Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica

Abstract

Background:Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange. Data on the use of IA during pregnancy and breastfeeding are scarce.Methods:In this retrospective multicenter study, we analyzed the safety and efficacy of IA treatment in acute relapses during pregnancy or breastfeeding. The primary outcome parameter - change of acute relapse-related disability after IA - was assessed using Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON).Results:A total of 24 patients were analyzed, 23 with relapsing–remitting MS, and 1 with NMOSD. Twenty patients were treated with IA during pregnancy. Four patients received IA postnatally during the breastfeeding period. Treatment was started at a mean 22.5 [standard deviation (SD) 13.9] days after onset of relapse. Patients were treated with a series of 5.8 (mean, SD 0.7) IA treatments within 7–10 days. Sixteen patients received IA because of steroid-refractory relapse, eight were treated without preceding steroid pulse therapy. EDSS improved clinically relevant from 3.5 [median, interquartile range (IQR) 2] before IA to 2.5 (median, IQR 1.1) after IA, p < 0.001. In patients with ON, VA improved in four out of five patients. Altogether, in 83% of patients, a rapid and marked improvement of relapse-related symptoms was observed after IA with either a decrease of ⩾1 EDSS grade or improvement in VA ⩾20%. No clinically relevant side effect was reported in 138 IA treatments.Conclusions:Tryptophan-IA was found to be effective and well tolerated in MS/NMOSD relapses, both as an escalation option after insufficient response to steroid pulse therapy and as first-line relapse treatment during pregnancy and breastfeeding.

Therapeutic Apheresis in Acute Relapsing Multiple Sclerosis: Current Evidence and Unmet Needs—A Systematic Review

“…Additionally, every fourth woman with MS experiences a relapse during pregnancy, and nearly every third suffers from a relapse in the first three months after birth [74]. Although the amounts of IVMPS in breastmilk are low, breastfeeding should be avoided for several hours after a high maternal dose and might occasionally cause temporary loss of milk supply [75]. Moreover, especially within the first trimester of pregnancy, high doses of IVMPS bear serious risks (preterm birth, a lower bodyweight of the child, and/or facial/palatal cleft) [76,77].…”

“…Further, one retrospective study and several case reports suggest TPE and IA treatment for acute RRMS relapse during pregnancy and breastfeeding, considering them as rather a safe option [75,83,84]. In 2018, Hoffmann and colleagues conducted the largest retrospective study on this special cohort thus far, analyzing the use of tryptophan IA during pregnancy and breastfeeding in 24 patients.…”

“…In 83% of patients, a rapid and marked improvement of the TND was achieved, defined either as an EDSS decrease of ≥1.0 point or improvement in VA ≥20% at discharge. Moreover, no clinically relevant side effects were reported in connection with the 138 IA treatments [75].…”

“…In contrast to TPE, most coagulation factors remain unaffected by IA, except fibrinogen, especially in terms of tryptophan based IA [87]. However, no fibrinogen substitution was required in pregnancy IA studies [75]. Thus, reduced bleeding risk in the perinatal period and reduced thrombotic risk due to the reduction of antithrombin can be achieved with IA treatment compared to TPE [88].…”

Therapeutic plasma exchange in pregnancy: A literature review

“…Although evidence is limited to a few case reports for pregnant patients with Guillain-Barré syndrome; Myasthenia Gravis; Systemic Lupus Erythematosus; Multiple Sclerosis or Neuromyelitis Optica, TPE is stated as an accepted first or second line treatment in the non-pregnant population [1]. It is arguable that, if no alternative treatment possible, preconceptionally started TPE should be continued in pregnancy for these indications, and in case of deterioration of disease in pregnancy TPE may be taken into consideration [3,[57][58][59].…”