TABLE 3.
Descriptions of main ADRs associated with drugs for MS treatment and reported into the RAM system.
| Adverse drug reaction, n (%) | Immunostimulants | Immunosuppressants | Total (n = 13,880) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IFN β-1a (n = 3,097) | IFN β-1b (n = 541) | PEG-IFN β-1a (n = 558) | GA (n = 2,047) | Alem (n = 1,226) | Cladr (n = 72) | DMF (n = 1,326) | FNG (n = 2,652) | NTZ (n = 1,265) | OCZ (n = 340) | TRF (n = 756) | ||
| General disorders and administration site conditions | 2,302 (74.3%) | 449 (83%) | 453 (81.2%) | 1,918 (93.7%) | 457 (37.3%) | 17 (23.6%) | 172 (13%) | 365 (13.8%) | 186 (14.7%) | 115 (33.8%) | 131 (17.3%) | 6,565 |
| Pyrexia | 256 (8.3%) | 65 (12%) | 77 (13.8%) | 109 (5.3%) | 263 (21.5%) | 6 (8.3%) | 34 (2.6%) | 55 (2.1%) | 40 (3.2%) | 31 (9.1%) | 25 (3.3%) | 961 |
| Asthenia | 194 (6.3%) | 50 (9.2%) | 35 (6.3%) | 104 (5.1%) | 38 (3.1%) | 3 (4.2%) | 46 (3.5%) | 113 (4.3%) | 44 (3.5%) | 18 (5.3%) | 15 (2%) | 660 |
| Administration site pain | 226 (7.3%) | 45 (8.3%) | 17 (3%) | 313 (15.3%) | 1 (0.1%) | 2 (0.2%) | 604 | |||||
| Nervous system disorders | 622 (20.1%) | 122 (22.6%) | 83 (14.9%) | 486 (23.7%) | 404 (33%) | 24 (33.3%) | 196 (14.8%) | 507 (19.1%) | 430 (34%) | 46 (13.5%) | 170 (22.5%) | 3,090 |
| Headache | 228 (7.4%) | 31 (5.7%) | 42 (7.5%) | 90 (4.4%) | 234 (19.1%) | 10 (13.9%) | 32 (2.4%) | 110 (4.1%) | 62 (4.9%) | 16 (4.7%) | 14 (1.9%) | 869 |
| MS relapse | 131 (4.2%) | 32 (5.9%) | 10 (1.8%) | 102 (5%) | 72 (5.9%) | 6 (8.3%) | 48 (3.6%) | 66 (2.5%) | 124 (9.8%) | 2 (0.6%) | 63 (8.3%) | 656 |
| Dizziness | 26 (0.8%) | 1 (0.2%) | 6 (1.1%) | 27 (1.3%) | 10 (0.8%) | 2 (2.8%) | 11 (0.8%) | 21 (0.8%) | 29 (2.3%) | 5 (1.5%) | 1 (0.1%) | 139 |
| Skin and subcutaneous tissue disorders | 338 (10.9%) | 88 (16.3%) | 89 (15.9%) | 706 (34.5%) | 548 (44.7%) | 25 (34.7%) | 302 (22.8%) | 150 (5.7%) | 219 (17.3%) | 75 (22.1%) | 223 (29.5%) | 2,763 |
| Rash | 82 (2.6%) | 38 (7%) | 32 (5.7%) | 245 (12%) | 333 (27.2%) | 1 (1.4%) | 138 (10.4%) | 39 (1.5%) | 64 (5.1%) | 50 (14.7%) | 29 (3.8%) | 1,051 |
| Pruritus | 30 (1%) | 7 (1.3%) | 16 (2.9%) | 99 (4.8%) | 74 (6%) | 3 (4.2%) | 73 (5.5%) | 14 (0.5%) | 47 (3.7%) | 10 (2.9%) | 22 (2.9%) | 395 |
