Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project
Abstract
:1. Introduction
2. Results
2.1. Overall Results
2.2. Focus on Drugs Most Commonly Reported as Suspected
3. Discussion
3.1. Overall Results
3.2. Dimethyl Fumarate, Fingolimod and IFN Beta1a-Related ICSRs
4. Materials and Methods
4.1. FASM Project
4.1.1. Collection of Individual Case Safety Reports
4.1.2. Data Analysis
4.1.3. Compliance with Ethical Standard
5. Study Strengths and Limitations
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Appendix A. The FASM Group: Full List of Consortium Members and Their Affiliations
- 20
- I Division of Neurology Department of Advanced Medical and Surgical Sciences—“DAMSS” School of Medicine and Surgery University of Campania Luigi Vanvitelli, 81100 Naples, Italy
- 21
- Complex Operating Unit of Pharmacy, AORN A Cardarelli, 80131 Naples, Italy
- 22
- Department of Advanced Biomedical Sciences, University Federico II of Naples, 80131 Naples, Italy
- 23
- Azienda Ospedaliera S.G. Moscati, 83100 Avellino, Italy
- 24
- Azienda Ospedaliera R.N. dei Colli, 80131 Naples, Italy
- 25
- A.S.L. Caserta, 81100 Caserta, Italy
- 26
- Azienda Ospedaliera di Caserta, 81100 Caserta, Italy
- 27
- OO.RR. San Giovanni di Dio Ruggi d’Aragona, 84131 Salerno, Italy
- 28
- A.S.L. Napoli 1 Centro, 80145 Naples, Italy
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All ICSRs (n = 272) | ALE (n = 11) | CLA (n = 7) | DMF (n = 41) | FIN (n = 62) | GLA (n = 27) | IFN Beta 1a (n = 41) | IFN Beta 1b (n = 5) | NAT (n = 21) | OCR (n = 25) | PegIFN Beta 1a (n = 13) | TER (n = 19) | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Median Age (IQR) | 42 (30–50) | 39 (27–52) | 27 (21–39) | 37 (28.5–48.5) | 46 (35–53) | 43 (37–50.75) | 40 (24.5–47.5) | 54 (48–63.5) | 31 (23–45) | 42 (34–59.5) | 47 (27.5–58.5) | 50 (37–60) |
Sex | ||||||||||||
Female | 184 (67.7) | 9 (82) | 5 (71) | 30 (73) | 39 (63) | 18 (67) | 31 (76) | 1 (20) | 15 (71) | 12 (48) | 10 (77) | 14 (74) |
Male | 86 (31.6) | 2 (18) | 2 (29) | 11 (27) | 23 (37) | 9 (33) | 9 (22) | 4 (80) | 6 (29) | 13 (52) | 2 (15) | 5 (26) |
NA | 2 (0.7) | - | - | - | - | - | 1 (2) | - | - | - | 1 (8) | - |
Seriousness | ||||||||||||
Not serious | 138 (50.7) | 3 (27) | 3 (43) | 25 (61) | 26 (42) | 14 (52) | 24 (59) | 4 (80) | 8 (38) | 14 (56) | 8 (62) | 9 (47) |
Serious | 134 (49.3) | 8 (73) | 4 (57) | 16 (39) | 36 (58) | 13 (48) | 17 (41) | 1 (20) | 13 (62) | 11 (44) | 5 (38) | 10 (53) |
Outcome | ||||||||||||
Favorable | 166 (61) | 6 (55) | 2 (29) | 21 (51) | 28 (45.2) | 21 (77.8) | 29 (70.7) | 5 (100) | 13 (62) | 18 (72) | 10 (77) | 13 (68) |
Unfavorable | 57 (21) | 5 (45) | 1 (14) | 9 (22) | 17 (27.4) | 5 (18.5) | 8 (19.5) | - | 5 (24) | 4 (16) | - | 3 (16) |
NA | 49 (18) | - | 4 (57) | 11 (27) | 17 (27.4) | 1 (3.7) | 4 (9.8) | - | 3 (14) | 3 (12) | 3 (23) | 3 (16) |
N. Suspected Drugs Other Than MS Drugs | ||||||||||||
0 | 269 (99) | 11 (100) | 7 (100) | 41 (100) | 62 (100) | 26 (96.3) | 42 (100) | 5 (100) | 21 (100) | 25 (100) | 13 (100) | 17 (89) |
1 | 3 (1) | - | - | - | - | 1 (3.7) | - | - | - | - | - | 2 (11) |
N. Concomitant Drugs | ||||||||||||
