tacrolimus and Herpes-Zoster

The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment for lupus nephritis (LN).. Meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of tacrolimus and MMF as induction therapy for LN. We systematically reviewed RCTs and prospective cohort studies with a tacrolimus dose of 3 mg daily and performed a meta-analysis of the efficacy and safety of tacrolimus as an induction treatment for LN in comparison to MMF.. The inclusion criteria were satisfied by eight studies (five RCTs and three prospective cohort studies) with a total of 408 individuals (289 for tacrolimus vs. MMF and 119 for low-dose tacrolimus). Tacrolimus and MMF had similar complete remission rates (odds ratio [OR] 1.028; 95% confidence interval [CI] 0.589-1.796; p = 0.922). The partial remission rate did not differ between the tacrolimus and MMF groups (OR 1.400; 95% CI 0.741-2.646; p = 0.300). Tacrolimus and MMF showed no differences in proteinuria, serum albumin, serum creatinine, creatinine clearance, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or extra-renal SLEDAI. The incidence of infection, severe infection, leukopenia, and hyperglycemia did not differ between the tacrolimus and MMF groups. However, herpes zoster infection was significantly less common in the tacrolimus group (OR 0.137; 95% CI 0.034-0.546; p = 0.005), whereas serum creatinine elevation was significantly higher in the tacrolimus group than in the MMF group (OR 8.148; 95% CI 1.369-48.50; p = 0.021). At 3 mg/d, tacrolimus was shown to be safe, well tolerated, and offered therapeutic benefits in all investigations.. Tacrolimus was comparable to MMF in terms of effectiveness and safety as an induction therapy for LN, with the exception of a reduced risk of herpes zoster infection and a rise in serum creatinine. In individuals with LN, 3 mg/d tacrolimus was proven to be efficacious and safe.. ZIEL: Ziel der Studie war es, die Wirksamkeit und Sicherheit von Tacrolimus und Mycophenolat-Mofetil (MMF) als Induktionstherapie und von niedrigdosiertem Tacrolimus zur Behandlung der Lupusnephritis (LN) zu untersuchen.. Es wurde eine Metaanalyse randomisierter kontrollierter Studien (RCT) durchgeführt, um die Wirksamkeit und Sicherheit von Tacrolimus und Mycophenolat-Mofetil (MMF) als Induktionstherapie bei LN zu vergleichen. Dazu wurden RCT und prospektive Kohortenstudien mit einer täglichen Tacrolimusdosis von 3 mg systematisch überprüft und eine Metaanalyse der Wirksamkeit und Sicherheit von Tacrolimus als Induktionstherapie bei LN im Vergleich zu MMF durchgeführt.. Die Einschlusskriterien wurden von 8 Studien (5 RCT und 3 prospektive Kohortenstudien) mit insgesamt 408 Personen (289 für Tacrolimus vs. MMF und 119 für niedrigdosiertes Tacrolimus) erfüllt. Tacrolimus und MMF wiesen ähnliche komplette Remissionsraten auf (Odds Ratio [OR]: 1,028; 95%-Konfidenzintervall [95%-KCI]: 0,589–1,796; p = 0,922). Die partielle Remissionsrate unterschied sich nicht zwischen der Tacrolimus- und der MMF-Gruppe (OR: 1,400; 95%-KI: 0,741–2,646; p = 0,300). Bei Tacrolimus und MMF gab es keine Unterschiede in Bezug auf Proteinurie, Serumalbumin, Serumkreatinin, Kreatininclearance, den renalen Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) oder den extrarenalen SLEDAI. Auch die Inzidenz von Infektionen, schweren Infektionen, Leukopenien und Hyperglykämien unterschied sich nicht zwischen der Tacrolimus- und der MMF-Gruppe. Allerdings war eine Herpes-zoster-Infektion in der Tacrolimusgruppe signifikant weniger häufig (OR: 0,137; 95%-KI: 0,034–0,546; p = 0,005), während der Serumkreatininanstieg in der Tacrolimusgruppe signifikant höher war als in der MMF-Gruppe (OR: 8,148; 95%-KI: 1,369–48,50; p = 0,021). Bei Gabe von 3 mg/Tag erwies sich Tacrolimus als sicher und gut verträglich und bot in sämtlichen Untersuchungen therapeutische Vorteile.. Tacrolimus war in Bezug auf Wirksamkeit und Sicherheit als Induktionstherapie bei LN mit MMF vergleichbar, außer im Hinblick auf ein vermindertes Risiko für eine Herpes-zoster-Infektion und in Bezug auf einen Anstieg des Serumkreatinins. Bei Personen mit LN stellte sich Tacrolimus in der Dosis von 3 mg/Tag als wirksam und sicher heraus.