| Urticaria | 24 (0.8%) | 16 (3%) | 11 (2%) | 148 (7.2%) | 47 (3.8%) | 2 (2.8%) | 35 (2.6%) | 4 (0.2%) | 55 (4.3%) | 4 (1.2%) | 8 (1.1%) | 354 |
| Blood and lymphatic system disorders | 180 (5.8%) | 16 (3%) | 100 (17.9%) | 46 (2.2%) | 197 (16.1%) | 30 (41.7%) | 274 (20.7%) | 1,074 (40.5%) | 152 (12%) | 31 (9.1%) | 80 (10.6%) | 2,180 |
| Lymphopenia | 20 (0.6%) | 3 (0.6%) | 12 (2.2%) | 4 (0.2%) | 52 (4.2%) | 21 (29.2%) | 190 (14.3%) | 569 (21.5%) | 8 (0.6%) | 7 (2.1%) | 11 (1.5%) | 897 |
| Leukopenia | 45 (1.5%) | 2 (0.4%) | 30 (5.4%) | 3 (0.1%) | 16 (1.3%) | 1 (1.4%) | 33 (2.5%) | 334 (12.6%) | 5 (0.4%) | 5 (1.5%) | 18 (2.4%) | 492 |
| Thrombocytopenia | 36 (1.2%) | 6 (1.1%) | 15 (2.7%) | 6 (0.3%) | 34 (2.8%) | 3 (4.2%) | 6 (0.5%) | 17 (0.6%) | 25 (2%) | 15 (2%) | 163 | |
| Investigations | 292 (9.4%) | 26 (4.8%) | 28 (5%) | 70 (3.4%) | 191 (15.6%) | 10 (13.9%) | 100 (7.5%) | 1,059 (39.9%) | 112 (8.9%) | 16 (4.7%) | 119 (15.7%) | 2,023 |
| Gamma-GT increased | 16 (0.5%) | 1 (0.2%) | 5 (0.9%) | 5 (0.2%) | 5 (0.4%) | 11 (0.8%) | 266 (10%) | 7 (0.6%) | 1 (0.3%) | 18 (2.4%) | 335 | |
| ALT increased | 40 (1.3%) | 2 (0.4%) | 2 (0.4%) | 1 (<0.1%) | 6 (0.5%) | 2 (2.8%) | 11 (0.8%) | 187 (7.1%) | 5 (0.4%) | 9 (1.2%) | 265 | |
| ASP increased | 24 (0.8%) | 2 (0.4%) | 2 (0.4%) | 1 (<0.1%) | 4 (0.3%) | 1 (1.4%) | 9 (0.7%) | 101 (3.8%) | 5 (0.4%) | 3 (0.4%) | 152 | |
| Infections and infestations | 181 (5.8%) | 45 (8.3%) | 56 (10%) | 77 (3.8%) | 289 (23.6%) | 21 (29.2%) | 213 (16.1%) | 578 (21.8%) | 288 (22.8%) | 109 (32.1%) | 123 (16.3%) | 1,980 |
| Herpes zoster | 5 (0.2%) | 2 (0.4%) | 4 (0.2%) | 25 (2%) | 1 (1.4%) | 41 (3.1%) | 78 (2.9%) | 32 (2.5%) | 11 (3.2%) | 9 (1.2%) | 208 | |
| Influenza | 68 (2.2%) | 14 (2.6%) | 40 (7.2%) | 13 (0.6%) | 17 (1.4%) | 3 (0.2%) | 39 (1.5%) | 3 (0.2%) | 1 (0.3%) | 3 (0.4%) | 201 | |
| Viral infection | 11 (0.4%) | 1 (0.2%) | 2 (0.4%) | 11 (0.5%) | 16 (1.3%) | 30 (2.3%) | 34 (1.3%) | 22 (1.7%) | 17 (5%) | 16 (2.1%) | 160 | |
| Progressive multifocal leukoencephalopathy | 1 (<0.1%) | 4 (5.6%) | 7 (0.3%) | 96 (7.6%) | 2 (0.6%) | 3 (0.4%) | 113 | |||||
