During the study period from September 27, 2006, to December 31, 2023, a comprehensive dataset comprising 4,772,722 case reports from FAERS was analyzed, identifying 5,166 adverse event reports primarily associated with panitumumab after excluding duplicate entries. Among these, 1,780 adverse events (AEs) and 317 adverse drug reactions (ADRs) specifically linked to panitumumab were identified. The fluctuating trend in adverse event reports related to panitumumab is depicted in Fig. 1.
Since panitumumab was approved on September 27, 2006, it did not have the fewest adverse events (AEs) reported in 2007, possibly due to its widespread early adoption after approval. The overall trend fluctuated around 300 AEs but showed an upward trajectory. Exceptions include 197 AEs reported in 2013 and 177 AEs reported in 2020 (the lowest number of AEs reported since panitumumab was approved by the FDA on September 27, 2006). The years 2022 and 2023 also marked new highs in reported AEs. Therefore, monitoring the safety of panitumumab is of crucial significance.
Additionally, detailed clinical characteristics of the events associated with panitumumab are described in Table 2.
Table 2
The features of reports associated with panitumumab from September 2006 to December 2023.
| Panitumumab |
| Case Number | Percentage(%) |
Total counts | 5166 | |
Gender | | |
Male | 2511 | 78.37% |
Female | 1459 | 45.54% |
Unknown | 1196 | 37.33% |
Age | | |
<20 | 7 | 0.22% |
20–29 | 12 | 0.37% |
30–39 | 87 | 2.72% |
40–49 | 237 | 7.40% |
50–59 | 513 | 16.01% |
60–69 | 807 | 25.19% |
70–79 | 687 | 21.44% |
>80 | 237 | 7.40% |
Unknown | 2579 | 80.50% |
Reported Counties(the top ranked) | | |
US (United States) | 1763 | 55.02% |
JP(Japan) | 1041 | 32.49% |
FR(France) | 230 | 7.18% |
DE(Germany) | 228 | 7.12% |
IT(Italy) | 195 | 6.09% |
Poland | 147 | 4.59% |
Spanis | 114 | 3.56% |
AU(Australia) | 104 | 3.25% |
CA(Canada) | 90 | 2.81% |
Turkey | 76 | 2.37% |
Brazil | 53 | 1.65% |
Mexico | 44 | 1.37% |
Russian Federation | 27 | 0.84% |
Sweden | 22 | 0.69% |
Norway | 16 | 0.50% |
India | 13 | 0.41% |
Egypt | 11 | 0.34% |
CN(China) | 8 | 0.25% |
South Africa | 6 | 0.19% |
Other | 766 | 23.91% |
Serious Outcomes | | |
Congenital Anomaly | 1 | 0.03% |
Death | 825 | 25.75% |
Disability | 67 | 2.09% |
Hospitalization-initial or Prolonged | 1601 | 49.97% |
Life-threatening | 269 | 8.40% |
Requred Intervention to Prevent Permanent Impairmnt Damage | 4 | 0.12% |
Other | 2655 | 74.88% |
Among the population experiencing all AEs, males (2511, 78.37%) outnumbered females (1459, 45.54%) by a factor of 1.72. Regarding age distribution, each age group, spanning 10 years, exhibited a gradual incline initially, followed by a subsequent decline. The distribution is as follows: <20 (7, 0.22%), 20–29 (12, 0.37%), 30–39 (87, 2.72%), 40–49 (237, 7.40%), 50–59 (513, 16.01%), and 60–69 (807, 25.19%). Subsequently, there was a gradual decrease in the 70–79 age group (687, 21.44%) and > 80 (237, 7.40%).
