Table 2.
Human studies and clinical trials demonstrating α-PEG Ab responses.
| PEGylated therapeutic | Dosing regimen | α-PEG Ab isotype* | Pre-existing α-PEG Ab incidence rate | Induced/post-treatment α-PEG Ab incidence rate | Effects of α-PEG Abs | Method of α-PEG Ab detection | Ref |
|---|---|---|---|---|---|---|---|
| PEGylated bee venom or ragweed extract | 47–4,630 μg (median cumulative dose), 6–40 total weekly or biweekly injections | IgM† | Healthy donors: 0.2% (1/453) high titer (≥1:32), 4.9% (22/453) any titer Untreated allergy patients: 3.3% (3/92) high titer (≥1:32), 20.6% (19/92) any titer |
1 treatment course: 50% (29/58) high titer (≥1:32), 78% (45/58) any titer 2 treatment courses: 29% (8/28) high titer (≥1:32), 86% (24/28) any titer |
N.D. | Agglutination | 78 |
| PEG-IFN-2α (Pegasys®) or PEG-IFN-2β (PegIntron®) | N.D. | N.D. | Healthy controls: 7% (2/29) NASH patients: 7% (2/30) SLE patients: 8% (3/40) HCV patients: 44% (30/68) |
No observed increase in α-PEG | No observed effects on HCV antiviral treatment | ELISA | 79 |
| PEG-asparaginase (Oncaspar®) | 1,000 U/m2 i.v. infusion | IgG + IgM (69%) IgM (31%) |
Unmodified asparaginase group: 38% (6/16) PEG-asparaginase group: 46% (13/28)# |
Strongly correlated with rapid PEG-ASNase clearance and loss of activity | Agglutination, flow cytometryΔ | 82 | |
| PEG-PAL | 0.01–0.10 mg/kg single s.c. dose | IgG + IgM (72%) IgG (18%) |
Treatment-naïve patients: 16% (4/25) | 100% (21/21) | No observed effect on drug efficacy; associated with adverse reactions to subsequent administration of other PEGylated therapeutics | N.D. | 80 |
| PEG-uricase (Krystexxa®/Puricase) | 4–24 mg single s.c. dose | IgG + IgM | Treatment-naïve patients: 0% (0/13) | 38% (5/13) | Associated with rapid PEG-uricase clearance and loss of activity, as well as late injection site reactions | ELISAΔ | 75 |
| PEG-uricase (Krystexxa®/Puricase) | 0.5–12 mg single i.v. infusion | IgG§ | Treatment-naïve patients: 4% (1/24) | 35% (8/23) | Associated with rapid PEG- uricase clearance and loss of activity | ELISAΔ | 84 |
| PEG-uricase (Krystexxa®/Puricase) | 8 mg biweekly or monthly i.v. infusions over 6 months | IgG + IgM¶ | N.D. | 33% (69/212) | Correlated with rapid PEG- uricase clearance and loss of activity, as well as increased risk of infusion reactions¶ | ELISAΔ | 91 |
| PEG-uricase (Krystexxa®/Puricase) | 8 mg i.v. infusion at 3-week intervals, 5 doses | IgG + IgMϕ | Treatment-naïve patients: 19% (5/27) Previously treated patients: 100% (3/3) |
23% (5/22) | Associated with rapid PEG-uricase clearance and loss of efficacy, as well as a two-fold increase in the risk of infusion reactions | ELISAΔ | 81 |
| - | - | IgG (69%) IgM (18%) IgG + IgM (12%) |
Healthy donors: 27–28% (94/350–97/350) | - | - | Agglutination, flow cytometryΔ | 11 |
| - | - | IgG (61%) IgG + IgM (31%) IgM (8%) |
Healthy donors: 42% (13/31) | - | - | ELISAΔ | £ |
Indicated as percentage of total α-PEG-positive individuals;
as determined by mercaptoethanol denaturation;
serum samples were typically collected after the initial dose;
pre-existing and induced α-PEG Abs could not be differentiated because α-PEG Ab levels were determined in post-analysis;
antibody specificity to PEG confirmed through cross-reactivity and/or competition with other PEGylated agents or free PEG;
anti-PEG IgM was not evaluated;
results for anti-PEG-uricase antibodies, no comparable results available for α-PEG;
anti-PEG IgM results available for only 2 patients;
unpublished observations, Yang and Lai.
N.D., not determined or not reported; IFN, interferon; NASH, non-alcoholic steatohepatitis; SLE, systemic lupus erythematous; HCV, hepatitis C virus; PAL, phenylalanine ammonia lyase.