Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study.
<h4>Background</h4>Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM)....
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-12-01
|
| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.1004457 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850124432544104448 |
|---|---|
| author | Yuqi Hu Le Gao Lingyue Zhou Wenlong Liu Cuiling Wei Boyan Liu Qi Sun Wenxin Tian Rachel Yui Ki Chu Song Song Franco Wing Tak Cheng Joe Kwun Nam Chan Amy Pui Pui Ng Heidi Ka Ying Lo Krystal Chi Kei Lee Wing Chung Chang William Chi Wai Wong Esther Wai Yin Chan Ian Chi Kei Wong Yi Chai Francisco Tsz Tsun Lai |
| author_facet | Yuqi Hu Le Gao Lingyue Zhou Wenlong Liu Cuiling Wei Boyan Liu Qi Sun Wenxin Tian Rachel Yui Ki Chu Song Song Franco Wing Tak Cheng Joe Kwun Nam Chan Amy Pui Pui Ng Heidi Ka Ying Lo Krystal Chi Kei Lee Wing Chung Chang William Chi Wai Wong Esther Wai Yin Chan Ian Chi Kei Wong Yi Chai Francisco Tsz Tsun Lai |
| author_sort | Yuqi Hu |
| collection | DOAJ |
| description | <h4>Background</h4>Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.<h4>Methods and findings</h4>We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use.<h4>Conclusions</h4>Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary. |
| format | Article |
| id | doaj-art-8137b69e7f084bf997775c5b30c6bbcf |
| institution | OA Journals |
| issn | 1549-1277 1549-1676 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj-art-8137b69e7f084bf997775c5b30c6bbcf2025-08-20T02:34:19ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762024-12-012112e100445710.1371/journal.pmed.1004457Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study.Yuqi HuLe GaoLingyue ZhouWenlong LiuCuiling WeiBoyan LiuQi SunWenxin TianRachel Yui Ki ChuSong SongFranco Wing Tak ChengJoe Kwun Nam ChanAmy Pui Pui NgHeidi Ka Ying LoKrystal Chi Kei LeeWing Chung ChangWilliam Chi Wai WongEsther Wai Yin ChanIan Chi Kei WongYi ChaiFrancisco Tsz Tsun Lai<h4>Background</h4>Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.<h4>Methods and findings</h4>We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use.<h4>Conclusions</h4>Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.https://doi.org/10.1371/journal.pmed.1004457 |
| spellingShingle | Yuqi Hu Le Gao Lingyue Zhou Wenlong Liu Cuiling Wei Boyan Liu Qi Sun Wenxin Tian Rachel Yui Ki Chu Song Song Franco Wing Tak Cheng Joe Kwun Nam Chan Amy Pui Pui Ng Heidi Ka Ying Lo Krystal Chi Kei Lee Wing Chung Chang William Chi Wai Wong Esther Wai Yin Chan Ian Chi Kei Wong Yi Chai Francisco Tsz Tsun Lai Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. PLoS Medicine |
| title | Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. |
| title_full | Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. |
| title_fullStr | Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. |
| title_full_unstemmed | Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. |
| title_short | Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study. |
| title_sort | rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia a population cohort study |
| url | https://doi.org/10.1371/journal.pmed.1004457 |
| work_keys_str_mv | AT yuqihu rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT legao rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT lingyuezhou rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT wenlongliu rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT cuilingwei rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT boyanliu rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT qisun rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT wenxintian rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT rachelyuikichu rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT songsong rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT francowingtakcheng rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT joekwunnamchan rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT amypuipuing rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT heidikayinglo rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT krystalchikeilee rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT wingchungchang rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT williamchiwaiwong rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT estherwaiyinchan rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT ianchikeiwong rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT yichai rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy AT franciscotsztsunlai rarebutelevatedincidenceofhematologicalmalignancyafterclozapineuseinschizophreniaapopulationcohortstudy |