Topics: Creatinine; Cyclophosphamide; Herpes Zoster; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Tacrolimus; Treatment Outcome

Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.. We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.. Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).. This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.

Topics: Adult; Azathioprine; Bone Marrow Diseases; Cyclophosphamide; Glucocorticoids; Herpes Zoster; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Mycophenolic Acid; Neoplasms; Network Meta-Analysis; Recurrence; Tacrolimus; Treatment Outcome

With advancement in our understanding of pathogenic mechanisms in systemic lupus erythematosus (SLE), there is tremendous enthusiasm in examining drugs, old and new, to improve outcomes. This review highlights recent trials' successes and impasses that have come to fore.. Among B-cell therapies, belimumab continues its run of successes with sustained safety and tolerability documented in a long-term extension as well as the likely approval of a subcutaneous formulation in the near future. With greater antibody-dependent cytotoxicity and less immunogenicity, there is hope for obinituzumab to succeed where its anti-CD 20 predecessors have failed. Drugs targeting type I interferons - sifalimumab and anifrolumab - have been efficacious albeit with an increase in incidence of Herpes zoster infections. There is also renewed interest in evaluating the efficacy of calcineurin inhibitors, specifically tacrolimus in the induction and maintenance of lupus nephritis. Introspection into clinical trial designs have highlighted the effects of entry criteria, end points, background medications and geographical differences on study outcomes.. There are at least 50 drugs and targets being evaluated in SLE. In addition to developing new drugs to treat lupus, future trials have to focus on more effective study designs to improve chances of trial success.

Topics: Abatacept; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Clinical Trials as Topic; Cyclosporine; Herpes Zoster; Humans; Immunosuppressive Agents; Interferon Type I; Lupus Erythematosus, Systemic; Lupus Nephritis; Maintenance Chemotherapy; Peptide Fragments; Plasma Cells; Quinolones; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes; Tacrolimus; Treatment Outcome

Infection after a kidney transplant is a serious cause of morbidity and mortality. Weighing the risks and benefits of immunosuppression is of paramount importance for patient wellbeing and transplant survival.. This is a prospective observational study exploring the variety of bacterial, viral and fungal infections occurring within the first year of living related kidney transplantation in a young transplant cohort. Fifty-one kidney transplant recipients (KTR) between the age of 18 and 45 who had a kidney transplant between Jan 2020 and Jan 2022 were enrolled and followed up for one year. Primary outcome was the occurrence of infection.. Twenty-four patients (47%) recorded a collective 33 episodes of infection. Seven patients had repeated infections and 17 had single infections. Twenty-seven patients had an uneventful year with no infections recorded. Commonest infection was lower urinary tract infection (UTI) (27.3%) followed by SARS-COV2 and Herpes Zoster (15.2%). The commonest pathogens causing lower UTI were Escherichia coli (E coli) (21.2%) and Klebsiella (18.2%). Median Tacrolimus level was (7.8) ng/ml in KTR with infection and (8.95) ng/ml in KTR without infection, p = 0.21. Median Haemoglobin (IQR) was (10.2) g/dl (7.8-14) gm/dl in KTR with infection compared to (10.8) g/dl (7.3-15.3) in KTR without infection odds ratio (OR) = 0.78, confidence interval (CI) (0.5-1.1); p = 0.16.In KTR with infection 25% had donors above the age of 60 compared to 11% in KTR without infection ( OR 2.6,CI (0.5-12), p = 0.2). Post transplant diabetes (PTDM) occurred in (25%) in KTR with infection compared to those without, but that was not statistically significant p = 0. 365.In KTR without infection, 59.3% had a preemptive transplant compared to 20.8% in the group with infection (OR = 0.18; 95% CI: 0.052-0.631; p = 0.007). Median tacrolimus was 7.8 ng/ml in KTR with single infection compared to 7.7 ng/ml in KTR with repeated infections.. This study shows that the commonest infection occurring in the first-year post kidney transplant was lower urinary tract infection followed by SARS-COV2 and Herpes Zoster. There was no difference in trough tacrolimus or haemoglobin levels between KTR who developed infection with those who did not.

