IVIG may be worthwhile in treatment of refractory active diffuse scleroderma

Intravenous immunoglobulin may be an effective add-on therapy for patients with active diffuse cutaneous systemic sclerosis who are unresponsive to traditional immunosuppressive treatment, a single-center, observational study reports.

While intravenous immunoglobulin (IVIG) is commonly used to treat other autoimmune diseases, its effects on patients with systemic sclerosis is unclear, reported the authors led by Corrie L. Poelman and associates at Johns Hopkins University, Baltimore (J. Rheumatol. 2014 Nov. 29 [doi:10.3899/jrheum.140833]).

Their observational study involved 30 patients with refractory active diffuse cutaneous systemic sclerosis (dcSSc) who received treatment at the Johns Hopkins Scleroderma Center during 2004-2012.

The majority of patients (90%) had attempted other immunomodulatory or antifibrotic therapies without significant benefit.

Patients received IVIG 2 g/kg per month as part of routine clinical care. On average, patients completed 8.5 cycles of therapy along with concomitant therapy, which included mycophenolate mofetil (MMF, 70%), prednisolone (33.3%), cyclophosphamide (20%), methotrexate (10%), imatinib (3.3%), and hydroxychloroquine (3.3%).

Results showed a significant improvement in skin thickening over time, the researchers said.

The cohort’s mean baseline modified Rodnan skin score (mRSS) of 29.6 significantly decreased to 24.1 (n = 29; P = .0011) at 6 months, 22.5 (n = 25; P = .0001) at 12 months, 20.6 (n = 23; P= .0001) at 18 months, and 15.3 (n = 15; P < .0001) at 24 months.

Given the study’s retrospective nature, lack of a placebo control, and the frequent use of concomitant therapy, the researchers compared the changes in mRSS in the cohort with data from three large negative trials.

The comparison suggested that the improvement seen in their cohort “may be greater at 12 months than what would be expected by the natural history of the disease,” they said.

“In addition, the cohort treated with IVIG had a clinical improvement in mRSS that was similar to a group of patients treated with MMF who were typically deemed clinical responders, suggesting that addition of IVIG may stabilize previous refractory disease,” they added.

While the researchers did not see improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI) – a measure of activity and disease damage – patients’ assessments of disease severity significantly improved over time.

More than 70% discontinued IVIG because of improvement or stabilization as assessed by the treating physician, including one patient who developed an acute renal injury 15 months after discontinuing it because of improvement. Other discontinuations involved one who developed aseptic meningitis and stopped taking it because of severe side effects, one who stopped because of a transient ischemic attack, two who quit because of insurance coverage issues. One patient died of sudden cardiac arrest from a preexisting cardiomyopathy 16 months after initiating IVIG.

“IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies,” they concluded.

The study was supported by grants from the Scleroderma Research Foundation, he Catherine A. Keilty Memorial Fund for Scleroderma Research, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No disclosures were given.

Intravenous immunoglobulin may be an effective add-on therapy for patients with active diffuse cutaneous systemic sclerosis who are unresponsive to traditional immunosuppressive treatment, a single-center, observational study reports.

While intravenous immunoglobulin (IVIG) is commonly used to treat other autoimmune diseases, its effects on patients with systemic sclerosis is unclear, reported the authors led by Corrie L. Poelman and associates at Johns Hopkins University, Baltimore (J. Rheumatol. 2014 Nov. 29 [doi:10.3899/jrheum.140833]).

Their observational study involved 30 patients with refractory active diffuse cutaneous systemic sclerosis (dcSSc) who received treatment at the Johns Hopkins Scleroderma Center during 2004-2012.

The majority of patients (90%) had attempted other immunomodulatory or antifibrotic therapies without significant benefit.

Patients received IVIG 2 g/kg per month as part of routine clinical care. On average, patients completed 8.5 cycles of therapy along with concomitant therapy, which included mycophenolate mofetil (MMF, 70%), prednisolone (33.3%), cyclophosphamide (20%), methotrexate (10%), imatinib (3.3%), and hydroxychloroquine (3.3%).

Results showed a significant improvement in skin thickening over time, the researchers said.

