRSS at 6 and 12 months were also compared to data from historical controls of 3 large, negative, multicenter, randomized clinical trials of other medications (D-penicillamine (D-pen), Recombinant Human Relaxin (Relaxin), and Oral Bovine Type I Collagen (Collagen) trials) using the Student’s t-test. 

Results: Out of 66 patients who received IVIG between 2004-2012, 30 were treated for active diffuse cutaneous disease and were included for analysis. The study population had a mean age of 42.7 ± 14.4 years at scleroderma onset, were predominantly female (80%) and white (86.7%), and had a mean scleroderma disease duration of 3.9 ± 5.9 years at initiation of IVIG. Patients received an average of 8.3 ± 4.6 monthly IVIG cycles. Concomitant medication use included methotrexate (10%), mycophenolate (70%), cyclophosphamide (20%), and corticosteroids (33.3%). The mean baseline mRSS was 29.6 ± 7.2, and this significantly decreased to 24.6 ± 9.4 (N=28; p=0.0017) at 6 months, 22.0 ± 10.1 (N=26; p<0.0001) at 12 months, 21.0 ± 11.5 (N=23; p=0.0002) at 18 months and 15.3 ± 6.4 (N=15; p<0.0001) at 24 months. 15/28 patients and 16/26 patients were “responders” to IVIG therapy at 6 and 12 months, respectively. None of the examined parameters (age, disease duration at IVIG initiation, duration of IVIG therapy, autoantibody status, and concomitant immunosuppressive therapy) were associated with responder status at 6 or 12 months.

The mean baseline mRSS in the IVIG group (29.6 ± 7.2) was similar to that of the Relaxin trial (27.3 ± 6.9, p=0.09), but was significantly higher than that observed in the D-pen (21.0 ± 8.0, p<0.0001) and Collagen (26.1 ± 7.8, p=0.023) trials.  At 6 months, the mean change in mRSS was not significantly different in the IVIG group (-5.3 ± 8.0) compared to the Relaxin trial (-4.8 ± 6.99, p=0.75); however, at 12 months the mean change in mRSS was significantly better in the IVIG group (-7.9 ± 8.1) than in the D-pen (-2.5 ± 8.6, p=0.0044) and Collagen (-3.4 ± 7.1, p=0.0047) groups.

Conclusion: This study suggests that IVIG may be an effective therapy for active diffuse cutaneous disease in patients who have been refractory to other immunosuppressive therapies.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/intravenous-immunoglobulin-may-be-an-effective-therapy-in-scleroderma-patients-with-refractory-active-diffuse-cutaneous-disease/