| Gastrointestinal disorders | 162 (5.2%) | 25 (4.6%) | 32 (5.7%) | 332 (16.2%) | 180 (14.7%) | 11 (15.3%) | 571 (43.1%) | 260 (9.8%) | 88 (7%) | 58 (17.1%) | 195 (25.8%) | 1,914 |
| Abdominal pain | 16 (0.5%) | 5 (0.9%) | 3 (0.5%) | 65 (3.2%) | 33 (2.7%) | 2 (2.8%) | 198 (14.9%) | 38 (1.4%) | 9 (0.7%) | 7 (2.1%) | 28 (3.7%) | 404 |
| Nausea | 40 (1.3%) | 5 (0.9%) | 11 (2%) | 81 (4%) | 50 (4.1%) | 2 (2.8%) | 77 (5.8%) | 44 (1.7%) | 21 (1.7%) | 11 (3.2%) | 20 (2.6%) | 362 |
| Diarrhea | 12 (0.4%) | 4 (0.7%) | 2 (0.4%) | 30 (1.5%) | 19 (1.5%) | 3 (4.2%) | 98 (7.4%) | 37 (1.4%) | 12 (0.9%) | 5 (1.5%) | 70 (9.3%) | 292 |
| Cardiac disorders | 38 (1.2%) | 9 (1.7%) | 10 (1.8%) | 197 (9.6%) | 178 (14.5%) | 2 (2.8%) | 19 (1.4%) | 671 (25.3%) | 24 (1.9%) | 14 (4.1%) | 20 (2.6%) | 1,182 |
| Bradycardia | 3 (0.1%) | 99 (8.1%) | 475 (17.9%) | 2 (0.2%) | 579 | |||||||
| Tachycardia | 5 (0.2%) | 3 (0.6%) | 4 (0.7%) | 121 (5.9%) | 58 (4.7%) | 2 (2.8%) | 8 (0.6%) | 26 (1%) | 6 (0.5%) | 7 (2.1%) | 8 (1.1%) | 248 |
| Palpitations | 5 (0.2%) | 1 (0.2%) | 47 (2.3%) | 6 (0.5%) | 2 (0.2%) | 13 (0.5%) | 1 (0.1%) | 75 | ||||
| Musculoskeletal and connective tissue disorders | 334 (10.8%) | 84 (15.5%) | 86 (15.4%) | 164 (8%) | 101 (8.2%) | 6 (8.3%) | 86 (6.5%) | 145 (5.5%) | 56 (4.4%) | 9 (2.6%) | 48 (6.3%) | 1,119 |
| Myalgia | 109 (3.5%) | 20 (3.7%) | 25 (4.5%) | 28 (1.4%) | 20 (1.6%) | 13 (1%) | 11 (0.4%) | 4 (0.3%) | 2 (0.6%) | 6 (0.8%) | 238 | |
| Arthralgia | 61 (2%) | 10 (1.8%) | 20 (3.6%) | 20 (1%) | 21 (1.7%) | 2 (2.8%) | 29 (2.2%) | 25 (0.9%) | 7 (0.6%) | 3 (0.9%) | 6 (0.8%) | 204 |
| Pain in extremity | 44 (1.4%) | 14 (2.6%) | 4 (0.7%) | 29 (1.4%) | 15 (1.2%) | 1 (1.4%) | 8 (0.6%) | 14 (0.5%) | 3 (0.2%) | 1 (0.3%) | 11 (1.5%) | 144 |
| Respiratory, thoracic and mediastinal disorders | 56 (1.8%) | 6 (1.1%) | 5 (0.9%) | 321 (15.7%) | 130 (10.6%) | 3 (4.2%) | 69 (5.2%) | 121 (4.6%) | 69 (5.5%) | 73 (21.5%) | 40 (5.3%) | 893 |
| Dyspnoea | 17 (0.5%) | 2 (0.4%) | 4 (0.7%) | 194 (9.5%) | 22 (1.8%) | 16 (1.2%) | 25 (0.9%) | 19 (1.5%) | 11 (3.2%) | 8 (1.1%) | 318 | |
| Cough | 9 (0.3%) | 1 (0.2%) | 15 (0.7%) | 28 (2.3%) | 1 (1.4%) | 23 (1.7%) | 32 (1.2%) | 11 (0.9%) | 8 (2.4%) | 10 (1.3%) | 138 | |
