Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Source
2.2. Individual Cases Safety Reports Selection and Descriptive Analysis
- In the EV database, by using the line listing function, we selected all ICSRs with a PARPi as suspected drug and reported from the date of marketing authorization granted by EMA for each PARPi to 1 March 2023. In this context, the marketing authorization dates were the following: 16 December 2014 for olaparib; 16 November 2017 for niraparib; 23 May 2018 for rucaparib; and 20 June 2019 for talazoparib. Information was collected on sex, age group, reporter group, geographic origin, outcome by reaction group (10 most reported ADRs were considered), and seriousness. According to the International Council on Harmonization E2D guidelines, a case is defined as serious if it results in death, is life threatening, requires or prolongs a hospitalization, results in disability/incapacity, determines a congenital anomaly/birth defect, or results in other medically important information [38].
- Following the previous steps, qualitative and quantitative analyses were performed for the least reported outcomes of ICSRs from 1 January 2022 to 31 December 2022. For the suspected drugs in study, the main reported conditions were highlighted, considering only serious cases. All suspected ADRs reports in which PARPi were not described as the only suspected drug were excluded.
- A more detailed analysis was also performed by selecting all ICSRs with peripheral neuropathy as a reported suspected reaction from 1 January 2022 to 31 December 2022. Only serious cases were considered and information was collected on sex, age group, outcome, seriousness criteria, action taken, number of nervous disorders per ICSR, number of concomitant medicines per ICSR, and the overall number of suspected ADRs reported. All suspected ADRs reports in which PARPi were not described as the only suspected drug were excluded.
- Categorical variables were described through their absolute and relative frequency by using Office® Excel® 365 software, Version 2208 (Microsoft Corporation, Redmond, WA, USA). Pearson’s Chi-Square test was used to verify a possible relationship between the variables with a statistical significance level of 5% (p < 0.05). In this case, IBM SPSS statistics 28 (IBM, Armonk, NY, USA) was used.
- Each ICSR may include one or more suspected ADRs. ADRs included in each ICSR were analyzed according to the Medical Dictionary for Regulatory Activities (MedDRA). MedDRA is a rich and highly specific standardized medical terminology to facilitate international sharing of regulatory information for medical products used by humans (https://www.meddra.org, accessed on 8 March 2023). In this context, the suspected ADRs mentioned in each ICSR are grouped in accordance with System Organ Classes (SOC).
3. Results
3.1. Demographic Characteristics of ICSRs
3.2. Least Reported SOCs
3.3. Analysis of ICSRs—Peripheral Neuropathy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Individual Case Safety Reports (%) | |||||
---|---|---|---|---|---|
Olaparib N = 5659 | Niraparib N = 5639 | Rucaparib N = 1295 | Talazoparib N = 169 | Total N = 12,762 | |
Sex a | |||||
Male | 382 (6.8) | 19 (0.4) | 63 (4.9) | 8 (4.7) | 472 (3.7) |
Female | 5177 (91.4) | 4992 (88.5) | 1172 (90.5) | 158 (93.5) | 11,499 (90.1) |
