Table 5.
Tolerability, safety, and monitoring issues of DMTs for MS
| DMT | Common AEs | Safety issues | Contraindications |
|---|---|---|---|
| IFN beta-1b (Betaseron/Extavia) [134] | Injection site reaction, lymphopenia, flu-like symptoms, myalgia, leukopenia (asymptomatic), neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, asthenia, depression, hematologic abnormalities, arthralgia | Hepatic injury, anaphylaxis, depression (and suicidal ideation), injection site necrosis, congestive heart failure, leukopenia thrombotic microangiopathy, flu-like symptom complex, seizures, autoimmune disorders, decreased peripheral blood counts | Pregnancy (increased risk of spontaneous abortion) and breastfeeding Hypersensitivity reactions to active ingredient or formulation excipients |
| IFN beta-1a (Avonex) [135] | |||
| IFN beta-1a (Rebif) [136] | |||
| Peginterferon beta-1a (Plegridy) [137] | |||
| Glatiramer acetate (Copaxone) [138] | Injection site reactions, postinjection reaction (vasodilatation, rash, dyspnea, chest pain within minutes) | Cutaneous necrosis | Use during pregnancy only if clearly needed Hypersensitivity reactions to active ingredient or formulation excipients |
| Dimethyl fumarate (Tecfidera) [67, 68] | Flushing, abdominal pain, diarrhea, nausea (usually subsides within 3 months) [187] | Anaphylaxis and angioedema, PML, lymphopenia | Hypersensitivity reactions to active ingredient or formulation excipients |
| Teriflunomide (Aubagio) [72–74] | Headache, diarrhea, nausea, alopecia, increased alanine aminotransferase | Hepatic injury, teratogenicity (requires accelerated elimination procedure), bone marrow effects, potential immunosuppression, infection, peripheral neuropathy, skin AEs [including Stevens–Johnson syndrome or toxic epidermal necrolysis (Lyell’s syndrome)], increased blood pressure, respiratory effects (interstitial lung disease), pancreatitis, thrombocytopenia | Severe hepatic impairment Pregnancy and breast feeding Severe immunodeficiency Significantly impaired bone marrow function Severe active infection Severe renal impairment undergoing dialysis Hypoproteinemia (due to high plasma protein binding) Current leflunomide treatment Hypersensitivity reactions to active ingredient, leflunomide, or formulation excipients |
| Fingolimod (Gilenya) [12, 13] | Headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, infection, back pain, abdominal pain, pain in extremity | Asystole and sudden death, infections (including herpes simplex virus and cryptococcal infections), PML, macular edema, posterior reversible encephalopathy syndrome, respiratory effects, hepatic injury, teratogenicity, increased blood pressure, basal cell carcinoma | Recent myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or class III/IV heart failure History of Mobitz type II second- or third-degree AV block or sick sinus syndrome, unless patient has a pacemaker Baseline QTc interval ≥500 ms Known immunodeficiency syndrome Active infection Treatment with Class IA or Class III anti-arrhythmic treatment Active malignancy Severe liver impairment Hypersensitivity reactions to active ingredient or formulation excipients |
| Daclizumab-beta (Zinbryta) [81, 82]a | Nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, bronchitis, eczema and lymphadenopathy, depression, pharyngitis, increased alanine aminotransferase | Hepatic injury (including autoimmune hepatitis), other immune-mediated disorders (skin reactions, lymphadenopathy, noninfectious colitis), infections, and depression | Hypersensitivity reactions to active ingredient or formulation excipients Preexisting hepatic disease or hepatic impairment, including ALT or AST ≥2 times the ULN History of autoimmune hepatitis or other autoimmune condition involving the liver |
| Alemtuzumab (Lemtrada) [100, 141, 188–192] | Rash, headache, pyrexia, nasopharyngitis, nausea, vomiting, infection (urinary tract, upper respiratory tract, viral including herpes, fungal), fatigue, insomnia, urticaria, pruritus, thyroid gland disorders, arthralgia, pain in extremity, back pain, oropharyngeal pain, abdominal pain, diarrhea, sinusitis, paresthesia, dizziness, flushing | Infusion-associated reactions and anaphylaxis (including bradycardia), thyroid disorders and other autoimmune cytopenias, glomerulonephritis (Goodpasture’s disease), malignancy (thyroid cancer, melanoma, and lymphoproliferative disorders), infections (including opportunistic such as herpes virus, human papilloma virus, fungal infections, listeria, and nocardiosis) | HIV infection Hypersensitivity reactions to active ingredient or formulation excipients |
| Natalizumab (Tysabri) [19, 20, 193, 194] | Headache, fatigue, arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea, rash | PML, hypersensitivity reactions (including anaphylaxis), immunosuppression/infections (including herpes simplex virus, meningitis, and hepatitis B virus infection with acute fatal liver injury), hepatic injury | Patients who have or have had PML Patients at risk of opportunistic infections Concomitant beta IFN or glatiramer acetate therapy Known active malignancies (except cutaneous basal cell carcinoma) Hypersensitivity reactions to active ingredient or formulation excipients |
| Ocrelizumab (Ocrevus) [118] | Infusion-related reactions and upper respiratory tract infections | Infusion-related reactions, infections, neoplasms | Active hepatitis B virus infection and a history of life-threatening infusion reaction to ocrelizumab |
| Mitoxantrone (Novantrone) [142] | Nausea, alopecia, urinary tract infection, menstrual disorders (including amenorrhea), asthenia | Congestive heart failure (can result in death) may occur either during or months to years after termination of therapy. Secondary acute myeloid leukemia, infection, leukopenia, depression, bone pain, emesis, renal failure | Baseline LVEF below the lower limit of normal Pregnancy and breastfeeding Hypersensitivity reactions to active ingredient or formulation excipients |
AE adverse event, AV atrioventricular, DMT disease-modifying therapy, HIV human immunodeficiency virus, IFN interferon, LEVF left ventricular ejection fraction, MS multiple sclerosis, PML progressive multifocal leukoencephalopathy, ULN upper limit of normal
aFormerly daclizumab high-yield process (approved as ZINBRYTA®), which has a different form and structure than an earlier form of daclizumab