TABLE 4.
Descriptions of main Sicilian ADRs associated with drugs for MS treatment and reported into the RNF.
| Adverse drug reaction, n (%) | Immunostimulants | Immunosuppressants | Total (n = 1,119) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IFN β-1a (n = 197) | IFN β-1b (n = 87) | PEG-IFN β-1a (n = 38) | GA (n = 103) | Alem (n = 58) | Cladr (n = 31) | DMF (n = 124) | FNG (n = 172) | NTZ (n = 212) | OCZ (n = 13) | TRF (n = 81) | FNG + DMF or + NTZ (n = 3) | ||
| General disorders and administration site conditions | 73 (37.1%) | 36 (41.4%) | 15 (39.5%) | 34 (33%) | 12 (20.7%) | 1 (3.2%) | 12 (9.7%) | 13 (7.6%) | 18 (8.5%) | 5 (6.2%) | 219 | ||
| Pyrexia | 14 (7.1%) | 11 (12.6%) | 5 (13.2%) | 4 (3.9%) | 8 (13.8%) | 2 (1.2%) | 2 (0.9%) | 2 (2.5%) | 48 | ||||
| Influenza like illness | 19 (9.6%) | 2 (2.3%) | 5 (13.2%) | 26 | |||||||||
| Administration site pain | 10 (5.1%) | 5 (5.7%) | 2 (5.3%) | 7 (6.8%) | 24 | ||||||||
| Nervous system disorders | 53 (26.9%) | 19 (21.8%) | 5 (13.2%) | 31 (30.1%) | 10 (17.2%) | 3 (9.7%) | 13 (10.5%) | 14 (8.1%) | 25 (11.8%) | 14 (17.3%) | 1 (33.3%) | 188 | |
| MS relapse | 33 (16.8%) | 13 (14.9%) | 1 (2.6%) | 20 (19.4%) | 2 (6.5%) | 11 (8.9%) | 8 (4.7%) | 13 (6.1%) | 13 (16%) | 114 | |||
| Headache | 15 (7.6%) | 2 (2.3%) | 2 (5.3%) | 3 (2.9%) | 7 (12.1%) | 1 (3.2%) | 2 (1.6%) | 1 (0.6%) | 4 (1.9%) | 1 (1.2%) | 38 | ||
| Paresthesia | 1 (0.5%) | 2 (2.3%) | 2 (1.9%) | 2 (0.9%) | 7 | ||||||||
| Blood and lymphatic system disorders | 10 (5.1%) | 4 (4.6%) | 2 (5.3%) | 1 (1%) | 9 (15.5%) | 19 (61.3%) | 36 (29%) | 57 (33.1%) | 29 (13.7%) | 1 (7.7%) | 5 (6.2%) | 173 | |
| Lymphopenia | 3 (1.5%) | 1 (2.6%) | 3 (5.2%) | 16 (51.6%) | 32 (25.8%) | 49 (28.5%) | 1 (0.5%) | 105 | |||||
| Leukopenia | 1 (0.5%) | 1 (1.1%) | 1 (2.6%) | 1 (1%) | 2 (6.5%) | 9 (7.3%) | 9 (5.2%) | 3 (3.7%) | 27 | ||||
| Thrombocytopenia | 5 (2.5%) | 2 (3.4%) | 2 (6.5%) | 10 (4.7%) | 3 (3.7%) | 22 | |||||||
| Skin and subcutaneous tissue disorders | 17 (8.6%) | 9 (10.3%) | 5 (13.2%) | 24 (23.3%) | 18 (31%) | 1 (3.2%) | 12 (9.7%) | 9 (5.2%) | 23 (10.8%) | 1 (7.7%) | 11 (13.6%) | 130 | |
| Rash | 5 (2.5%) | 7 (8%) | 1 (2.6%) | 8 (7.8%) | 14 (24.1%) | 6 (4.8%) | 1 (0.6%) | 7 (3.3%) | 1 (1.2%) | 50 | |||
| Pruritus | 2 (1%) | 2 (2.3%) | 2 (5.3%) | 6 (5.8%) | 4 (6.9%) | 4 (3.2%) | 7 (3.3%) | 1 (7.7%) | 1 (1.2%) | 29 | |||
| Urticaria | 5 (2.5%) | 1 (2.6%) | 6 (5.8%) | 2 (3.4%) | 1 (0.8%) | 9 (4.2%) | 24 | ||||||
| Infections and infestations | 11 (5.6%) | 5 (5.7%) | 5 (13.2%) | 1 (1%) | 4 (6.9%) | 4 (12.9%) | 7 (5.6%) | 25 (14.5%) | 45 (21.2%) | 4 (30.8%) | 6 (7.4%) | 117 | |
| Urinary tract infection | 2 (1%) | 1 (1.1%) | 1 (3.2%) | 3 (1.7%) | 11 (5.2%) | 2 (15.4%) | 1 (1.2%) | 21 | |||||