| Choking | 1 (<0.1%) | 37 (1.8%) | 1 (0.1%) | 2 (0.2%) | 2 (0.2%) | 43 | ||||||
| Injury, poisoning and procedural complications | 243 (7.8%) | 33 (6.1%) | 51 (9.1%) | 176 (8.6%) | 38 (3.1%) | 8 (11.1%) | 33 (2.5%) | 154 (5.8%) | 72 (5.7%) | 13 (3.8%) | 14 (1.9%) | 835 |
| Administration related reaction | 51 (1.6%) | 22 (4.1%) | 25 (4.5%) | 102 (5%) | 2 (0.2%) | 4 (0.3%) | 2 (0.6%) | 208 | ||||
| Maternal exposure during pregnancy | 8 (0.3%) | 1 (0.2%) | 5 (0.2%) | 8 (0.6%) | 39 (1.5%) | 22 (1.7%) | 83 | |||||
| Skin wound | 3 (0.1%) | 1 (0.2%) | 1 (0.2%) | 6 (0.3%) | 6 (0.5%) | 2 (0.2%) | 24 (0.9%) | 2 (0.2%) | 3 (0.9%) | 48 | ||
| Vascular disorders | 70 (2.3%) | 19 (3.5%) | 6 (1.1%) | 159 (7.8%) | 60 (4.9%) | 1 (1.4%) | 174 (13.1%) | 124 (4.7%) | 40 (3.2%) | 19 (5.6%) | 71 (9.4%) | 743 |
| Flushing | 10 (0.3%) | 4 (0.7%) | 1 (0.2%) | 76 (3.7%) | 12 (1%) | 1 (1.4%) | 140 (10.6%) | 5 (0.2%) | 4 (0.3%) | 2 (0.6%) | 1 (0.1%) | 256 |
| Hypertension | 18 (0.6%) | 5 (0.9%) | 3 (0.5%) | 7 (0.3%) | 17 (1.4%) | 2 (0.2%) | 66 (2.5%) | 6 (0.5%) | 3 (0.9%) | 65 (8.6%) | 192 | |
| Hot flushes | 14 (0.5%) | 3 (0.6%) | 2 (0.4%) | 97 (4.7%) | 9 (0.7%) | 34 (2.6%) | 7 (0.3%) | 7 (0.6%) | 2 (0.6%) | 175 | ||
| Neoplasm bening, malignant and unspecified | 107 (3.5%) | 10 (1.8%) | 2 (0.4%) | 35 (1.7%) | 18 (1.5%) | 5 (6.9%) | 68 (5.1%) | 306 (11.5%) | 100 (7.9%) | 13 (3.8%) | 51 (6.7%) | 715 |
| Breast cancer | 7 (0.2%) | 3 (0.6%) | 5 (0.2%) | 4 (0.3%) | 18 (1.4%) | 30 (1.1%) | 20 (1.6%) | 4 (1.2%) | 3 (0.4%) | 94 | ||
| Malignant melanoma | 8 (0.3%) | 1 (0.2%) | 1 (<0.1%) | 2 (2.8%) | 8 (0.6%) | 47 (1.8%) | 12 (0.9%) | 1 (0.3%) | 1 (0.1%) | 81 | ||
| Basal cell carcinoma | 6 (0.3%) | 48 (1.8%) | 2 (0.2%) | 1 (0.3%) | 1 (0.1%) | 58 | ||||||
| Psychiatric disorders | 288 (9.3%) | 30 (5.5%) | 31 (5.6%) | 84 (4.1%) | 54 (4.4%) | 33 (2.5%) | 115 (4.3%) | 37 (2.9%) | 4 (1.2%) | 17 (2.2%) | 693 | |
| Insomnia | 40 (1.3%) | 6 (1.1%) | 6 (1.1%) | 9 (0.4%) | 23 (1.9%) | 7 (0.5%) | 22 (0.8%) | 2 (0.2%) | 1 (0.1%) | 116 | ||
| Depression | 28 (0.9%) | 7 (1.3%) | 5 (0.9%) | 13 (0.6%) | 7 (0.6%) | 3 (0.2%) | 30 (1.1%) | 5 (0.4%) | 1 (0.1%) | 99 | ||
