Conclusion
PEGylated Biologics in Rheumatology: The Future or a Distraction
In the development of PEGylated uricase and CZP the potential drawbacks of PEGylation (such as heterogeneity, reduced activity and immunogenicity) did not apply or have been circumvented. Different PEGylated agents produce different levels of antibody response. Most patients treated with pegloticase develop anti-drug antibodies (which can affect efficacy), whereas very few patients treated with CZP develop anti-CZP antibodies. PEGylation increased the half-life of both agents, allowing fortnightly or monthly doses to be effective.
The nature of the molecule to be PEGylated is critically important. In the case of pegloticase, a recombinant artificial uricase with optimal properties was designed. In the case of CZP, an Fc-free Fab was used. Pegloticase has relatively poor efficacy data compared with CZP, but may be used in patients for whom there is currently no other effective drug. In contrast, CZP would have failed had it not been as effective in trials as the other TNF inhibitors available. There is therefore reason to believe that PEGylated drugs will find a role both for small groups of refractory patients and in broadening the range of available agents for wider groups of patients.
In conclusion, successful trials of PEGylated agents in gout and RA have shown that the potential gains from PEGylation can be realized whereas the potential drawbacks can be circumvented. PEGylation of relatively small molecules (as in both these examples) may be especially important in the future.