Not specified | 100 (1.8) | 628 (11.1) | 60 (4.6) | 3 (1.8) | 791 (6.2) |
Age group | |||||
Paedriatics (<18 years) | 6 (0.1) | 1 | 0 | 2 (1.2) | 9 (0.1) |
Adult (18–64 years) | 1828 (32.3) | 1442 (25.6) | 292 (22.6) | 108 (63.9) | 3670 (28.8) |
Elderly (65–85 years) | 1303 (23.0) | 1503 (26.7) | 616 (47.6) | 33 (19.5) | 3455 (27.0) |
Very Eldery (>85 years) | 42 (0.8) | 78 (1.4) | 34 (2.6) | 0 | 154 (1.2) |
Not Specified | 2480 (43.8) | 2615 (46.3) | 353 (27.2) | 26 (15.4) | 5474 (42.9) |
Reporter group | |||||
Health care professional | 4878 (86.2) | 3660 (64.9) | 1278 (98.7) | 105 (62.1) | 9921 (77.7) |
Non-health care professional | 781 (13.8) | 1979 (35.1) | 17 (1.3) | 64 (37.9) | 2841 (22.3) |
Region | |||||
European Economic Area | 2184 (38.6) | 1018 (18.1) | 383 (29.6) | 57 (33.7) | 3642 (28.5) |
Non-European Economic Area | 3475 (61.4) | 4621 (81.9) | 912 (70.4) | 112 (66.3) | 9120 (71.5) |
Individual cases reported by system organ classes (SOC) b | |||||
General disorders and administration site conditions | 1379 | 2463 | 592 | 34 | 4468 |
Investigations | 1101 | 2733 | 417 | 41 | 4292 |
Blood and lymphatic disorders | 2232 | 1632 | 246 | 85 | 4195 |
Gastrointestinal disorders | 1276 | 2101 | 361 | 13 | 3751 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1384 | 1491 | 403 | 37 | 3315 |
Injury, poisoning and procedural complications | 582 | 1332 | 183 | 20 | 2117 |
Nervous system disorders | 448 | 1312 | 196 | 10 | 1966 |
Respiratory, thoracic and mediastinal disorders | 482 | 782 | 118 | 12 | 1394 |
Psychiatric disorders | 97 | 930 | 74 | 2 | 1103 |
Skin and subcutaneous tissue disorders | 322 | 582 | 94 | 11 | 1009 |
Number of individual cases a | |||||
Serious | 4434 (78.4) | 5152 (91.4) | 1082 (83.6) | 146 (86.4) | 10,814 (84.7) |
Non serious | 1225 (21.6) | 487 (8.6) | 213 (16.4) | 23 (13.6) | 1948 (15.3) |
Individual Case Safety Reports (%) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Olaparib Total (N = 964) | Niraparib Total (N = 1773) | Rucaparib Total (N = 234) | Talazoparib Total (N = 45) | p-Value a | ||||||
SOC | ||||||||||
Injury, poisoning and procedural complications | Off label use | 58 (6.0) | 32 (55.2) | 364 (20.5) | 160 (43.4) | 25 (10.7) | 0 | 6 (13.3) | 3 (50.0) | <0.00001 |
Product dose omission issue | 10 (17.2) | 143 (39.3) | 13 (52.0) | 1 (16.7) | ||||||
Product dose omission in error | 0 | 31 (8.5) | 0 | 0 | ||||||
Contusion | 3 (5.2) | 23 (6.3) | 0 | 0 | ||||||
Fall | 2 (3.4) | 14 (3.8) | 4 (16.0) | 1 (16.7) | ||||||
Nervous system disorders | Headache | 59 (6.1) | 8 (13.6) | 334 (18.8) | 133 (39.8) | 33 (14.1) | 9 (27.3) | 1 (2.2) | 0 | <0.00001 |
Peripheral neuropathy | 2 (3.4) | 87 (26.0) | 11 (33.3) | 0 | ||||||
Dizziness | 11 (18.6) | 82 (24.6) | 2 (6.1) | 0 | ||||||
Taste disorder | 8 (13.6) | 19 (5.7) | 1 (3.0) | 0 | ||||||
Hypoaesthesia | 2 (3.4) | 21 (6.3) | 3 (9.1) | 0 | ||||||
Respiratory, thoracic and mediastinal disorders | Dyspnoea | 87 (9.0) | 9 (10.3) | 193 (10.9) | 79 (41.0) | 19 (8.1) | 9 (47.4) | 3 (6.7) | 2 (66.7) | 0.25796 |
Interstitial lung disease | 43 (49.4) | 8 (4.1) | 0 | 0 | ||||||
Cough | 3 (3.4) | 37 (19.2) | 2 (10.5) | 0 | ||||||
Oropharyngeal pain | 2 (2.3) | 20 (10.4) | 0 | 0 | ||||||
Epistaxis | 1 (1.1) | 20 (10.4) | 0 | 0 | ||||||
Psychiatric disorders | Insomnia | 12 (1.2) | 1 (8.3) | 233 (13.1) | 155 (66.5) | 15 (6.4) | 7 (46.7) | 0 | 0 | <0.00001 |
