Table 1 Efficacy and safety of antiāIL-6 therapies on neuropathic pain in patients with NMOSD
From: Interleukin-6: evolving role in the management of neuropathic pain in neuroimmunological disorders
AntiāIL-6 therapy | ||||||
|---|---|---|---|---|---|---|
Author, year (study design) | Clinical characteristics of patients | Prior/concomitant medications | Dose, frequency of administration, and duration of treatment | Efficacy (NRS/VAS) | Safety | |
NRS/VAS at baseline | NRS/VAS at the end of treatment/last follow-up | |||||
Araki et al., 2013 (CR) [20] | A 36-year-old female patient with NMO | Combination of PSL and AZA | 8 mg/kg i.v. every month for 6 months | NRS: 4 | NRS: 0 | Decline in SBP, lymphocytopenia, viral enteritis, and upper respiratory infection of unknown origin |
Araki et al., 2014 (pilot study) [21] | Seven (six female and one male) patients with refractory AQP4-Ab-seropositive NMO or NMOSD | PSL or AZA alone or PSL in combination with AZA, CyA, or tacrolimus | 8 mg/kg every month for 1 year | NRS, mean Ā± SEM: 3.0 Ā± 1.5 | NRS at 6 months, mean Ā± SEM: 1.3 Ā± 1.3 NRS at 12 months, mean Ā± SEM: 0.9 Ā± 1.2 | Upper respiratory infection (n = 2), acute enterocolitis (n = 2), acute pyelonephritis (n = 1), leukocytopenia, and/or lymphocytopenia (n = 3), anemia (n = 2), and a slight decline in SBP (n = 1) |
Ringelstein et al., 2015 (ROS) [22] | Eight female patients with highly active AQP4-Ab-seropositive NMO (n = 6) or NMOSD (n = 2) | Immunomodulatory or immunosuppressant therapy (e.g., rituximab, interferon beta-1Ī², AZA) | 6ā8 mg/kg at a 4- to 6-week interval followed up to 10ā51 months | NRS, median ((IQR): 6.5 (5.0ā7.0) | NRS, median (IQR): 2.5 (0.3ā4.5) (p = 0.02) 7/8 patients had less pain at the last follow-up, with two of them completely pain free | Mild post infusion nausea (n = 1), transient gastritis (n = 1), transient diarrhea (n = 1), headache (n = 1), fatigue (n = 2), recurrent urinary tract infections (n = 3), deep venous thrombosis (n = 1), transient mild liver enzyme increase (n = 3), recurrent CRP elevation (n = 1), leukopenia or neutropenia (n = 2) and elevation of cholesterol levels (n = 6) |
Araki, 2019 (CS) [23] | 19 patients with refractory NMOSD | Corticosteroids and/or immunosuppressants | Dose not specified; monthly infusion up to 6 years and 8 months | NRS, mean Ā± SD: 3.2 Ā± 2.2 | NRS at 1 year after treatment: 1.7 Ā± 2.6 (p < 0.001) In one patient with comorbid SLE, severe neuropathic pain disappeared | Not reported |
Yamamura et al., 2019 (CT) [24] | 83 patients with AQP4-Ab- seropositive or AQP4-Ab- seronegative NMOSD: satralizumab, 41; placebo, 42 | Oral glucocorticoids, AZA, MMF, AZA + glucocorticoids, and MMF+oral glucocorticoids | 120 mg s.c. at weeks 0, 2, and 4 and every 4 weeks during the double-blind perioda | VAS (mean Ā± SD Satralizumab group: 27.6 Ā± 28.2 Placebo group: 34.6 Ā± 26.1 | The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, ā 8.44 to 16.61, p = 0.52) | Satralizumab vs placebo (%): Infection (68% vs 62%), IRR (12% vs 5%), neoplasmb (7% vs 7%), and serious infection (5% vs 7%) |
Traboulsee et al, 2020 (CT) [25] | 95 patients with AQP4-Ab- seropositive or AQP4-Ab-seronegative NMOSD: satralizumab,63; placebo, 32 | Previous: B-cell depleting therapy and immunosuppressants. Analgesics were permitted during satralizumab therapy | 120 mg s.c. at weeks 0, 2, and 4 and every 4 weeks thereafter in the double-blind period (maximal duration of 1.5 years after the random assignment of the last patient enrolled) | VAS (mean Ā± SD) Satralizumab group: 31.7 Ā± 28.9 Placebo group: 27.6 Ā± 30.8 | The adjusted mean of the VAS pain score change from baseline did not differ significantly between the two groups (between-group difference in mean score change 3.21 (95% CI, ā 5.09 to 11.52; p = 0.44). | Satralizumab vs placebo (%): Infections (54% vs 44%), IRR (13% vs 16%), and serious infections (10% vs 9%) |