Subcutaneous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy that causes weakness and sensory deficits over the course of at least two months. Intravenous immunoglobulin (IVIg) is considered a first-line treatment in CIDP, both as induction and maintenance treatment. Subcutaneous immunoglobulin (SCIg) may present a viable alternative, offering potential advantages such as ease of use, participant preference, improved health-related quality of life, and cost-effectiveness, provided it is shown to be effective and safe.

To assess the benefits and harms of subcutaneous immunoglobulin as induction and maintenance treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

We searched the Cochrane Neuromuscular Register, CENTRAL, MEDLINE, Embase, and two trials registries up to 21 July 2025. We also checked references, performed citation searching, and contacted study authors to identify additional studies.

We selected randomised controlled trials (RCTs) that compared SCIg with placebo or any other intervention in people with "probable" or "definite" CIDP, according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria.

We grouped participants based on treatment status (induction or maintenance treatment). Our primary outcome in the induction treatment group was improvement in disability (dichotomous), and our primary outcome in the maintenance treatment group was clinically significant deterioration in disability (dichotomous). Secondary outcomes included change in mean disability score, change in mean grip strength, and frequency of local and systemic adverse effects. For induction treatment, we were interested in measurements at six to 12 weeks (and also at 24 weeks for change in mean disability score), while for maintenance treatment, we were interested in measurements at 12 to 24 weeks. Two review authors independently reviewed the literature searches, extracted data, assessed risk of bias using the Cochrane risk of bias tool RoB 1, and assessed the certainty of the evidence with GRADE. We contacted study authors where appropriate. We synthesised results using random-effects meta-analysis where possible, reporting mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, each with its 95% confidence interval (CI).

Four RCTs with 360 randomised participants met our eligibility criteria. The mean age of participants was 55 (standard deviation (SD) 8.7) years, and 223 participants (62%) were men. Three studies (340 participants) had a parallel-group design and compared SCIg with placebo as maintenance treatment. One study (20 participants) had a cross-over design and compared SCIg with IVIg as induction treatment. The studies were conducted in different countries in North America, South America, and Europe, as well as Israel, Australia, and Japan. The study sites were neuromuscular clinics or general neurology departments. One study (172 participants) in the maintenance treatment group included a prestudy IVIg washout phase to determine IVIg dependency. It was the only study we rated at low risk of bias in all domains. Induction treatment We could not evaluate the difference between SCIg and IVIg as induction treatment in terms of rate of improvement in disability, change in grip strength, or frequency of local or systemic adverse effects, as these data were not available. SCIg compared with IVIg as induction treatment may result in little or no change in mean disability score within five weeks (MD 1.00% more improvement, 95% CI 20.94% more to 18.94% less; 1 study, 20 participants; low-certainty evidence). We found no studies comparing SCIg to placebo for inclusion in this review. Maintenance treatment SCIg maintenance treatment probably reduces the risk of clinically significant deterioration in disability within 12 to 24 weeks compared to placebo (RR 0.40, 95% CI 0.28 to 0.56; 3 studies, 333 participants; moderate-certainty evidence). SCIg probably improves change in mean grip strength compared to placebo (MD 6.46 kilopascals (kPa) higher, 95% CI 2.73 higher to 10.20 higher; 2 studies, 304 participants; moderate-certainty evidence), with the CI including a clinically significant increase (8.0 kPa). SCIg probably improves change in mean disability score compared to placebo (SMD 0.65 lower, 95% CI 1.03 lower to 0.27 lower; 3 studies, 333 participants; moderate-certainty evidence). SCIg compared with placebo is probably associated with a higher risk of local adverse effects (RR 3.39, 95% CI 1.97 to 5.82; 3 studies, 333 participants; moderate-certainty evidence), but we found no difference in the risk of systemic adverse effects (RR 0.94, 95% CI 0.69 to 1.27; 3 studies, 333 participants; moderate-certainty evidence). We found no studies comparing SCIg to other interventions for inclusion in this review.

There is a lack of evidence on SCIg as induction treatment compared with placebo. It is unclear whether SCIg is effective as induction treatment compared to IVIg. RCTs comparing SCIg with placebo or other induction treatments are needed to provide evidence on its potential benefits. SCIg maintenance treatment probably reduces deterioration in disability compared with placebo. SCIg probably improves mean grip strength and mean disability score compared with placebo, at the cost of a probable increase in the risk of local adverse effects and little to no difference in the risk of systemic adverse effects. Adverse effects were mostly local site reactions and were generally mild. We were unable to evaluate whether SCIg maintenance treatment is as beneficial as other maintenance treatments (such as IVIg). Future RCTs of this comparison should preferably enrol people with demonstrated active disease.