Additionally, the top-ranked countries for panitumumab consumption were the United States (1763, 55.02%), Japan (1041, 32.49%), France (230, 7.18%), Germany (228, 7.12%), Italy (195, 6.09%), Poland (147, 4.59%), Spain (114, 3.56%), Australia (104, 3.25%), Canada (90, 2.81%), Turkey (76, 2.37%), Brazil (53, 1.65%), Mexico (44, 1.37%), Russian Federation (27, 0.84%), Sweden (22, 0.69%), Norway (16, 0.50%), India (13, 0.41%), Egypt (11, 0.34%), China (8, 0.25%), and South Africa (6, 0.19%).
The most prevalent AEs were Hospitalization-initial or Prolonged (1,601, 49.97%), accounting for nearly half of all AEs. Following this, the occurrences were death (825, 25.75%), life-threatening (269, 8.40%), and disability (67, 2.09%). The least prevalent were Required Intervention to Prevent Permanent Impairment Damage (4, 0.12%) and disability (1, 0.03%).
3.2. System Organ Class Level-associated signal detections
Table 3 presents the results of signal detection analysis for panitumumab at the System Organ Class (SOC) level. It is evident that adverse events (AEs) associated with panitumumab are widespread across 24 organ systems, indicating a relatively common occurrence of panitumumab-related AEs. Notably, the highest number of AEs was observed in "Skin and subcutaneous tissue disorders" (n = 2165), followed by "Gastrointestinal disorders" (n = 874), "General disorders and administration site conditions" (n = 824), "Metabolism and nutrition disorders" (n = 752), "Blood and lymphatic system disorders" (n = 590), "Neoplasms benign, malignant and unspecified (incl cysts and polyps)" (n = 461), "Infections and infestations" (n = 366), "Investigations" (n = 278), "Injury, poisoning and procedural complications" (n = 267), "Nervous system disorders" (n = 234), and "Vascular disorders" (n = 203). Many of these adverse events (AEs) are closely related to the pharmacological mechanisms of panitumumab, including "Skin and subcutaneous tissue disorders," "Gastrointestinal disorders," and "Neoplasms benign, malignant and unspecified (including cysts and polyps)."
3.3 PT level-associated signal detections
Table 4 offers comprehensive statistics regarding 50 Preferred Terms (PTs) delineating adverse drug reactions (ADRs) associated with panitumumab therapy. Comprehensive data are provided in Supplemental Table 1. These ADRs are meticulously ranked based on case numbers, furnishing healthcare professionals with detailed insights to anticipate, identify, and effectively manage potential adverse reactions linked to panitumumab utilization. Such data empowers healthcare practitioners with valuable information essential for optimizing patient care during panitumumab treatment.
Table 3
Signal strength of AEs of panitumumab at the System Organ Class (SOC) level in FDA Adverse Event Reporting System (FAERS) source
System Organ Class | SOC Code | Case Number | ROR(95%CI) | PRR(95%CI) | χ2 | IC(IC025) | EBGM(EBGM05) |
Skin and subcutaneous tissue disorders | 10040785 | 2165 | 16.35 (15.47–17.28) | 9.92 (9.60-10.24) | 18042.45 | 3.30 (3.13) | 9.88 (9.34) |