0 | 186 (68.4) | 10 (91) | 4 (57) | 23 (56) | 42 (68) | 21 (77.8) | 30 (73.1) | 3 (60) | 16 (76) | 15 (60) | 9 (69.2) | 13 (68) |
1 | 40 (14.7) | - | - | 11 (27) | 10 (16) | 4 (14.8) | 4 (9.8) | - | 4 (19) | 3 (12) | 2 (15.4) | 2 (11) |
2 | 20 (7.4) | 1 (9) | 2 (29) | 3 (7.3) | 5 (8) | 1 (3.7) | 2 (4.9) | 1 (20) | 1 (5) | - | 2 (15.4) | 2 (11) |
3 | 9 (3.3) | - | - | 1 (2.4) | 1 (1.6) | - | 2 (4.9) | 1 (20) | - | 3 (12) | - | 1 (5) |
4 | 9 (3.3) | - | - | 3 (7.3) | 1 (1.6) | - | 3 (7.3) | - | - | 2 (8) | - | - |
≥5 | 8 (2.9) | - | 1 (14) | - | 3 (4.8) | 1 (3.7) | - | - | - | 2 (8) | - | 1 (5) |
Case No. | Age | Sex | Outcome | PT | Suspected Drug 1 | Suspected Drug 2 | Concomitant Medications | Causality Assessment |
---|---|---|---|---|---|---|---|---|
1 | 0 | M | Death | Preterm birth | Natalizumab | - | - | Possible |
2 | 0 | F | Death | Preterm birth | Glatiramer acetate | Methylprednisolone | - | Possible |
3 | 53 | M | Death | Respiratory distress | Ocrelizumab | - | - | Possible |
4 | 42 | F | Unchanged | Bacterial meningitis, bacterial pneumonitis | Alemtuzumab | - | - | Possible |
5 | 68 | M | Improved | Generalized tonic–clonic seizure, autoimmune encephalitis | Alemtuzumab | - | - | Possible |
6 | 48 | M | Unchanged | Limbic encephalitis | Fingolimod | - | Tamsulosin | Possible |
System Organ Class | DMF (n = 53; 100%) | FIN (n = 80; 100%) | IFN Beta 1a (n = 54; 100%) |
---|---|---|---|
Blood and Lymphatic System Disorders n. (%) | 17 (32.1) | 12 (15) | 11 (20) |
Anemia | - | - | 1 |
Leukocytosis | 1 | - | - |
Leucopenia | 1 | 4 | 5 |
Lymphocytopenia | 12 | 8 | 1 |
Neutrophilia | 1 | - | - |
Neutropenia | - | - | 3 |
Thrombocytopenia | 2 | - | 1 |
General Disorders and Administration site Conditions n. (%) | 1 (1.9) | 3 (3.75) | 24 (44) |
Flu-like symptoms | 1 | - | 16 |
Asthenia | - | 1 | 1 |
Cyst | - | 1 | - |
Wheezing | - | 1 | - |
Pyrexia | - | - | 2 |
Loss of response | 1 | ||
Injection site reaction | - | - | 4 |
Infections and Infestations n. (%) | 4 (7.5) | 15 (18.75) | 2 (4) |
Sepsis | 1 | - | - |
Spondylodiscitis | 1 | 1 | - |
Rhinitis | 1 | - | - |
Herpes zoster infection | 1 | 5 | - |
Bronchitis | - | 1 | - |
Cystitis | - | 4 | - |
Encephalitis | - | 1 | - |
Molluscum contagious | - | 2 | - |
Pneumonitis | 1 | - | |
Broncho-pneumonitis | - | - | 1 |
Cutaneous abscess | - | - | 1 |
Neoplasms Benign, Malignant and Unspecified n. (%) | 1 (1.9) | 17 (21.25) | 3 (6) |
Lymphoma | 1 | - | - |
Lung cancer | - | 1 | - |
Breast cancer | - | 3 | - |
Ovarian cancer | - | 1 | - |
Thyroid cancer | - | 1 | - |
Epithelioma | - | 1 | - |
Melanoma | - | 3 | 1 |
Metastatic gallbladder cancer | - | 1 | - |
Myomas | - | 1 | - |
Mouth cancer | - | 1 | - |
Melanocytic nevus | - | 2 | - |
Dysplastic nevus | - | 1 | - |
Anal warts | - | 1 | - |
Colorectal cancer | - | - | 1 |
Nodular fasciitis | - | - | 1 |
Investigations n. (%) | 1 (1.9) | 12 (15) | 3 (6) |
Increase in transaminases | 1 | 1 | 3 |
ALT elevation | - | 2 | - |
GGT elevation | - | 6 | - |
Cholesterol elevation | - | 1 | - |
GPT elevation | - | 2 | - |
Gastrointestinal Disorders n. (%) | 11 (20.8) | 2 (2.5) | 1 (2) |
Heartburn | 7 | - | - |
Dysphagia | 1 | - | - |
Diarrhea | 2 | - | - |
