BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety ...BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.展开更多
A single center retrospective clinical study revealed the efficacy and safety of tofa-citinib in the treatment of ulcerative colitis(UC).This study has clinical reference value but also has some limitations.Previous s...A single center retrospective clinical study revealed the efficacy and safety of tofa-citinib in the treatment of ulcerative colitis(UC).This study has clinical reference value but also has some limitations.Previous studies,including this clinical trial,have shown that tofacitinib could be a promising treatment option for UC,but further clinical research is required to prove this point.展开更多
Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and JAK3.Its efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has...Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and JAK3.Its efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has been demonstrated in multicenter,randomized,double-blind,placebo-controlled trials.Additionally,real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted,affirming its clinical efficacy in moderate-to-severe UC.展开更多
Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combinatio...Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase(JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰcytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaL s(ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.展开更多
BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivati...BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.展开更多
BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMM...BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.展开更多
BACKGROUND An increased risk of insulin resistance(IR)has been identified in rheumatoid arthritis(RA),a chronic inflammatory disorder with elevated levels of pathogenic cytokines.Biologics targeting proinflammatory cy...BACKGROUND An increased risk of insulin resistance(IR)has been identified in rheumatoid arthritis(RA),a chronic inflammatory disorder with elevated levels of pathogenic cytokines.Biologics targeting proinflammatory cytokines can control the disease and improve insulin sensitivity in RA.Although Janus kinase(JAK)signaling can regulate cytokine receptors and participate in RA pathogenesis,it remains to be elucidated whether there is a reduction of IR in such patients under JAK inhibitor(JAKi)therapy.AIM To study the effect of JAKi treatment on the reduction of IR in RA patients with active disease.METHODS A retrospective study was carried out from April 1,2017 to March 31,2021 in a population of non-diabetic patients with active RA who were undergoing tofacitinib(TOF)therapy with 5 mg twice-daily immediate-release formulation.RESULTS Fifty-six RA patients,aged 30 years to 75 years(mean±SD:52.3±11.1)with disease activity score 28 values ranging from 4.54 to 7.37(5.82±0.74),were classified into high-IR(>2.0)and low-IR(≤2.0)groups based on their baseline homeostatic model assessment(HOMA)-IR levels.They had no previous exposure to JAKi,and received TOF therapy for no less than 6 mo.In 30 patients who were naïve to biologics,after a 24-week therapeutic period,the high-IR group showed reduced HOMA-IR levels (3.331 ± 1.036 vs 2.292 ± 0.707, P < 0.001). In another 26patients who were exposed to tumor necrosis factor-α or interleukin-6 blockers, the high-IR group,despite having achieved a decrease but with lower magnitude than in naïve patients, showedreduced HOMA-IR levels (2.924 ± 0.790 vs 2.545 ± 1.080, P = 0.018).CONCLUSIONIn this retrospective study, reduced IR was achieved in non-diabetic active RA patients following24 wk of TOF therapy.展开更多
Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the colon. Recently, tofacitinib, an oral small molecule that is an inhibitor of the Janus kinase signal transduction pathway, was ...Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the colon. Recently, tofacitinib, an oral small molecule that is an inhibitor of the Janus kinase signal transduction pathway, was proven efficacious for inducing and maintaining remission in adult patients with moderate to severe UC in three global Phase III studies. The purpose of this review is to summarize existing data on the efficacy, safety, and quality of life issues related to use tofacitinib as well as highlight recent real-world experience with this drug among patients with UC.展开更多
Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis.It may result in many infections flaring up.It is important to take precautions of all kinds(cardiovascular,malignancy,infectio...Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis.It may result in many infections flaring up.It is important to take precautions of all kinds(cardiovascular,malignancy,infections etc.)before starting tofacitinib.In this article,we have highlighted important steps where we need to take precautions before starting tofacitinib.展开更多
BACKGROUND Castleman’s disease(CD),also known as vascular follicular lymphadenopathy is a rare proliferative disease of lymphoid tissue of unknown etiology that is clinically classified as unicentric CD(UCD) or multi...BACKGROUND Castleman’s disease(CD),also known as vascular follicular lymphadenopathy is a rare proliferative disease of lymphoid tissue of unknown etiology that is clinically classified as unicentric CD(UCD) or multicentric CD(MCD) depending on lymph node involvement.At present,idiopathic MCD(iMCD) is treated with interleukin-6 inhibitors,but some patients have poor clinical outcomes.This paper reports on a case of iMCD that achieved a good therapeutic effect after treatment with glucocorticoids combined with tofacitinib.The relevant data are summarized and reported below.CASE SUMMARY This paper reports on a case of MCD in a 49-year-old female with persistent peritoneal effusion as the first manifestation and combined with multiple lymphadenopathies.Lymph node biopsy showed Castleman’s disease-like changes.The ascites subsided after treatment with glucocorticoids and tofacitinib,indicating that the treatment was effective.CONCLUSION The combination of glucocorticoids with tofacitinib is an effective regimen for the treatment of CD.展开更多
Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting...Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.展开更多