Gastrointestinal disorders | 10017947 | 874 | 5.90 (5.48–6.34) | 5.07 (4.77–5.38) | 2946.41 | 2.34 (2.10) | 5.06 (4.70) |
General disorders and administration site conditions | 10018065 | 824 | 6.97 (6.47–7.51) | 6.02 (5.65–6.41) | 3530.93 | 2.59 (2.34) | 6.00 (5.57) |
Metabolism and nutrition disorders | 10027433 | 752 | 9.29 (8.60-10.04) | 8.08 (7.56–8.63) | 4734.82 | 3.01 (2.75) | 8.06 (7.46) |
Blood and lymphatic system disorders | 10005329 | 590 | 6.16 (5.65–6.71) | 5.57 (5.16–6.01) | 2252.42 | 2.47 (2.19) | 5.56 (5.10) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10029104 | 461 | 15.15 (13.77–16.68) | 13.89 (12.73–15.16) | 5514.64 | 3.79 (3.47) | 13.81 (12.54) |
Infections and infestations | 10021881 | 366 | 11.14 (10.02–12.39) | 10.42 (9.44–11.51) | 3124.26 | 3.38 (3.02) | 10.38 (9.33) |
Investigations | 10022891 | 278 | 10.20 (9.04–11.51) | 9.71 (8.65–10.88) | 2173.18 | 3.27 (2.87) | 9.67 (8.56) |
Injury, poisoning and procedural complications | 10022117 | 267 | 6.06 (5.35–6.85) | 5.80 (5.16–6.51) | 1066.26 | 2.53 (2.12) | 5.78 (5.11) |
Nervous system disorders | 10029205 | 234 | 10.43 (9.14–11.89) | 10.00 (8.82–11.34) | 1895.11 | 3.32 (2.88) | 9.96 (8.73) |
Vascular disorders | 10047065 | 203 | 5.69 (4.94–6.54) | 5.50 (4.81–6.30) | 751.29 | 2.46 (1.99) | 5.49 (4.77) |
Immune system disorders | 10021428 | 184 | 10.75 (9.28–12.46) | 10.40 (9.02–11.99) | 1561.87 | 3.37 (2.88) | 10.36 (8.94) |
Hepatobiliary disorders | 10019805 | 151 | 9.88 (8.40-11.62) | 9.62 (8.22–11.27) | 1165.33 | 3.26 (2.72) | 9.59 (8.15) |
Eye disorders | 10015919 | 96 | 17.89 (14.61–21.92) | 17.58 (14.41–21.45) | 1490.84 | 4.13 (3.46) | 17.45 (14.25) |
Respiratory, thoracic and mediastinal disorders | 10038738 | 84 | 7.23 (5.83–8.97) | 7.13 (5.76–8.82) | 442.12 | 2.83 (2.12) | 7.11 (5.73) |
Surgical and medical procedures | 10042613 | 48 | 3.64 (2.74–4.84) | 3.62 (2.73–4.80) | 91.00 | 1.85 (0.93) | 3.61 (2.72) |
Renal and urinary disorders | 10038359 | 31 | 5.52 (3.88–7.86) | 5.49 (3.87–7.81) | 113.75 | 2.45 (1.32) | 5.48 (3.85) |
Congenital, familial and genetic disorders | 10010331 | 28 | 33.37 (22.95–48.51) | 33.19 (22.88–48.16) | 861.27 | 5.03 (3.83) | 32.71 (22.5) |
Cardiac disorders | 10007541 | 21 | 3.70 (2.41–5.68) | 3.69 (2.41–5.65) | 41.12 | 1.88 (0.53) | 3.68 (2.40) |
Social circumstances | 10041244 | 9 | 6.69 (3.47–12.87) | 6.68 (3.47–12.84) | 43.33 | 2.74 (0.78) | 6.66 (3.46) |
Reproductive system and breast disorders | 10038604 | 6 | 13.82 (6.19–30.86) | 13.81 (6.19–30.79) | 70.83 | 3.78 (1.48) | 13.73 (6.15) |
Product issues | 10077536 | 5 | 5.85 (2.43–14.08) | 5.85 (2.43–14.06) | 20.04 | 2.54 (0.09) | 5.83 (2.42) |
Endocrine disorders | 10014698 | 4 | 14.34 (5.36–38.36) | 14.33 (5.36–38.30) | 49.29 | 3.83 (1.17) | 14.25 (5.33) |
Footnotes: SOC, System Organ Class; ROR, Reporting Odds Ratio; CI, Confidence Interval; PRR, Proportional Reporting Ratio; χ2, Chi-squared; IC, Information Component; EBGM, Empirical Bayesian Geometric Mean |
Table 4
The top 50 signal strength of AEs of Panitumumab ranked by Case Number at the Preferred Terms level in FDA Adverse Event Reporting System (FAERS) source.