Topics: Adolescent; Adult; Escherichia coli; Hemoglobins; Herpes Zoster; Humans; Kidney Transplantation; Middle Aged; RNA, Viral; Tacrolimus; Transplant Recipients; Urinary Tract Infections; Young Adult

To compare infectious risk between leflunomide versus TNF inhibitors (TNFi), and between tacrolimus versus TNFi among rheumatoid arthritis (RA) patients receiving methotrexate (MTX).. Using Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating TNFi, leflunomide, or tacrolimus. The primary outcome was any serious infections defined as a composite endpoint of serious bacterial, opportunistic, and herpes zoster infections. Secondary outcomes were individual components of the primary outcome. Propensity-score fine-stratification (PSS) and weighting were applied to adjust for confounding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing leflunomide versus TNFi, and tacrolimus versus TNFi.. Among 72,516 RA patients receiving MTX, we identified 3,336 TNFi initiators, 11,122 leflunomide initiators, and 5,136 tacrolimus initiators. Two study cohorts were 10,992 leflunomide initiators PSS-weighted on 1,623 TNFi initiators and 5,126 tacrolimus initiators PSS-weighted on 2,521 TNFi initiators. The incidence rate per 100 person-years of herpes zoster infection (3.70-4.27) was beyond 3-times that of serious bacterial infection (1.12-1.36), but opportunistic infection was relatively rare (0.11-0.23). The PSS-weighted HR [95% CI] for any serious infection was 1.03 [0.89-1.22] comparing leflunomide versus TNFi, and 0.91 [0.77-1.08] comparing tacrolimus versus TNFi. Analyses on the secondary outcomes showed consistent results.. In this nation-wide cohort study, we did not find a significant difference in the risk of serious infections (i.e., serious bacterial, opportunistic, and herpes zoster infections) between leflunomide versus TNFi, and between tacrolimus versus TNFi among RA patients receiving background MTX.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Herpes Zoster; Humans; Infections; Leflunomide; Methotrexate; Tacrolimus; Tumor Necrosis Factor Inhibitors

Topics: Antibodies, Monoclonal; Basiliximab; Calcineurin Inhibitors; Creatinine; Drug Therapy, Combination; Everolimus; Follow-Up Studies; Graft Rejection; Heart Transplantation; Herpes Zoster; Humans; Immunosuppressive Agents; Kidney Diseases; Prednisone; Recombinant Fusion Proteins; Retrospective Studies; Sirolimus; Stomatitis, Herpetic; Tacrolimus; Virus Activation

Tacrolimus ointment 0.1 percent is a well-established topical therapy for treating atopic dermatitis. Efficacy and safety have been described in several trials. Here, we present a patient with rapid onset of extensive varicella zoster infection in tacrolimus-treated skin: a side effect that has only occasionally been reported. Early recognition is important because rapid treatment for herpes zoster may lead to less frequent post-herpetic neuralgia and serious complications.

