Evaluation of Plasmapheresis vs Immunoglobulin as First Treatment After Ineffective Systemic Corticosteroid Therapy for Patients With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

ImportanceStevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse reactions, and patients with SJS/TEN frequently require intensive care. However, there is limited evidence on the clinical outcomes of immunomodulating therapy, including plasmapheresis and intravenous immunoglobulin (IVIG) in patients with SJS/TEN.ObjectiveTo compare clinical outcomes of patients with SJS/TEN who were treated with plasmapheresis first vs IVIG first after ineffective systemic corticosteroid therapy.Design, Setting, and ParticipantsThis retrospective cohort study used data from a national administrative claims database in Japan that included more than 1200 hospitals and was conducted from July 2010 to March 2019. Inpatients with SJS/TEN who received plasmapheresis and/or IVIG therapy after initiation of at least 1000 mg/d of methylprednisolone equivalent systemic corticosteroid therapy within 3 days of hospitalization were included. Data were analyzed from October 2020 to May 2021.ExposuresPatients who received IVIG or plasmapheresis therapy within 5 days after initiation of systemic corticosteroid therapy were included in the IVIG- and plasmapheresis-first groups, respectively.Main Outcomes and MeasuresIn-hospital mortality, length of hospital stay, and medical costs.ResultsOf 1215 patients with SJS/TEN who had received at least 1000 mg/d of methylprednisolone equivalent within 3 days of hospitalization, 53 and 213 patients (mean [SD] age, 56.7 [20.2] years; 152 [57.1%] women) were included in the plasmapheresis- and IVIG-first groups, respectively. Propensity-score overlap weighting showed no significant difference in inpatient mortality rates between the plasmapheresis- and IVIG-first groups (18.3% vs 19.5%; odds ratio, 0.93; 95% CI, 0.38–2.23; P = .86). Compared with the IVIG-first group, the plasmapheresis-first group had a longer hospital stay (45.3 vs 32.8 days; difference, 12.5 days; 95% CI, 0.4–24.5 d; P = .04) and higher medical costs (US $34 262 vs $23 054; difference, US $11 207; 95% CI, $2789–$19 626; P = .009).Conclusions and RelevanceThis nationwide retrospective cohort study found no significant benefit to administering plasmapheresis therapy first instead of IVIG first after ineffective systemic corticosteroid treatment in patients with SJS/TEN. However, medical costs and length of hospital stay were greater for the plasmapheresis-first group.

The Consideration of Cyclosporine in the Treatment of Stevens-Johnson Syndrome—Reply

“…Similarly, the administration of tumor necrosis factor α as an adjunct therapy being equally effective in patients with SJS/TEN has also been reported, despite the small sample size of the report compared with studies on cyclosporine . However, our study did not consider these immunomodulating agents as covariates . The rationale behind this was that the effectiveness of these drugs was not widely known during the study period (especially in the early 2010s).…”

“…2,3 However, our study did not consider these immunomodulating agents as covariates. 4 The rationale behind this was that the effectiveness of these drugs was not widely known during the study period (especially in the early 2010s). This was owing to insufficient evidence at that time, and consequently, these drugs have not been covered by Japanese medical insurance for SJS/TEN.…”

The Consideration of Cyclosporine in the Treatment of Stevens-Johnson Syndrome

“…To the Editor We recently read the work of Miyamoto and colleagues regarding the use of plasmapheresis vs intravenous immunoglobulin (IVIG) therapy as the initial treatment for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The authors conducted a trial to assess the benefits of these therapies, acknowledging the lack of guidelines for treating these rare disorders. The study noted that systemic steroids, plasmapheresis, and immunoglobulins were among the most used treatment options.…”

“…Another study in the meta-analysis reported a decrease in mortality from a 2.75 SCORTEN-predicted mortality rate to no reported mortality . The study by Miyamoto and colleagues also mentioned the benefits of IVIG in terms of decreased length of stay and hospitalization costs. It is important to mention a meta-analysis by Chen et al that showed a significantly reduced mean hospital stay from 23.9 days to 17.3 days when using a 3- to 10-day course of cyclosporine compared with 3 to 7 days of high-dose IVIG therapy .…”

“…It is important to mention a meta-analysis by Chen et al that showed a significantly reduced mean hospital stay from 23.9 days to 17.3 days when using a 3- to 10-day course of cyclosporine compared with 3 to 7 days of high-dose IVIG therapy . Miyamoto and colleagues finally mention costs as a possible benefit of treatment with IVIG; however, the administration of cyclosporine has been shown to greatly reduce costs, length of stay, and the risk of infections compared with IVIG, systemic steroids only, or plasmapheresis treatment . The purpose of this comment is to bring awareness of cyclosporine as a treatment option and to consider it as a primary treatment for SJS and/or TEN.…”