| Anxiety | 32 (1%) | 3 (0.6%) | 1 (0.2%) | 12 (0.6%) | 11 (0.9%) | 1 (0.1%) | 23 (0.9%) | 1 (0.1%) | 7 (0.9%) | 91 | ||
| Hepatobiliary disorders | 68 (2.2%) | 16 (3%) | 10 (1.8%) | 24 (1.2%) | 25 (2%) | 2 (2.8%) | 49 (3.7%) | 170 (6.4%) | 42 (3.3%) | 5 (1.5%) | 41 (5.4%) | 452 |
| Hypertransaminasaemia | 77 (2.5%) | 10 (1.8%) | 10 (1.8%) | 17 (0.8%) | 14 (1.1%) | 2 (2.8%) | 41 (3.1%) | 121 (4.6%) | 24 (1.9%) | 2 (0.6%) | 43 (5.7%) | 361 |
| Hyperbilirubinaemia | 11 (0.4%) | 1 (0.2%) | 3 (0.2%) | 2 (2.8%) | 4 (0.3%) | 57 (2.1%) | 6 (0.5%) | 1 (0.3%) | 3 (0.4%) | 88 | ||
| Liver injury | 17 (0.5%) | 3 (0.6%) | 2 (0.4%) | 4 (0.2%) | 2 (0.2%) | 7 (0.5%) | 17 (0.6%) | 15 (1.2%) | 6 (0.8%) | 73 | ||
| Metabolism and nutrition disorders | 38 (1.2%) | 7 (1.3%) | 7 (1.3%) | 19 (0.9%) | 30 (2.4%) | 24 (1.8%) | 233 (8.8%) | 17 (1.3%) | 4 (1.2%) | 22 (2.9%) | 401 | |
| Dyslipidaemia | 9 (0.3%) | 3 (0.5%) | 2 (0.1%) | 4 (0.3%) | 2 (0.2%) | 170 (6.4%) | 6 (0.5%) | 1 (0.3%) | 6 (0.8%) | 203 | ||
| Decreased appetite | 18 (0.6%) | 2 (0.4%) | 1 (0.2%) | 4 (0.2%) | 8 (0.6%) | 9 (0.3%) | 1 (0.1%) | 10 (1.3%) | 53 | |||
| Vitamin D deficiency | 2 (0.1%) | 2 (0.4%) | 3 (0.1%) | 17 (1.4%) | 1 (0.1%) | 24 (0.9%) | 3 (0.4%) | 52 | ||||
| Eye disorders | 96 (3.1%) | 10 (1.8%) | 2 (0.4%) | 32 (1.6%) | 26 (2.1%) | 4 (5.6%) | 22 (1.7%) | 96 (3.6%) | 35 (2.8%) | 9 (2.6%) | 6 (0.8%) | 338 |
| Vision blurred | 9 (0.3%) | 3 (0.6%) | 4 (0.2%) | 1 (0.1%) | 2 (2.8%) | 6 (0.5%) | 6 (0.2%) | 11 (0.9%) | 2 (0.6%) | 44 | ||
| Visual impairment | 13 (0.4%) | 4 (0.7%) | 2 (0.1%) | 3 (0.2%) | 1 (0.1%) | 11 (0.4%) | 7 (0.6%) | 2 (0.3%) | 43 | |||
| Visual acuity reduced | 28 (0.9%) | 1 (<0.1%) | 1 (0.1%) | 5 (0.2%) | 35 | |||||||
| Pregnancy, puerperium and perinatal conditions | 53 (1.7%) | 1 (0.2%) | 3 (0.5%) | 15 (0.7%) | 27 (2.2%) | 4 (5.6%) | 15 (1.1%) | 67 (2.5%) | 46 (3.6%) | 3 (0.9%) | 4 (0.5%) | 238 |
| Abortion | 47 (1.5%) | 1 (0.2%) | 6 (0.3%) | 8 (0.7%) | 2 (2.8%) | 13 (1%) | 17 (0.6%) | 25 (2%) | 1 (0.3%) | 4 (0.5%) | 124 | |
| Normal newborn | 2 (0.1%) | 1 (<0.1%) | 1 (0.1%) | 20 (0.8%) | 24 | |||||||
| Pregnancy | 1 (0.2%) | 1 (0.2%) | 14 (1.1%) | 1 (0.1%) | 4 (0.2%) | 1 (0.1%) | 1 (0.3%) | 23 | ||||
