Table 1.
Recommendations on the application, monitoring, and important risks of preventive immunotherapies in NMOSD1,2
| Drug | Application | Full onset of action | Common side effects | Risk of infections | Other important risks | Blood monitoring | Additional suggested monitoring |
|---|---|---|---|---|---|---|---|
| Azathioprine | Oral, daily, 2.5–3.0 mg/kg body weight | After 6–12 months | Hematological abnormalities (lymphocytopenia, pancytopenia), elevation of liver enzymes, gastrointestinal side effects | Upper respiratory tract and urinary tract infections, opportunistic infections | Drug-induced fever, several drug interactions (including allopurinol, anti-viral and anti-coagulatory drugs), photosensitization (skin), increased cancer risk with duration of treatment (> 10 years) | BCC and differential WBCC, liver enzymes | Regular screening for cancer (by dermatologist, gynecologist) |
| Mycophenolate mofetil | Oral, daily, 1000–2000 mg | After 8–12 weeks | Hematological abnormalities (anemia), elevation in liver enzymes, gastrointestinal side effects | Upper respiratory tract and urinary tract infections, opportunistic infections | Increased cancer risk, teratogenic and embryotoxic effects | BCC and differential WBCC, liver enzymes | Regular screening for cancer (by dermatologist, gynecologist) |
| Glucocorticoids |
For attack: i. v., 1x/day, 1000–2000 mg, over 3–5 days For taper: oral, 1x/day, starting with 1 mg/kg/day or 20–30 mg/day and then tapered to 10–15 mg within 2–3 weeks; For long-term use: oral, 1x/day, individual dosing (ideally ≤ 7.5 mg/day) |
Immediate effects | Hematological abnormalities (lymphopenia), elevation in liver enzymes | Increased risk for infections, including opportunistic infections (e.g., PJP, particularly if administered with other IS) | Diabetes, arterial hypertension, osteoporosis, cataract, adrenal insufficiency, Cushing’s syndrome | BCC and differential WBCC, liver enzymes, electrolytes, blood glucose | Use of glucocorticoids in combination with proton pump inhibition and thrombosis prophylaxis Monitoring of blood pressure; with long-term use: bone densitometry, eye examination, cardiovascular check-ups |
| Rituximab | i. v., with premedication (glucocorticoids, antiphlogistics, antihistamines); usually initially 1000 mg at day 1 and day 14, followed by 500–1000 mg every 6 months | B-cell depletion within 4 weeks, full onset of action after 8–12 weeks | Nausea, exanthema, headache | Upper respiratory tract and urinary tract infections, hepatitis B reactivation, opportunistic infections (including PML), no PML in NMOSD reported so far | Infusion-related pseudo-allergic reactions (due to cell lysis), leucopenia, neutropenia and LON, hypogammaglobulinemia | Differential WBCC, serum immunoglobulins, CD19/20-positive B-cell count | Monitoring for infusion-related (allergic) reactions |
| Inebilizumab | i. v., with premedication (glucocorticoids, antiphlogistics, antihistamines); initially 300 mg at day 1 and day 14, followed by 300 mg every 6 months | B-cell depletion within 2 weeks, full onset of action after 6–8 weeks | Arthralgias, back pain | Upper respiratory tract and urinary tract infections, opportunistic infections (including PML) | Infusion-related pseudo-allergic reactions (due to cell lysis), lymphopenia, neutropenia and LON, hypogammaglobulinemia | Differential WBCC, serum immunoglobulins, CD19/20-positive B-cells count | Monitoring for infusion-related (allergic) reactions |
| Eculizumab | i. v., 900 mg 1x/week weeks 0–3, 1200 mg 1x/week week 4, thereafter 1200 mg every 2 weeks | Immediate within 1–2 weeks | Headaches, upper respiratory tract infections | Meningococcal infection and infections with other encapsulated bacteria | Anemia, leukopenia, fungal infections, infusion-related (allergic) reactions | BCC and differential WBCC | Patient teaching and close monitoring for meningococcal infection (exclusion before each infusion) |
| Ravulizumab | i. v., weight-based2, loading dose of 2400–3000 mg on days 1 and 15 followed by 3000–3600 mg once every 8 weeks | Immediate within 1–2 weeks | Headaches, upper respiratory tract infections | Meningococcal infection and infections with other encapsulated bacteria | Anemia, leukopenia, fungal infections, infusion-related (allergic) reactions | BCC and differential WBCC | Patient teaching and close monitoring for meningococcal infection (exclusion before each infusion) |
| Tocilizumab | i. v., 6–8 mg/kg body weight, every 4–6 weeks* | After 12 to 24 weeks | Injection-related reactions, headache | Upper respiratory tract and urinary tract infections | Neutropenia, thrombocytopenia, elevation in liver enzymes, flare-up of chronic diverticulitis with potential gastrointestinal perforations, elevations in cholesterol or triglycerides, infusion-related (allergic) reactions | BCC and differential WBCC, liver enzymes, lipids | Clinical monitoring for infections due to suppression of CRP production in the context of infections |
| Satralizumab | s. c., 120 mg at weeks 0, 2, and 4, followed by every 4 weeks | After 12 to 24 weeks | Injection-related reactions, headache, arthralgia, | Mild to moderate infections, no opportunistic infections so far reported | Neutropenia, thrombocytopenia, elevation in liver enzymes, elevations in cholesterol or triglycerides, decrease in C3, C4 and fibrinogen | BCC and differential WBCC, liver enzymes, lipids | Clinical monitoring for infections due to suppression of CRP production in the context of infections |
BCC blood cell count, CRP C-reactive protein, IS immunosuppressive therapies, i. v. intravenously, LON late-onset neutropenia, PJP pneumocystis jirovecii pneumonia, PML progressive multifocal leukoencephalopathy, s. c. subcutaneously, WBCC white blood cell count
1These aggregated recommendations do not include all potential side effects and do not replace the specific product information for each drug; 2for details see product information
*switch to s. c. application possible