The efficacy of intravenous immunoglobulin for the treatment of pyoderma gangrenosum: A systematic review and meta‐analysis

Treatment of pyoderma gangrenosum (PG) is challenging. Research on intravenous immunoglobulin (IVIg) in PG is predominantly case reports; however, studies with larger cohorts have now been published since the last systemic review in 2018.1 We performed a systematic review on patients with pyoderma gangrenosum treated with IVIg using PRISMA guidelines searching MEDLINE, EMBASE and Cochrane databases. Papers were assessed for demographics, treatments, efficacy and adverse effects. Univariable meta-analysis was performed with binary logistic regression using SPSS (Version 28.0, IBM Corp, Armonk, NY, USA). Forty-five papers including 101 patients were identified; an increase from the 2018 systematic review which identified 49 patients.1 PG patient demographics, comorbidities and anatomical sites were similar to other studies on PG populations (Table 1). Notably, our review identified a higher proportion of patients with a haematological disorder than a United Kingdom nation-wide retrospective cohort study (19.0% vs 3.9%).2 >0.999 IVIg was not typically a first-line therapy, with systemic steroids (88.0%), cyclosporine (36.0%), mycophenolate (32.0%), infliximab (20.0%) and adalimumab (20.0%) trialled prior; consistent with the immunosuppressant agents recommended by expert guidelines.3 More patients received biologic therapies prior to IVIg than in the 2018 systematic review; 20% versus 14% trialled infliximab and/or adalimumab prior to IVIg.1 This rise reflects the greater availability of biologics. Most treatments, including biologics, in our review were continued alongside IVIG. IVIg was administered at a median (range) total dose of 2.0 g/kg (0.5–6.0 g/kg) over 4 days (2–7 days), with cycles repeated monthly (median 1, range 0–3 months). A series of 7 patients retained efficacy with a lower dose of 0.5 g/kg/day over 2–3 days—suggesting a lower dose may be effective while reducing the costs of IVIg.4 The number of days IVIg was spread over did not affect treatment outcomes or adverse effects. A response was noted a median of 4 weeks (IQR 1–8) following IVIg commencement. The large IQR of both the time to initial response (1–8 weeks) and treatment length (3–9.1 months) suggests that there is considerable variability between patients. Fifty-seven (57%) cases demonstrated complete or near-complete resolution of PG following IVIg commencement, and 25 (25%) demonstrated partial response (Figure 1). Eighteen (18%) cases reported no response. Four cases employed IVIg monotherapy, of whom all responded (2 partial response and 2 near-complete response).5, 6 Univariate analysis revealed that PG patients undergoing IVIg treatment with previous or concurrent corticosteroid use had a 2.85 (95%CI 1.01–8.08, p-value = 0.049) and 4.41 (95%CI 1.51–12.86, p-value = 0.007) higher odds of achieving partial or complete resolution, respectively. A history of pathergy also demonstrated higher odds of complete resolution (OR3.43, 95%CI 1.21–9.7, p-value = 0.02). In patients with pathergy, the pathogenic mechanisms may be distinct and particularly responsive to IVIg7, 8; however, further research is required. Ten instances of adverse effects were reported of which 3 necessitated treatment cessation—1 case of sepsis and 2 of aseptic meningitis. There were no mortalities attributed to IVIg. Although over half of patients responded well to IVIg, the data are likely impacted by publication bias. Our univariate analysis demonstrating higher odds of resolution with previous or concurrent steroids should be interpreted with caution as most patients (88%) received steroids. The majority of the literature on PG treatments is from low-level evidence, with only two published randomized trials: a trial on infliximab and the STOP GAP trial on prednisolone versus cyclosporine.3, 9 IVIg is effective and safe treatment for PG. It has a role for patients who are poor candidates for immunosuppression, such as patients with malignancies and those at risk of infections.10 The option of a PG treatment that is not immunosuppressive is significant due to its association with malignancies and other autoimmune conditions. No additional acknowledgements. There were no funding sources for this work. The authors declare no conflict of interest. Ethical approval is not required for this systematic review. The data that support the findings of this study are available from the corresponding author upon reasonable request.