Background:Rheumatoid arthritis(RA),a chronic systemic autoimmune disease,is characterized by synovitis and progressive damage to the bone and cartilage of the joints,leading to disability and reduced quality of life....Background:Rheumatoid arthritis(RA),a chronic systemic autoimmune disease,is characterized by synovitis and progressive damage to the bone and cartilage of the joints,leading to disability and reduced quality of life.This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.Methods:The study was designed as a multicenter,open-label,randomized controlled trial.Eligible patients who were taking tofacitinib(5 mg twice daily)and had achieved sustained RA remission or low disease activity(disease activity score in 28 joints[DAS28]≤3.2)for at least 3 months were enrolled at six centers in Shanghai,China.Patients were randomly assigned(1:1:1)to one of three treatment groups:continuation of tofacitinib(5 mg twice daily);reduction in tofacitinib dose(5 mg daily);and withdrawal of tofacitinib.Efficacy and safety were assessed up to 6 months.Results:Overall,122 eligible patients were enrolled,with 41 in the continuation group,42 in the dose-reduction group,and 39 in the withdrawal group.After 6 months,the percentage of patients with a DAS28-erythrocyte sedimentation rate(ESR)of<3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups(20.5%,64.3%,and 95.1%,respectively;P<0.0001 for both comparisons).The average flare-free time was 5.8 months for the continuation group,4.7 months for the dose reduction group,and 2.4 months for the withdrawal group.Conclusion:Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy,while standard or reduced doses of tofacitinib maintained a favorable state.Trial Registration:Chictr.org,ChiCTR2000039799.展开更多
Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcripti...Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription inhibitors.These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes.With approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for UC.Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional therapies.Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic agents.The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment approaches.Despite safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.展开更多
The management of refractory ulcerative colitis(UC)and acute severe UC(ASUC)is challenging due to the lack of standardized approaches in cases resistant to multiple treatments.In this editorial,I investigate the effic...The management of refractory ulcerative colitis(UC)and acute severe UC(ASUC)is challenging due to the lack of standardized approaches in cases resistant to multiple treatments.In this editorial,I investigate the efficacy and safety of Janus kinase inhibitors,particularly upadacitinib and tofacitinib,in controlling severe and refractory disease.I highlight a notable case report by Xu et al,which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib.Furthermore,I discuss the use of tofacitinib in refractory UC and ASUC,either as monotherapy or in combination with biologics,which has shown promising response rates.Additionally,emerging evidence of upadacitinib efficacy in ASUC is presented.Overall,these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission.Further research is needed to refine treatment strategies for patients with treatment-resistant UC.展开更多
文摘BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.
基金Supported by The Scientific Research Cultivation Fund of Capital Medical University,No.PYZ23175.
文摘A single center retrospective clinical study revealed the efficacy and safety of tofa-citinib in the treatment of ulcerative colitis(UC).This study has clinical reference value but also has some limitations.Previous studies,including this clinical trial,have shown that tofacitinib could be a promising treatment option for UC,but further clinical research is required to prove this point.
文摘Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and JAK3.Its efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has been demonstrated in multicenter,randomized,double-blind,placebo-controlled trials.Additionally,real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted,affirming its clinical efficacy in moderate-to-severe UC.
文摘Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase(JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰcytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaL s(ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.
基金Supported by the Doctoral Startup Fund of Affiliated Hospital of Weifang Medical University,No.2021BKQ01.
文摘BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.
基金Supported by JSPS KAKENHI, No.17K09396, No. 17H06404, and No.20K08368.
文摘BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.
文摘BACKGROUND An increased risk of insulin resistance(IR)has been identified in rheumatoid arthritis(RA),a chronic inflammatory disorder with elevated levels of pathogenic cytokines.Biologics targeting proinflammatory cytokines can control the disease and improve insulin sensitivity in RA.Although Janus kinase(JAK)signaling can regulate cytokine receptors and participate in RA pathogenesis,it remains to be elucidated whether there is a reduction of IR in such patients under JAK inhibitor(JAKi)therapy.AIM To study the effect of JAKi treatment on the reduction of IR in RA patients with active disease.METHODS A retrospective study was carried out from April 1,2017 to March 31,2021 in a population of non-diabetic patients with active RA who were undergoing tofacitinib(TOF)therapy with 5 mg twice-daily immediate-release formulation.RESULTS Fifty-six RA patients,aged 30 years to 75 years(mean±SD:52.3±11.1)with disease activity score 28 values ranging from 4.54 to 7.37(5.82±0.74),were classified into high-IR(>2.0)and low-IR(≤2.0)groups based on their baseline homeostatic model assessment(HOMA)-IR levels.They had no previous exposure to JAKi,and received TOF therapy for no less than 6 mo.In 30 patients who were naïve to biologics,after a 24-week therapeutic period,the high-IR group showed reduced HOMA-IR levels (3.331 ± 1.036 vs 2.292 ± 0.707, P < 0.001). In another 26patients who were exposed to tumor necrosis factor-α or interleukin-6 blockers, the high-IR group,despite having achieved a decrease but with lower magnitude than in naïve patients, showedreduced HOMA-IR levels (2.924 ± 0.790 vs 2.545 ± 1.080, P = 0.018).CONCLUSIONIn this retrospective study, reduced IR was achieved in non-diabetic active RA patients following24 wk of TOF therapy.