System Organ Class | PTs | Case Number | ROR (95%CI) | PRR (95%CI) | χ2 | IC (IC025) | EBGM (EBGM05) |
Skin and subcutaneous tissue disorders | rash | 675 | 7.95 (7.33–8.62) | 7.04 (6.56–7.56) | 3555.39 | 2.81 (2.54) | 7.02 (6.48) |
Gastrointestinal disorders | diarrhoea | 482 | 3.94 (3.59–4.32) | 3.66 (3.36–3.99) | 956.01 | 1.87 (1.56) | 3.66 (3.33) |
Metabolism and nutrition disorders | hypomagnesaemia | 283 | 111.32 (98.48-125.83) | 105.28 (93.74-118.24) | 27902.19 | 6.65 (6.24) | 100.49 (88.9) |
General disorders and administration site conditions | disease progression | 255 | 9.52 (8.39–10.80) | 9.10 (8.07–10.26) | 1839.88 | 3.18 (2.76) | 9.06 (7.99) |
Skin and subcutaneous tissue disorders | dermatitis acneiform | 254 | 261.68 (229.15-298.84) | 248.86 (219.21-282.53) | 56307.74 | 7.80(7.36) | 223.53 (195.74) |
Blood and lymphatic system disorders | neutropenia | 240 | 8.77 (7.70–9.98) | 8.41 (7.43–9.51) | 1568.71 | 3.07 (2.63) | 8.38 (7.36) |
Skin and subcutaneous tissue disorders | skin toxicity | 231 | 233.84 (203.65–268.50) | 223.43 (195.68-255.11) | 46417.15 | 7.66 (7.20) | 202.80 (176.62) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | colorectal cancer metastatic | 177 | 685.97 (578.47-813.45) | 662.51 (561.20-782.09) | 89723.84 | 8.99 (8.44) | 508.65 (428.94) |
Infections and infestations | paronychia | 166 | 242.47 (206.11-285.24) | 234.71 (200.46-274.81) | 34889.79 | 7.73 (7.19) | 212.05 (180.25) |
General disorders and administration site conditions | pyrexia | 164 | 2.53 (2.17–2.96) | 2.48 (2.13–2.89) | 146.8 | 1.31 (0.79) | 2.48 (2.12) |
Metabolism and nutrition disorders | decreased appetite | 158 | 3.42 (2.92–4.01) | 3.35 (2.87–3.91) | 262.3 | 1.74 (1.22) | 3.35 (2.85) |
Gastrointestinal disorders | stomatitis | 153 | 13.35 (11.36–15.68) | 12.98 (11.10-15.18) | 1685.68 | 3.69 (3.15) | 12.91 (10.99) |
Nervous system disorders | neuropathy peripheral | 152 | 7.89 (6.71–9.27) | 7.68 (6.57–8.99) | 883.99 | 2.94 (2.40) | 7.66 (6.52) |
Metabolism and nutrition disorders | dehydration | 148 | 6.15 (5.22–7.24) | 6.00 (5.12–7.03) | 617.85 | 2.58 (2.04) | 5.99 (5.08) |
Skin and subcutaneous tissue disorders | dry skin | 136 | 9.50 (8.01–11.27) | 9.28 (7.86–10.95) | 1002.75 | 3.21 (2.64) | 9.24 (7.79) |
Immune system disorders | interstitial lung disease | 121 | 13.15 (10.98–15.76) | 12.87 (10.78–15.35) | 1319.12 | 3.68 (3.08) | 12.80 (10.68) |
General disorders and administration site conditions | febrile neutropenia | 120 | 10.61 (8.85–12.72) | 10.39 (8.70–12.40) | 1015.62 | 3.37 (2.77) | 10.34 (8.63) |
Blood and lymphatic system disorders | anaemia | 120 | 3.34 (2.79-4.00) | 3.28 (2.75–3.92) | 191.7 | 1.71 (1.11) | 3.28 (2.74) |