Unspecified gastrointestinal disorder | 1 | - | - |
Pancreatic insufficiency | 1 | - | |
Nausea | 1 | - | |
Oral lesion | - | - | 1 |
Skin and Subcutaneous Tissue Disorders n. (%) | 6 (11.3) | 1 (1.25) | 5 (9) |
Eczema | 2 | - | - |
Skin eruption | 2 | - | - |
Facial redness | 2 | - | - |
Skin lesion | - | 1 | - |
Sweating | - | - | 1 |
Measles rash | - | - | 1 |
Hair thinning | - | - | 1 |
Skin induration | - | - | 1 |
Skin pigmentation | - | - | 1 |
Other SOCs n. (%) | 12 (22.6) | 18 (22.5) | 5 (9) |
Congenital, familial and genetic disorders | 1 | - | - |
Hepatobiliary disorders | 1 | 3 | 2 |
Injury, poisoning and procedural complications | 2 | 2 | - |
Renal and urinary disorders | 1 | - | - |
Vascular disorders | 3 | - | - |
Respiratory, thoracic and mediastinal disorders | 4 | 2 | - |
Cardiac disorders | - | 2 | - |
Eye disorders | - | 3 | - |
Nervous system disorders | - | 6 | 1 |
Endocrine disorders | - | - | 1 |
Pregnancy, puerperium and perinatal conditions | - | - | 1 |
Median and Range of TTE by SOCs and Suspected Drugs | Dimethyl Fumarate | Fingolimod | IFN Beta 1a |
---|---|---|---|
Blood and Lymphatic System Disorders Median (IQR) Range | 224 (145–621.5) 145–1629 | 1227 (500–1529.75) 74–2575 | 1518 (223–2860) 68–3061 |
General Disorders and Administration Site Conditions Median (IQR) Range | - | 70 (0–679) 0–679 | 188 (0.25–4900) 0–706 |
Infections and Infestations Median (IQR) Range | 943 (139.75–1598.75) 0–1689 | 1486.5 (769.25–2609.75) 212–3585 | - |
Neoplasms Benign, Malignant and Unspecified Median (IQR) Range | - | 1589.5 (1040.75–2366) 464–2745 | 3681 (2760–3697) 2760–3697 |
Investigations Median (IQR) Range | - | 1396 (116.75–2197.75) 64–2474 | - |
Gastrointestinal Disorders Median (IQR) Range | 92 (33–646) 7–1460 | - | - |
Skin and Subcutaneous Tissue Disorders Median (IQR) Range | 679 (145.25–1091) 122–1430 | - | 72 (0–583.5) 0–979 |
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Maniscalco, G.T.; Brescia Morra, V.; Florio, C.; Lus, G.; Tedeschi, G.; Cianfrani, M.; Docimo, R.; Miniello, S.; Romano, F.; Sinisi, L.; et al. Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project. Pharmaceuticals 2020, 13, 466. https://doi.org/10.3390/ph13120466
Maniscalco GT, Brescia Morra V, Florio C, Lus G, Tedeschi G, Cianfrani M, Docimo R, Miniello S, Romano F, Sinisi L, et al. Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project. Pharmaceuticals. 2020; 13(12):466. https://doi.org/10.3390/ph13120466
Chicago/Turabian StyleManiscalco, Giorgia Teresa, Vincenzo Brescia Morra, Ciro Florio, Giacomo Lus, Gioacchino Tedeschi, Maddalena Cianfrani, Renato Docimo, Stefania Miniello, Felice Romano, Leonardo Sinisi, and et al. 2020. "Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project" Pharmaceuticals 13, no. 12: 466. https://doi.org/10.3390/ph13120466
APA StyleManiscalco, G. T., Brescia Morra, V., Florio, C., Lus, G., Tedeschi, G., Cianfrani, M., Docimo, R., Miniello, S., Romano, F., Sinisi, L., Spitaleri, D. L. A., Longo, G., Trama, U., Triassi, M., FASM Group, Scavone, C., & Capuano, A. (2020). Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project. Pharmaceuticals, 13(12), 466. https://doi.org/10.3390/ph13120466