文摘Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the colon. Recently, tofacitinib, an oral small molecule that is an inhibitor of the Janus kinase signal transduction pathway, was proven efficacious for inducing and maintaining remission in adult patients with moderate to severe UC in three global Phase III studies. The purpose of this review is to summarize existing data on the efficacy, safety, and quality of life issues related to use tofacitinib as well as highlight recent real-world experience with this drug among patients with UC.
文摘Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis.It may result in many infections flaring up.It is important to take precautions of all kinds(cardiovascular,malignancy,infections etc.)before starting tofacitinib.In this article,we have highlighted important steps where we need to take precautions before starting tofacitinib.
文摘BACKGROUND Castleman’s disease(CD),also known as vascular follicular lymphadenopathy is a rare proliferative disease of lymphoid tissue of unknown etiology that is clinically classified as unicentric CD(UCD) or multicentric CD(MCD) depending on lymph node involvement.At present,idiopathic MCD(iMCD) is treated with interleukin-6 inhibitors,but some patients have poor clinical outcomes.This paper reports on a case of iMCD that achieved a good therapeutic effect after treatment with glucocorticoids combined with tofacitinib.The relevant data are summarized and reported below.CASE SUMMARY This paper reports on a case of MCD in a 49-year-old female with persistent peritoneal effusion as the first manifestation and combined with multiple lymphadenopathies.Lymph node biopsy showed Castleman’s disease-like changes.The ascites subsided after treatment with glucocorticoids and tofacitinib,indicating that the treatment was effective.CONCLUSION The combination of glucocorticoids with tofacitinib is an effective regimen for the treatment of CD.
基金This work was partially supported by grants from the National Natural Science Foundation of China(Nos.31971302 and 82170532)the Natural Science Foundation of Guangdong Province of China(No.2019A1515011597)+2 种基金the talent young scientist supporting program of China Association for Science and Technology,the Educational Commission of Guangdong Province of China key Project(No.2020ZDZX2001)the joint grant between Guangzhou City and College(No.202102010106)Guangzhou Science and Technology Plan Project(No.202201011509).
文摘Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.
文摘Background:Rheumatoid arthritis(RA),a chronic systemic autoimmune disease,is characterized by synovitis and progressive damage to the bone and cartilage of the joints,leading to disability and reduced quality of life.This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.Methods:The study was designed as a multicenter,open-label,randomized controlled trial.Eligible patients who were taking tofacitinib(5 mg twice daily)and had achieved sustained RA remission or low disease activity(disease activity score in 28 joints[DAS28]≤3.2)for at least 3 months were enrolled at six centers in Shanghai,China.Patients were randomly assigned(1:1:1)to one of three treatment groups:continuation of tofacitinib(5 mg twice daily);reduction in tofacitinib dose(5 mg daily);and withdrawal of tofacitinib.Efficacy and safety were assessed up to 6 months.Results:Overall,122 eligible patients were enrolled,with 41 in the continuation group,42 in the dose-reduction group,and 39 in the withdrawal group.After 6 months,the percentage of patients with a DAS28-erythrocyte sedimentation rate(ESR)of<3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups(20.5%,64.3%,and 95.1%,respectively;P<0.0001 for both comparisons).The average flare-free time was 5.8 months for the continuation group,4.7 months for the dose reduction group,and 2.4 months for the withdrawal group.Conclusion:Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy,while standard or reduced doses of tofacitinib maintained a favorable state.Trial Registration:Chictr.org,ChiCTR2000039799.
文摘Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription inhibitors.These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes.With approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for UC.Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional therapies.Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic agents.The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment approaches.Despite safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.
文摘The management of refractory ulcerative colitis(UC)and acute severe UC(ASUC)is challenging due to the lack of standardized approaches in cases resistant to multiple treatments.In this editorial,I investigate the efficacy and safety of Janus kinase inhibitors,particularly upadacitinib and tofacitinib,in controlling severe and refractory disease.I highlight a notable case report by Xu et al,which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib.Furthermore,I discuss the use of tofacitinib in refractory UC and ASUC,either as monotherapy or in combination with biologics,which has shown promising response rates.Additionally,emerging evidence of upadacitinib efficacy in ASUC is presented.Overall,these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission.Further research is needed to refine treatment strategies for patients with treatment-resistant UC.
