IVIG reduces skin thickening, gastrointestinal symptoms in systemic sclerosis
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Key takeaways:
- IVIG had favorable effects on skin thickening, muscle and joint pain, and gastrointestinal symptoms of systemic sclerosis.
- Larger double-blind trials are needed, but “may be difficult to conduct.”
Intravenous immunoglobulin treatment may benefit skin, musculoskeletal and gastrointestinal manifestations of systemic sclerosis, with low risks for adverse events, according to data published in Seminars in Arthritis and Rheumatism.
“The use of IVIG in SSc was first reported in the early 2000s, when three patients showed marked skin thickness reduction after a 6-monthly course of IVIG,” Sasza Koczanowski, BBiomed, of the University of Melbourne, and colleagues wrote. “Subsequently, multiple studies have investigated the role of IVIG in SSc treatment, particularly in patients refractory to other immunomodulatory treatments. The results of these studies show variable effect. Whilst some studies have systematically examined the use of IVIG for a single organ system in SSc, none have comprehensively done so across multiple organ systems.”
To assess the current data on IVIG use across SSc manifestations, Koczanowski and colleagues conducted a systematic literature review. The researchers examined records from the Medline, Embase, Cochrane, Web of Science and Scopus databases from 2003 through April 15, 2024. The final analysis included 12 studies — one randomized controlled trial, two pilot studies, one open-label study, seven retrospective studies and one case-control study — representing a total of 266 adults with SSc.
The researchers assessed the quantitative impact of IVIG on outcomes in skin, respiratory function and musculoskeletal and gastrointestinal organ systems, as well as physician- and patient-reported clinical improvement and corticosteroid sparing benefit. However, they noted that the included studies were “small and of poor quality,” with the literature on IVIG in SSc comprising “mostly non-randomized studies with small sample sizes at high risk of bias.”
According to the researchers, the analysis demonstrated that IVIG treatment was associated with reduced skin thickening, muscle and joint pain, and gastrointestinal symptoms. However, the treatment appeared “less beneficial” in respiratory disease but was linked to stabilized pulmonary function tests and radiological features.
In addition, across three studies examining steroid sparing, all showed “a significant reduction in corticosteroid dose” with IVIG treatment, the researchers wrote. All three studies demonstrated improvements to scores on the patient-reported Health Assessment Questionnaire, and one study showed physician-reported improvements in clinical outcomes and time to relapse.
“This study provides evidence to support the use of IVIG as an effective steroid-sparing agent in the management of cutaneous, musculoskeletal, and [gastrointestinal] manifestations of SSc, particularly as an adjunct or additional therapy for refractory disease,” Koczanowski and colleagues wrote. “When administered according to recommended guidelines, the risk of serious adverse events is low, highlighting IVIG as a potentially attractive option for SSc treatment.
“However, its high cost and limited availability may act as a barrier to more widespread utilization,” they added. “Included studies were small and of poor quality, and whilst large double-blind [randomized controlled trials] are desirable to confirm these effects and inform the development of consensus guidelines for IVIG use, given the rarity and heterogeneity of SSc, such studies may be difficult to conduct.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
The authors of this analysis found 12 studies that were worthy of review, and only one had a randomized control group. This and other papers suggest IVIG appears to help the skin, the musculoskeletal system (including myositis) and the gastrointestinal tract in SSc.
However, the condition of scleroderma is not specifically listed in the insurance plans that I have reviewed regarding IVIG. It is listed neither as an accepted diagnosis nor as an excluded diagnosis. It appears approval may be on a case-by-case basis.
Studies have demonstrated that IVIG effectively prevents skin inflammation and fibrosis by reducing immune cell infiltration, proinflammatory cytokine expression — including IL-1β,TNF alpha and IL-6 — and reducing markers associated with fibrosis — including alpha-smooth muscle actin, a key marker for the differentiation of myofibroblasts, as well as collagen and fibronectin.
Additionally, IVIG prevented alterations in splenic cell homeostasis induced by hypochlorous acid — an experimental way to induce oxidative stress or inflammation. However, when administered after the onset of symptoms, IVIG showed only partial or mixed effects on existing inflammation and fibrosis.
This is a promising development that can be used in patients with rapidly progressive scleroderma that fails to respond to conventional therapies. Aggressive treatment — coupled with aggressive prior authorization — will be needed for this therapy.
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