The cohort’s mean baseline modified Rodnan skin score (mRSS) of 29.6 significantly decreased to 24.1 (n = 29; P = .0011) at 6 months, 22.5 (n = 25; P = .0001) at 12 months, 20.6 (n = 23; P= .0001) at 18 months, and 15.3 (n = 15; P < .0001) at 24 months.

Given the study’s retrospective nature, lack of a placebo control, and the frequent use of concomitant therapy, the researchers compared the changes in mRSS in the cohort with data from three large negative trials.

The comparison suggested that the improvement seen in their cohort “may be greater at 12 months than what would be expected by the natural history of the disease,” they said.

“In addition, the cohort treated with IVIG had a clinical improvement in mRSS that was similar to a group of patients treated with MMF who were typically deemed clinical responders, suggesting that addition of IVIG may stabilize previous refractory disease,” they added.

While the researchers did not see improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI) – a measure of activity and disease damage – patients’ assessments of disease severity significantly improved over time.

More than 70% discontinued IVIG because of improvement or stabilization as assessed by the treating physician, including one patient who developed an acute renal injury 15 months after discontinuing it because of improvement. Other discontinuations involved one who developed aseptic meningitis and stopped taking it because of severe side effects, one who stopped because of a transient ischemic attack, two who quit because of insurance coverage issues. One patient died of sudden cardiac arrest from a preexisting cardiomyopathy 16 months after initiating IVIG.

“IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies,” they concluded.

The study was supported by grants from the Scleroderma Research Foundation, he Catherine A. Keilty Memorial Fund for Scleroderma Research, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No disclosures were given.

Intravenous immunoglobulin may be an effective add-on therapy for patients with active diffuse cutaneous systemic sclerosis who are unresponsive to traditional immunosuppressive treatment, a single-center, observational study reports.

While intravenous immunoglobulin (IVIG) is commonly used to treat other autoimmune diseases, its effects on patients with systemic sclerosis is unclear, reported the authors led by Corrie L. Poelman and associates at Johns Hopkins University, Baltimore (J. Rheumatol. 2014 Nov. 29 [doi:10.3899/jrheum.140833]).

Their observational study involved 30 patients with refractory active diffuse cutaneous systemic sclerosis (dcSSc) who received treatment at the Johns Hopkins Scleroderma Center during 2004-2012.

The majority of patients (90%) had attempted other immunomodulatory or antifibrotic therapies without significant benefit.

Patients received IVIG 2 g/kg per month as part of routine clinical care. On average, patients completed 8.5 cycles of therapy along with concomitant therapy, which included mycophenolate mofetil (MMF, 70%), prednisolone (33.3%), cyclophosphamide (20%), methotrexate (10%), imatinib (3.3%), and hydroxychloroquine (3.3%).

Results showed a significant improvement in skin thickening over time, the researchers said.

The cohort’s mean baseline modified Rodnan skin score (mRSS) of 29.6 significantly decreased to 24.1 (n = 29; P = .0011) at 6 months, 22.5 (n = 25; P = .0001) at 12 months, 20.6 (n = 23; P= .0001) at 18 months, and 15.3 (n = 15; P < .0001) at 24 months.

Given the study’s retrospective nature, lack of a placebo control, and the frequent use of concomitant therapy, the researchers compared the changes in mRSS in the cohort with data from three large negative trials.

The comparison suggested that the improvement seen in their cohort “may be greater at 12 months than what would be expected by the natural history of the disease,” they said.

“In addition, the cohort treated with IVIG had a clinical improvement in mRSS that was similar to a group of patients treated with MMF who were typically deemed clinical responders, suggesting that addition of IVIG may stabilize previous refractory disease,” they added.

While the researchers did not see improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI) – a measure of activity and disease damage – patients’ assessments of disease severity significantly improved over time.

More than 70% discontinued IVIG because of improvement or stabilization as assessed by the treating physician, including one patient who developed an acute renal injury 15 months after discontinuing it because of improvement. Other discontinuations involved one who developed aseptic meningitis and stopped taking it because of severe side effects, one who stopped because of a transient ischemic attack, two who quit because of insurance coverage issues. One patient died of sudden cardiac arrest from a preexisting cardiomyopathy 16 months after initiating IVIG.

“IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies,” they concluded.

The study was supported by grants from the Scleroderma Research Foundation, he Catherine A. Keilty Memorial Fund for Scleroderma Research, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No disclosures were given.