Potential Role for IVIG in Treating Systemic Sclerosis With Muscular, Digestive Manifestations

Intravenous immunoglobulin (IVIG) could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations of systemic sclerosis (SSc), though more research is necessary, according to a systematic review of studies published in Rheumatology International.¹

SSc is a systemic inflammatory and autoimmune disease, characterized by skin and visceral fibrosis. The physiopathology isn’t entirely understood, but it is believed that impaired immune response with the production of specific autoantibodies plays a significant role.¹

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Despite recent advances in treatment, SSc remains a severe disease that is associated with high morbidity and mortality. Treatment options remain limited; a recent advancement was the FDA granting orphan drug designation to belimumab, a B-lymphocyte stimulator-specific inhibitor, for the potential treatment of SSc.^1,2

The significant heterogeneity of SSc regarding its clinical manifestations, prognosis, severity, and response to treatment make it difficult to diagnose and subsequently treat. Typically, treatment is prescribed according to the domain involved, including immunosuppressive and antifibrotic therapies.³

Although not fully understood, IVIG could be useful in SSc by providing an immunomodulatory and antifibrotic effect. The investigators sought to analyze a series of clinical case reports published in recent years to determine whether IVIG is an efficacious alternative in SSc.¹

In total, 1242 studies were identified; after excluding duplicates and undergoing full-text reading, the investigators included 15 studies. Across these studies, 361 patients with SSc were included; 298 (82.5%) were women. Diffuse cutaneous SSc (dsSSc) was confirmed in 263 patients, and 295 received treatment with IVIG.¹

The clinical trial by Takehara et al. found improvements in modified Rodnan skin score (mRSS) after a second course of IVIG administration in the observational phase of their trial. However, there was no difference in joint range of motion found between IVIG and placebo.¹

Poelman et al. studied 30 patients receiving IVIG and described a significant improvement in mRSS at 6, 12, 18, and 24 months after treatment. Similarly, Agostini et al. found that the 24 patients who received IVIG treatment experienced a significant improvement in the mRSS at 6 and 12 months.¹

Other studies, conducted by Raja et al., Levy et al., and Inh et al. also found significant improvement in mRSS after IVIG treatment in small cohorts of patients. Another trial, conducted by Tandaipan et al., reported the effectiveness and safety of IVIG in 55 patients with SSc who received treatment, with an improvement of baseline mRSS.¹

Six studies evaluated the muscular and gastrointestinal domains each. Regarding the muscular domain, patients involved in the 6 studies generally reported improvements in muscle pain and weakness for patients treated with IVIG compared to those receiving placebo or receiving other drug treatments.¹

Moving to assessment of the gastrointestinal domain, there was a consensus of improvement when treated with IVIG. Sanges et al. found a significant improvement of gastrointestinal reflux disease and bowel symptoms in patients treated with IVIG. Several other cases were described, which all reported improvement in gastrointestinal areas.¹

Most of the adverse effects reported throughout the review were mild, with the most frequent being headache and abdominal symptoms such as pain, nausea, or vomiting. The safety profile was found to be akin to that reported in idiopathic inflammatory myopathy.¹

The investigators wrote that, based on the positive safety profile, IVIG “could be used in patients with malignancy, severe infections, or other situations in which other immunosuppressive treatments cannot be prescribed.”¹

Limitations of the review were discussed. Several factors could have influenced the results of the selected studies, including the heterogeneous study population, the different reasons for IVIG treatment across studies, and the variable dose or frequency of IVIG administration.¹

Additionally, IVIG treatment was prescribed for several different indications, and efficacy of the therapy could have been evaluated through different outcomes in those patients. Many of the students included a small number of patients, with no control group, which led the investigators to urge caution while interpreting the results.¹

References

1. Garrote-Corral S, Botello Corzo D, Loarce-Martos J, et al. Efficacy and safety of intravenous immunoglobulin therapy in systemic sclerosis: a systematic review. Rheumatol Int. 2024. doi:10.1007/s00296-024-05613-5

2. Antrim A. FDA grants Orphan Drug Designation to belimumab for systemic sclerosis treatment. Pharmacy Times. Published February 6, 2023. Accessed August 9, 2024. https://www.pharmacytimes.com/view/fda-grants-orphan-drug-designation-to-belimumab-for-systemic-sclerosis-treatment

3. Allanore Y, Simms R, Distler O, et al. Systemic sclerosis. Nat Rev Dis Primers. 2015;1:15002. doi:10.1038/nrdp.2015.2