Anxiety | 2 (16.7) | 35 (15.0) | 2 (13.3) | 0 | ||||||
Sleep disorder | 0 | 19 (8.2) | 0 | 0 | ||||||
Depression | 1 (8.3) | 14 (6.0) | 4 (26.7) | 0 | ||||||
Confusional state | 1 (8.3) | 9 (3.9) | 2 (13.3) | 0 | ||||||
Skin and subcutaneous tissue disorders | Pruritus | 35 (3.6) | 5 (14.3) | 141 (8.0) | 35 (24.8) | 9 (3.8) | 5 (55.6) | 3 (6.7) | 0 | 0.000053 |
Rash | 6 (17.1) | 21 (14.9) | 3 (33.3) | 0 | ||||||
Alopecia | 3 (8.6) | 11 (7.8) | 1 (11.1) | 1 (33.3) | ||||||
Photosensitivity reaction | 0 | 21 (14.9) | 1 (11.1) | 0 | ||||||
Erythema | 5 (14.3) | 9 (6.4) | 0 | 0 |
Individual Case Safety Reports (%) | ||||
---|---|---|---|---|
Olaparib N = 2 | Niraparib N = 87 | Rucaparib N = 11 | Total N = 100 | |
Sex | ||||
Female | 2 (100.0) | 86 (98.9) | 11 (100.0) | 99 (99.0) |
Not specified | 0 | 1 (1.1) | 0 | 1 (1.0) |
Age group | ||||
Adult (18–64 years) | 2 (100.0) | 21 (24.1) | 1 (9.1) | 24 (24.0) |
Elderly (65–85 years) | 0 | 24 (27.6) | 9 (81.8) | 33 (33.0) |
Very Eldery (>85 years) | 0 | 3 (3.5) | 0 | 3 (3.0) |
Not Specified | 0 | 39 (44.8) | 1 (9.1) | 40 (40.0) |
Outcome | ||||
Recovered/Resolved | 0 | 3 (3.5) | 0 | 3 (3.0) |
Recovering/Resolving | 0 | 5 (5.7) | 1 (9.1) | 6 (6.0) |
Not recovered/Not resolved | 1 (50.0) | 42 (48.3) | 4 (36.4) | 47 (47.0) |
Unknown | 1 (50.0) | 37 (42.5) | 6 (54.5) | 44 (44.0) |
Seriousness Criteria | ||||
Other = other medically important information | 2 (100.0) | 87 (100) | 11 (100) | 100 (100.0) |
Action Taken | ||||
Dose Reduced | 2 (100.0) | 15 (17.2) | 1 (9.1) | 18 (18.0) |
Dose Increased | 0 | 4 (4.6) | 0 | 4 (4.0) |
Drug withdrawn | 0 | 47 (54.0) | 5 (45.4) | 52 (52.0) |
Dose not changed | 0 | 12 (13.8) | 4 (36.4) | 16 (16.0) |
Unknown | 0 | 9 (10.5) | 1 (9.1) | 10 (10.0) |
Number of nervous disorders per ICSR | ||||
1 | 1 (50.0) | 42 (48.3) | 6 (54.5) | 49 (49.0) |
2 | 1 (50.0) | 27 (31.0) | 5 (45.5) | 33 (33.0) |
3 | 0 | 11 (12.7) | 0 | 11 (11.0) |
4 | 0 | 4 (4.6) | 0 | 4 (4.0) |
5 or more | 0 | 3 (3.4) | 0 | 3 (3.0) |
Concomitant medicines per ICSR | ||||
1 | 0 | 8 (9.2) | 0 | 8 (8.0) |
2 | 0 | 3 (3.4) | 0 | 3 (3.0) |
3 | 0 | 0 | 0 | 0 |
4 | 0 | 3 (3.4) | 0 | 3 (3.0) |
5 or more | 0 | 11 (12.7) | 6 (54.5) | 17 (17.0) |
Not reported | 2 (100.0) | 62 (71.3) | 5 (45.5) | 69 (69.0) |
Total suspected ADRs reported | ||||
Total number | 9 | 1134 | 152 | 1295 |
Median per ICRS | 4.5 | 11 | 10 | 10 |
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Jesus, M.; Cabral, A.; Monteiro, C.; Duarte, A.P.; Morgado, M. Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database. Curr. Oncol. 2023, 30, 6533-6545. https://doi.org/10.3390/curroncol30070479
Jesus M, Cabral A, Monteiro C, Duarte AP, Morgado M. Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database. Current Oncology. 2023; 30(7):6533-6545. https://doi.org/10.3390/curroncol30070479
Chicago/Turabian StyleJesus, Mafalda, António Cabral, Cristina Monteiro, Ana Paula Duarte, and Manuel Morgado. 2023. "Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database" Current Oncology 30, no. 7: 6533-6545. https://doi.org/10.3390/curroncol30070479
APA StyleJesus, M., Cabral, A., Monteiro, C., Duarte, A. P., & Morgado, M. (2023). Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database. Current Oncology, 30(7), 6533-6545. https://doi.org/10.3390/curroncol30070479