Skin and subcutaneous tissue disorders | skin disorder | 119 | 16.74 (13.95–20.09) | 16.38 (13.70-19.58) | 1708.05 | 4.02 (3.42) | 16.27 (13.55) |
Blood and lymphatic system disorders | thrombocytopenia | 110 | 5.17 (4.28–6.25) | 5.08 (4.22–6.11) | 361.15 | 2.34 (1.72) | 5.07 (4.20) |
Skin and subcutaneous tissue disorders | erythema | 100 | 2.99 (2.45–3.65) | 2.95 (2.43–3.59) | 129.84 | 1.56 (0.91) | 2.95 (2.42) |
Skin and subcutaneous tissue disorders | skin reaction | 97 | 33.51 (27.37–41.03) | 32.90 (26.98–40.13) | 2957.82 | 5.02 (4.35) | 32.43 (26.49) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | colon cancer | 96 | 26.76 (21.84–32.79) | 26.28 (21.53–32.08) | 2308.45 | 4.70 (4.03) | 25.98 (21.2) |
General disorders and administration site conditions | therapy partial responder | 93 | 39.25 (31.91–48.27) | 38.56 (31.47–47.25) | 3345.09 | 5.24 (4.56) | 37.91 (30.82) |
Injury, poisoning and procedural complications | product storage error | 91 | 3.83 (3.11–4.71) | 3.78 (3.08–4.63) | 186.27 | 1.92 (1.23) | 3.77 (3.06) |
Investigations | neutrophil count decreased | 90 | 11.57 (9.39–14.26) | 11.39 (9.27–13.98) | 849.43 | 3.50 (2.81) | 11.33 (9.19) |
Vascular disorders | pulmonary embolism | 86 | 4.01 (3.24–4.96) | 3.96 (3.21–4.88) | 190.34 | 1.98 (1.28) | 3.95 (3.19) |
Hepatobiliary disorders | metastases to liver | 81 | 23.24 (18.64–28.98) | 22.89 (18.42–28.44) | 1679.25 | 4.50 (3.78) | 22.66 (18.18) |
Skin and subcutaneous tissue disorders | rash pustular | 78 | 54.51 (43.47–68.35) | 53.70 (42.97–67.11) | 3938.51 | 5.71 (4.97) | 52.44 (41.82) |
Injury, poisoning and procedural complications | circumstance or information capable of leading to medication error | 78 | 9.38 (7.50-11.73) | 9.25 (7.42–11.54) | 572.51 | 3.2 0(2.47) | 9.22 (7.37) |
General disorders and administration site conditions | mucosal inflammation | 74 | 15.43 (12.26–19.43) | 15.22 (12.13–19.10) | 977.57 | 3.92 (3.16) | 15.13 (12.01) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | malignant neoplasm progression | 71 | 3.28 (2.60–4.15) | 3.25 (2.58–4.10) | 110.88 | 1.70 (0.93) | 3.25 (2.57) |
General disorders and administration site conditions | general physical health deterioration | 69 | 3.30 (2.60–4.19) | 3.27 (2.59–4.14) | 109.09 | 1.71 (0.93) | 3.27 (2.58) |
Investigations | blood magnesium decreased | 68 | 46.69 (36.67–59.46) | 46.09 (36.31–58.51) | 2938.52 | 5.50 (4.70) | 45.16 (35.46) |
Immune system disorders | infusion related reaction | 63 | 7.69 (5.99–9.86) | 7.61 (5.95–9.72) | 360.75 | 2.92 (2.11) | 7.58 (5.91) |
Skin and subcutaneous tissue disorders | acne | 61 | 7.95 (6.18–10.24) | 7.87 (6.13–10.11) | 365.19 | 2.97 (2.14) | 7.85 (6.09) |