Topics: Acyclovir; Antiviral Agents; Dermatitis, Atopic; Dermatologic Agents; Drug Therapy, Combination; Female; Fusidic Acid; Herpes Zoster; Herpesvirus 3, Human; Humans; Middle Aged; Ointments; Tacrolimus; Treatment Outcome; Valacyclovir; Valine

Topics: Administration, Cutaneous; Dermatologic Agents; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Middle Aged; Tacrolimus; Treatment Outcome

Simian varicella virus (SVV) infection of primates resembles human varicella-zoster virus (VZV) infection. After primary infection, SVV becomes latent in ganglia and reactivates after immunosuppression or social and environmental stress. Herein, natural SVV infection was established in 5 cynomolgus macaques (cynos) and 10 African green (AG) monkeys. Four cynos were treated with the immunosuppressant tacrolimus (80 to 300 μg/kg/day) for 4 months and 1 was untreated (group 1). Four AG monkeys were exposed to a single dose (200 cGy) of x-irradiation (group 2), and 4 other AG monkeys were irradiated and treated with tacrolimus for 4 months (group 3); the remaining 2 AG monkeys were untreated. Zoster rash developed 1 to 2 weeks after tacrolimus treatment in 3 of 4 monkeys in group 1, 6 weeks after irradiation in 1 of 4 monkeys in group 2, and 1 to 2 weeks after irradiation in all 4 monkeys in group 3. All monkeys were euthanized 1 to 4 months after immunosuppression. SVV antigens were detected immunohistochemically in skin biopsies as well as in lungs of most monkeys. Low copy number SVV DNA was detected in ganglia from all three groups of monkeys, including controls. RNA specific for SVV ORFs 61, 63, and 9 was detected in ganglia from one immunosuppressed monkey in group 1. SVV antigens were detected in multiple ganglia from all immunosuppressed monkeys in every group, but not in controls. These results indicate that tacrolimus treatment produced reactivation in more monkeys than irradiation and tacrolimus and irradiation increased the frequency of SVV reactivation as compared to either treatment alone.

Topics: Animals; Chickenpox; Chlorocebus aethiops; Herpes Zoster; Herpesvirus 3, Human; Immunosuppressive Agents; Macaca fascicularis; Tacrolimus; Virus Activation; Virus Latency

Fulminant hepatic failure is a rare complication of infection by varicella zoster virus that is favored by immunosuppression. Within 1 week, a 43-year-old male heart transplant recipient who was admitted with epigastric pain successively developed a generalized vesicular rash, hepatitis, and secondary multiorganic failure involving encephalopathy, despite treatment with acyclovir (since Day 2) and varicella zoster virus immunoglobulin (since Day 6). Emergency liver transplantation was performed on Day 9, and 36 months later, his heart and liver function are normal.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Cyclosporine; Heart Transplantation; Hemoglobinopathies; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunosuppressive Agents; Liver Failure, Acute; Liver Function Tests; Male; Postoperative Complications; Prothrombin Time; Tacrolimus; Treatment Outcome

Topics: Absorption; Administration, Topical; Adolescent; Crohn Disease; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Tacrolimus

Cytomegalovirus (CMV) is a major infectious complication of organ transplantation and its incidence is influenced by the type and intensity of immunosuppressive therapy employed. Using a new immunosuppressive agent FK506, CMV infection was observed in 30% and CMV disease in 15% of the 26 liver transplant recipients. Delayed onset of CMV disease was noted; the mean time to the occurrence of CMV disease being 137 days posttransplantation. No graft loss or mortality could be attributed to CMV infection. Mucocutaneous herpes simplex virus (HSV) infections were encountered in 19% of the patients, while no disease could be attributed to varicella zoster virus or Epstein-Barr virus (EBV). The contribution of FK506 to a decrease in viral morbidity and associated mortality bears further investigation.

Topics: Cytomegalovirus Infections; Follow-Up Studies; Graft Rejection; Graft Survival; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Incidence; Liver Transplantation; Male; Middle Aged; Tacrolimus; Time Factors