| Reproductive system and breast disorders | 42 (1.4%) | 1 (0.2%) | 4 (0.7%) | 20 (1%) | 24 (2%) | 22 (1.7%) | 77 (2.9%) | 19 (1.5%) | 8 (2.4%) | 18 (2.4%) | 235 | |
| Amenorrhoea | 15 (0.5%) | 4 (0.2%) | 1 (0.1%) | 4 (0.3%) | 5 (0.2%) | 2 (0.3%) | 31 | |||||
| Cervical dysplasia | 2 (0.1%) | 4 (0.3%) | 3 (0.2%) | 14 (0.5%) | 6 (0.5%) | 29 | ||||||
| Dysmenorrhoea | 4 (0.1%) | 4 (0.3%) | 1 (0.1%) | 3 (0.1%) | 2 (0.3%) | 14 | ||||||
| Renal and urinary disorders | 59 (1.9%) | 7 (1.3%) | 5 (0.9%) | 22 (1.1%) | 28 (2.3%) | 13 (1%) | 61 (2.3%) | 16 (1.3%) | 6 (1.8%) | 5 (0.7%) | 222 | |
| Proteinuria | 13 (0.4%) | 8 (0.7%) | 2 (0.1%) | 1 (0.1%) | 1 (0.1%) | 25 | ||||||
| Micturition urgency | 3 (0.1%) | 14 (0.5%) | 17 | |||||||||
| Renal colic | 5 (0.2%) | 2 (0.1%) | 2 (0.2%) | 6 (0.2%) | 1 (0.1%) | 16 | ||||||
| Immune system disorders | 9 (0.3%) | 2 (0.4%) | 3 (0.5%) | 92 (4.5%) | 20 (1.6%) | 14 (1.1%) | 11 (0.4%) | 42 (3.3%) | 7 (2.1%) | 7 (0.9%) | 207 | |
| Hypersensitivity | 9 (0.3%) | 2 (0.4%) | 2 (0.4%) | 73 (3.6%) | 12 (1%) | 12 (0.9%) | 5 (0.2%) | 15 (1.2%) | 1 (0.3%) | 6 (0.8%) | 137 | |
| Anaphylactic shock | 11 (0.5%) | 1 (0.1%) | 1 (0.1%) | 1 (<0.1%) | 4 (0.3%) | 18 | ||||||
| Anaphylactic reaction | 3 (0.1%) | 1 (0.1%) | 11 (0.9%) | 1 (0.3%) | 16 | |||||||
| Endocrine disorders | 20 (0.6%) | 6 (1.1%) | 1 (<0.1%) | 142 (11.6%) | 3 (4.2%) | 1 (0.1%) | 14 (0.5%) | 1 (0.1%) | 1 (0.3%) | 4 (0.5%) | 193 | |
| Autoimmune thyroiditis | 1 (<0.1%) | 2 (0.4%) | 41 (3.3%) | 1 (<0.1%) | 45 | |||||||
| Hypothyroidism | 7 (0.2%) | 2 (0.4%) | 23 (1.9%) | 2 (2.8%) | 2 (0.1%) | 36 | ||||||
| Hyperthyroidism | 1 (0.2%) | 1 (<0.1%) | 25 (2%) | 3 (0.1%) | 1 (0.3%) | 1 (0.1%) | 32 | |||||
ADR, adverse drug reaction; Alem, alemtuzumab; ALT, alanine aminotransferase; ASP, aspartate aminotransferase; Cladr, cladribine; DMF, dimethyl fumarate; FNG, fingolimod; GA, glatiramer acetate; Gamma-GT, gamma-glutamyltransferase; IFN β-1a, interferon β-1a; IFN β-1b, interferon β-1b; MS, multiple sclerosis; NTZ, natalizumab; OCZ, ocrelizumab; PEG-IFN β-1a, peginterferon β-1a; RAM, Reports of Adverse Reactions of Medicines; TRF, teriflunomide.