Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study
Abstract Background Interleukin (IL)-6 is one of the key cytokines in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH); however, the efficacy and safety of tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, in patients with sHLH is uncertain. Methods/Results This study in...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-022-02516-1 |
| _version_ | 1811208807349485568 |
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| author | Ju Yeon Kim Miso Kim Jin Kyun Park Eun Bong Lee Jun Won Park Junshik Hong |
| author_facet | Ju Yeon Kim Miso Kim Jin Kyun Park Eun Bong Lee Jun Won Park Junshik Hong |
| author_sort | Ju Yeon Kim |
| collection | DOAJ |
| description | Abstract Background Interleukin (IL)-6 is one of the key cytokines in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH); however, the efficacy and safety of tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, in patients with sHLH is uncertain. Methods/Results This study included 64 adult patients who were diagnosed with sHLH based on the HLH-2004 criteria. Patients were classified into two groups based on treatment regimen at baseline: tocilizumab (TCZ group, n = 8) versus other treatments (control group), including HLH-2004 protocol (n = 35), chemotherapy (n = 7), glucocorticoid alone (n = 8), and with other immunosuppressants (n = 6). Primary outcome was overall 8-week survival. Baseline characteristics between the two groups were comparable. At day 56, one patient (12.5%) in the TCZ group and twenty-eight patients (51.9%) in the control group survived. Univariable and multivariable Cox proportional hazard analysis showed that TCZ significantly increased the risk of death (adjusted hazard ratio 5.55; 95% CI 2.13–14.49). The complete or partial response rate at day 14 was 44.6% in the control group, and nil in the TCZ group. In contrast, infectious complications occurred more frequently in the TCZ group than in the control group (14.3% vs. 50.0%). Conclusion Our results suggest that tocilizumab has limited efficacy in treating adult patients with sHLH and could increase the risk of infectious complications compared to the conventional treatments. |
| first_indexed | 2024-04-12T04:29:07Z |
| format | Article |
| id | doaj.art-788429229b184374ae8616dc21fd4146 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-12T04:29:07Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-788429229b184374ae8616dc21fd41462022-12-22T03:48:00ZengBMCOrphanet Journal of Rare Diseases1750-11722022-09-011711910.1186/s13023-022-02516-1Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort studyJu Yeon Kim0Miso Kim1Jin Kyun Park2Eun Bong Lee3Jun Won Park4Junshik Hong5Division of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of MedicineAbstract Background Interleukin (IL)-6 is one of the key cytokines in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH); however, the efficacy and safety of tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, in patients with sHLH is uncertain. Methods/Results This study included 64 adult patients who were diagnosed with sHLH based on the HLH-2004 criteria. Patients were classified into two groups based on treatment regimen at baseline: tocilizumab (TCZ group, n = 8) versus other treatments (control group), including HLH-2004 protocol (n = 35), chemotherapy (n = 7), glucocorticoid alone (n = 8), and with other immunosuppressants (n = 6). Primary outcome was overall 8-week survival. Baseline characteristics between the two groups were comparable. At day 56, one patient (12.5%) in the TCZ group and twenty-eight patients (51.9%) in the control group survived. Univariable and multivariable Cox proportional hazard analysis showed that TCZ significantly increased the risk of death (adjusted hazard ratio 5.55; 95% CI 2.13–14.49). The complete or partial response rate at day 14 was 44.6% in the control group, and nil in the TCZ group. In contrast, infectious complications occurred more frequently in the TCZ group than in the control group (14.3% vs. 50.0%). Conclusion Our results suggest that tocilizumab has limited efficacy in treating adult patients with sHLH and could increase the risk of infectious complications compared to the conventional treatments.https://doi.org/10.1186/s13023-022-02516-1Secondary hemophagocytic lymphohistiocytosisInterleukin-6TocilizumabHLH-2004 protocol |
| spellingShingle | Ju Yeon Kim Miso Kim Jin Kyun Park Eun Bong Lee Jun Won Park Junshik Hong Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study Orphanet Journal of Rare Diseases Secondary hemophagocytic lymphohistiocytosis Interleukin-6 Tocilizumab HLH-2004 protocol |
| title | Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study |
| title_full | Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study |
| title_fullStr | Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study |
| title_full_unstemmed | Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study |
| title_short | Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study |
| title_sort | limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis a retrospective cohort study |
| topic | Secondary hemophagocytic lymphohistiocytosis Interleukin-6 Tocilizumab HLH-2004 protocol |
| url | https://doi.org/10.1186/s13023-022-02516-1 |
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