Clozapine rechallenge following neutropenia using granulocyte colony-stimulating factor: A Quebec case series

Background: Clozapine has a unique efficacy profile among individuals suffering from treatment-resistant schizophrenia, but is associated with hematological side effects. The use of granulocyte colony-stimulating factors (G-CSF) to allow clozapine continuation or rechallenge has emerged as a promising option, but evidence is still scarce. Aim: To describe the largest case series so far published regarding this practice. Method: A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 x 10(9)/L since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who had received at least one dose of G-CSF, such as filgrastim, while being exposed to clozapine. All data were collected retrospectively, using patients' medical files, from January to July 2019. Results: Using G-CSF, three out of eight patients could maintain clozapine despite neutropenia episodes that otherwise would have required treatment discontinuation. The only side effect reported was mild short-lived back pain, over a mean 3-year follow-up period. In all but one case, filgrastim was used on an as-needed basis at doses of 300 mcg administered subcutaneously. Conclusion: These results suggest that the as-needed use of G-CSF is well-tolerated and may allow clozapine rechallenge in some well-selected patients, adding to the paucity of data regarding long-term safety and efficacy of this strategy. More research may help to better define potential candidates and optimal regimen of such practice.

Automated summary

The as-needed use of G-CSF may allow some patients to continue clozapine treatment despite neutropenia, with mild short-lived back pain reported as the only side effect. This approach shows promise for clozapine rechallenge in select patients and may contribute to defining the long-term safety and efficacy of this strategy. More research is needed to identify potential candidates and optimal practice regimens.