| Herpes zoster | 1 (2.6%) | 2 (3.4%) | 3 (2.4%) | 4 (2.3%) | 5 (2.4%) | 1 (7.7%) | 1 (1.2%) | 17 | |||||
| Progressive multifocal leukoencephalopathy | 12 (5.7%) | 1 (1.2%) | 13 | ||||||||||
| Gastrointestinal disorders | 8 (4.1%) | 1 (1.1%) | 3 (7.9%) | 12 (11.7%) | 8 (13.8%) | 1 (3.2%) | 21 (16.9%) | 11 (6.4%) | 7 (3.3%) | 3 (23.1%) | 6 (7.4%) | 81 | |
| Nausea | 4 (2%) | 1 (1.1%) | 2 (5.3%) | 3 (2.9%) | 6 (10.3%) | 1 (3.2%) | 5 (4%) | 3 (1.7%) | 1 (0.5%) | 1 (7.7%) | 27 | ||
| Vomiting | 2 (5.3%) | 4 (3.9%) | 3 (5.2%) | 1 (3.2%) | 6 (4.8%) | 2 (1.2%) | 2 (0.9%) | 1 (7.7%) | 21 | ||||
| Abdominal pain | 1 (1%) | 11 (8.9%) | 2 (0.9%) | 14 | |||||||||
| Investigations | 7 (3.6%) | 2 (2.3%) | 3 (7.9%) | 3 (2.9%) | 2 (3.4%) | 5 (4%) | 20 (11.6%) | 28 (13.2%) | 4 (4.9%) | 74 | |||
| Gamma-GT increased | 3 (1.5%) | 1 (2.6%) | 1 (1.7%) | 3 (2.4%) | 12 (7%) | 5 (2.4%) | 2 (2.5%) | 27 | |||||
| ALT increased | 2 (5.3%) | 1 (1%) | 1 (1.7%) | 3 (2.4%) | 1 (0.6%) | 3 (1.4%) | 1 (1.2%) | 12 | |||||
| JC polyomavirus test positive | 9 (4.2%) | 9 | |||||||||||
| Hepatobiliary disorders | 9 (4.6%) | 4 (4.6%) | 6 (15.8%) | 4 (3.9%) | 1 (1.7%) | 11 (8.9%) | 12 (7%) | 10 (4.7%) | 9 (11.1%) | 66 | |||
| Hypertransaminasaemia | 6 (3%) | 2 (2.3%) | 4 (10.5%) | 1 (1%) | 1 (1.7%) | 5 (4%) | 7 (4.1%) | 6 (2.8%) | 9 (11.1%) | 41 | |||
| Hyperbilirubinaemia | 3 (1.7%) | 4 (1.9%) | 1 (1.2%) | 8 | |||||||||
| Liver injury | 1 (0.5%) | 1 (1.1%) | 1 (2.6%) | 2 (1.6%) | 1 (0.5%) | 6 | |||||||
| Metabolism and nutrition disorders | 11 (5.6%) | 2 (2.3%) | 1 (2.6%) | 4 (3.9%) | 2 (3.4%) | 6 (4.8%) | 16 (9.3%) | 9 (4.2%) | 1 (7.7%) | 4 (4.9%) | 56 | ||
| Dyslipidaemia | 4 (2%) | 2 (5.3%) | 2 (3.4%) | 1 (0.8%) | 10 (5.8%) | 5 (2.4%) | 1 (7.7%) | 3 (3.7%) | 28 | ||||
| Vitamin D deficiency | 2 (1%) | 2 (2.3%) | 3 (2.9%) | 1 (0.8%) | 1 (0.6%) | 1 (1.2%) | 10 | ||||||
| Vascular disorders | 8 (4.1%) | 4 (4.6%) | 1 (2.6%) | 10 (9.7%) | 1 (1.7%) | 7 (5.6%) | 3 (1.7%) | 4 (1.9%) | 2 (15.4%) | 14 (17.3%) | 54 | ||
| Hypertension | 1 (0.5%) | 1 (1.1%) | 2 (1.2%) | 1 (7.7%) | 13 (16%) | 18 | |||||||
| Hot flushes | 1 (0.5%) | 1 (2.6%) | 6 (5.8%) | 2 (1.6%) | 3 (1.4%) | 13 | |||||||
| Flushing | 1 (0.5%) | 1 (2.6%) | 4 (3.9%) | 5 (4%) | 1 (0.5%) | 12 | |||||||
| Neoplasm benign, malignant and unspecified | 1 (0.5%) | 5 (5.7%) | 4 (3.9%) | 10 (8.1%) | 14 (8.1%) | 8 (3.8%) | 4 (4.9%) | 2 (66.6%) | 48 | ||||
| Breast cancer | 1 (1.1%) | 4 (3.2%) | 2 (1.2%) | 2 (0.9%) | 1 (33.3%) | 10 | |||||||
| Naevus | 3 (1.7%) | 1 (1.2%) | 4 | ||||||||||
| Lung cancer | 1 (1%) | 1 (0.6%) | 1 (0.5%) | 1 (1.2%) | 4 | ||||||||