Metabolism and nutrition disorders | hypocalcaemia | 60 | 15.62 (12.10-20.17) | 15.45 (12.00-19.89) | 805.79 | 3.94 (3.10) | 15.35 (11.89) |
Metabolism and nutrition disorders | hypokalaemia | 60 | 7.18 (5.57–9.27) | 7.11 (5.53–9.15) | 314.5 | 2.83 (1.99) | 7.09 (5.49) |
Infections and infestations | sepsis | 59 | 2.73 (2.11–3.52) | 2.71 (2.10–3.49) | 63.63 | 1.43 (0.60) | 2.70 (2.09) |
Skin and subcutaneous tissue disorders | skin fissures | 52 | 20.08 (15.26–26.42) | 19.89 (15.16–26.09) | 924.73 | 4.3 (3.41) | 19.72 (14.98) |
Blood and lymphatic system disorders | leukopenia | 51 | 5.44 (4.12–7.16) | 5.39 (4.10–7.09) | 182.33 | 2.43 (1.53) | 5.38 (4.08) |
Eye disorders | conjunctivitis | 47 | 13.12 (9.84–17.50) | 13.01 (9.78–17.31) | 518.42 | 3.69 (2.76) | 12.94 (9.70) |
Infections and infestations | folliculitis | 46 | 43.27 (32.28–58.01) | 42.90 (32.08–57.36) | 1846.51 | 5.40 (4.44) | 42.09 (31.4) |
Skin and subcutaneous tissue disorders | palmar-plantar erythrodysaesthesia syndrome | 46 | 8.37 (6.26–11.20) | 8.31 (6.23–11.08) | 294.75 | 3.05 (2.10) | 8.28 (6.19) |
Nervous system disorders | peripheral sensory neuropathy | 43 | 41.49 (30.65–56.17) | 41.15 (30.47–55.58) | 1653.83 | 5.34 (4.35) | 40.41 (29.85) |
Gastrointestinal disorders | intestinal obstruction | 38 | 5.55 (4.03–7.64) | 5.52 (4.02–7.57) | 140.33 | 2.46 (1.43) | 5.50 (4.00) |
Skin and subcutaneous tissue disorders | skin exfoliation | 37 | 3.21 (2.32–4.44) | 3.19 (2.32–4.40) | 55.8 | 1.67 (0.63) | 3.19 (2.31) |
Respiratory, thoracic and mediastinal disorders | metastases to lung | 36 | 15.43 (11.11–21.44) | 15.33 (11.06–21.25) | 479.11 | 3.93 (2.87) | 15.23 (10.96) |
Surgical and medical procedures | surgery | 36 | 2.80 (2.02–3.89) | 2.79 (2.01–3.86) | 41.38 | 1.48 (0.42) | 2.79 (2.01) |
Skin and subcutaneous tissue disorders | dermatitis | 34 | 9.58 (6.84–13.44) | 9.53 (6.81–13.33) | 258.54 | 3.25 (2.16) | 9.49 (6.77) |
Footnotes: SOC, System Organ Class; ROR, Reporting Odds Ratio; CI, Confidence Interval; PRR, Proportional Reporting Ratio; χ2, Chi-squared; IC, Information Component; EBGM, Empirical Bayesian Geometric Mean |
The top five preferred terms (PTs) associated with panitumumab are as follows: rash (n = 675, IC025 = 2.81 (2.54)), diarrhoea (n = 482, IC025 = 1.87 (1.56)), hypomagnesaemia (n = 283, IC025 = 6.65 (6.24)), disease progression (n = 255, IC025 = 3.18 (2.76)), and dermatitis acneiform (n = 254, IC025 = 7.80(7.36)). Additionally, the top five PTs of panitumumab ranked by IC025 value are trichomegaly (n = 13, IC025 = 9.07 (7.15)), colorectal cancer metastatic (n = 177, IC025 = 8.99 (8.44)), colorectal cancer recurrent (n = 10, IC025 = 8.72 (6.62)), dermatitis acneiform (n = 254, IC025 = 7.8 (7.36)) and paronychia (n = 166, IC025 = 7.73 (7.19)).