Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The ...Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.展开更多
To the Editor,A 42-year-old man presented with a 2-month history of a generalized scattered rash,accompanied by a 1-month history of polyarthralgia.Physical examination revealed enlargement of the right-sided axillary...To the Editor,A 42-year-old man presented with a 2-month history of a generalized scattered rash,accompanied by a 1-month history of polyarthralgia.Physical examination revealed enlargement of the right-sided axillary nodes and scat-tered red maculopapular rashes on the extended side of the metacarpophalangeal of both hands,the forehead,the inner canthus,under the nose,both auricles,and back.Periungual erythema and dark red punctate rash were also observed on the digits of the fingers.The rash did not elevate above the skin surface and did not fade upon pressure.展开更多
Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is...Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis(LN);however,severe active central nervous system manifestations were excluded.Case Report:We report on a treatment-naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome(PRES)who was successfully treated via the combination of mycophenolate and belimumab,resulting in reversal of persistent headache and neuroradiologic manifestations.Conclusion:Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.展开更多
BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recen...BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.展开更多
基金supported by The Center of Innovation Program from the Japan Science and Technology Agency(JST),Grant/Award Number:JPMJCE1304 to Keishi FujioThe Ministry of Education,Culture,Sports,and the Japan Agency for Medical Research and Development(AMED),Grant/Award Numbers:JP21zf0127004,JP21tm0424221,JP22ek0410074,JP22fa627001,JP23fa627001,JP23gm1810005 to Keishi FujioJSPS Grant-in-Aid for Scientific Research(B),Grant/Award Numbers:JP19H03697,JP22H03110,JP23K24369 to Tomohisa Okamura,Chugai Pharmaceutical Co.,Ltd.,Tokyo,Japan.
文摘Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.
基金supported by grants from the National Key R&D Program of China,Grant/Award Number:2022YFE0131700 and 2022YFC3602000the National Natural Science Foundation of China Grant/Award Number:82071813 and 82271835Beijing Nova Program Grant/Award Number:20220484206.
文摘To the Editor,A 42-year-old man presented with a 2-month history of a generalized scattered rash,accompanied by a 1-month history of polyarthralgia.Physical examination revealed enlargement of the right-sided axillary nodes and scat-tered red maculopapular rashes on the extended side of the metacarpophalangeal of both hands,the forehead,the inner canthus,under the nose,both auricles,and back.Periungual erythema and dark red punctate rash were also observed on the digits of the fingers.The rash did not elevate above the skin surface and did not fade upon pressure.
基金Nature Science Foundation Project of Guangdong Province,Grant/Award Number:2019A1515011094。
文摘Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis(LN);however,severe active central nervous system manifestations were excluded.Case Report:We report on a treatment-naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome(PRES)who was successfully treated via the combination of mycophenolate and belimumab,resulting in reversal of persistent headache and neuroradiologic manifestations.Conclusion:Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.
文摘BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.