| Cardiac disorders | 1 (0.5%) | 2 (2.3%) | 1 (2.6%) | 9 (8.7%) | 5 (8.6%) | 15 (8.7%) | 6 (2.8%) | 3 (3.7%) | 42 | ||||
| Tachycardia | 7 (6.8%) | 4 (6.9%) | 2 (0.9%) | 1 (1.2%) | 14 | ||||||||
| Bradycardia | 4 (2.3%) | 4 | |||||||||||
| Extrasystoles | 3 (1.7%) | 3 | |||||||||||
| Respiratory, thoracic and mediastinal disorders | 2 (1%) | 13 (12.6%) | 7 (12.1%) | 2 (1.6%) | 5 (2.9%) | 9 (4.2%) | 1 (7.7%) | 39 | |||||
| Dyspnoea | 1 (0.5%) | 12 (11.7%) | 1 (1.7%) | 1 (0.8%) | 2 (1.2%) | 2 (0.9%) | 19 | ||||||
| Cough | 1 (1%) | 4 (6.9%) | 1 (0.8%) | 1 (0.6%) | 2 (0.9%) | 9 | |||||||
| Pneumonitis | 1 (0.5%) | 2 (3.4%) | 1 (0.6%) | 1 (0.5%) | 5 | ||||||||
| Musculoskeletal and connective tissue disorders | 16 (8.1%) | 7 (8%) | 3 (7.9%) | 1 (1%) | 1 (1.7%) | 1 (0.8%) | 4 (2.3%) | 2 (0.9%) | 2 (2.5%) | 37 | |||
| Myalgia | 7 (3.6%) | 3 (3.4%) | 1 (0.8%) | 11 | |||||||||
| Arthralgia | 1 (0.5%) | 3 (7.9%) | 1 (0.8%) | 1 (0.6%) | 1 (1.2%) | 7 | |||||||
| Pain in extremity | 3 (1.5%) | 1 (0.6%) | 4 | ||||||||||
| Psychiatric disorders | 7 (3.6%) | 5 (5.7%) | 4 (10.5%) | 1 (1%) | 1 (1.7%) | 2 (1.6%) | 1 (0.6%) | 5 (2.4%) | 26 | ||||
| Depression | 3 (1.5%) | 3 (3.4%) | 1 (0.5%) | 7 | |||||||||
| Insomnia | 2 (1%) | 1 (1.1%) | 1 (2.6%) | 1 (1.7%) | 1 (0.5%) | 6 | |||||||
| Anxiety | 2 (2.3%) | 1 (0.6%) | 1 (0.5%) | 4 | |||||||||
| Eye disorders | 2 (1%) | 2 (2.3%) | 4 (3.9%) | 1 (1.7%) | 1 (3.2%) | 6 (3.5%) | 3 (1.4%) | 19 | |||||
| Eye oedema | 1 (1%) | 3 (1.7%) | 4 | ||||||||||
| Visual blurred | 1 (1.1%) | 1 (0.5%) | 2 | ||||||||||
| Exophthalmos | 1 (0.5%) | 1 (1%) | 2 | ||||||||||
| Endocrine disorders | 3 (1.5%) | 3 (3.4%) | 5 (8.6%) | 3 (9.7%) | 1 (0.8%) | 1 (0.6%) | 1 (0.5%) | 2 (2.5%) | 19 | ||||
| Thyroiditis | 2 (3.4%) | 1 (3.2%) | 1 (0.8%) | 2 (2.5%) | 6 | ||||||||
| Hypothyroidism | 1 (0.5%) | 1 (1.1%) | 2 (6.5%) | 4 | |||||||||
| Autoimmune thyroiditis | 3 (5.2%) | 3 | |||||||||||
| Immune system disorders | 1 (0.5%) | 8 (7.8%) | 1 (0.8%) | 6 (2.8%) | 1 (7.7%) | 17 | |||||||
| Hypersensitivity | 1 (0.5%) | 6 (5.8%) | 1 (0.8%) | 3 (1.4%) | 11 | ||||||||
| Anaphylactic shock | 1 (1%) | 1 (0.5%) | 2 | ||||||||||
| Anaphylactic reaction | 1 (1%) | 1 (0.5%) | 2 | ||||||||||
| Reproductive system and breast disorders | 2 (1%) | 2 (1.9%) | 1 (1.7%) | 4 (3.2%) | 3 (1.7%) | 1 (0.5%) | 2 (2.5%) | 15 | |||||
| Endometriosis | 1 (1%) | 1 (0.8%) | 2 | ||||||||||
| Breast mass | 1 (0.6%) | 1 (1.2%) | 2 | ||||||||||
| Pregnancy, puerperium and perinatal conditions | 1 (0.8%) | 11 (5.2%) | 12 | ||||||||||
| Abortion | 1 (0.8%) | 9 (4.2%) | 10 | ||||||||||
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; RNF, Rete Nazionale di Farmacovigilanza; TRF, teriflunomide.