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Ocular Immunology and Inflammation Feb 2024To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis.
BACKGROUND/PURPOSE
To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis.
METHODS
Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital.
RESULTS
Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7-25) to 5.0 (IQR, 3-6.5) mg/day ( = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years ( = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects.
CONCLUSION
Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis. AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d'Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature.
Topics: Humans; Immunosuppressive Agents; Prednisone; Hydroxychloroquine; Retrospective Studies; Uveitis; Methotrexate; Mycophenolic Acid; Sarcoidosis; Treatment Outcome
PubMed: 36749910
DOI: 10.1080/09273948.2023.2165952 -
Clinical Journal of the American... Mar 2024In a phase 3 study of adults with active lupus nephritis, addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significant... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a phase 3 study of adults with active lupus nephritis, addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significant improvements in the proportion of participants achieving complete and partial renal response as well as sustained reduction in proteinuria. This analysis examined the efficacy and safety of voclosporin in a subgroup of the phase 3 study with proliferative lupus nephritis and high levels of proteinuria.
METHODS
Participants were randomized to oral voclosporin (23.7 mg twice daily) or placebo for 12 months; all participants received MMF and low-dose glucocorticoids. This analysis includes participants with class III or IV (±class V) lupus nephritis and baseline urine protein-creatinine ratio (UPCR) ≥3 g/g. Efficacy end points included complete renal response (UPCR ≤0.5 g/g with stable eGFR, low-dose glucocorticoids, and no rescue medication), partial renal response (≥50% reduction from baseline UPCR), and UPCR over time. Safety outcomes were also assessed.
RESULTS
A total of 148 participants were in the voclosporin ( n =76) and control ( n =72) arms. At 12 months, 34% and 11% of participants in the voclosporin and control arms, respectively, achieved a complete renal response (odds ratio, 4.43; 95% confidence interval [CI], 1.78 to >9.99; P = 0.001). A partial renal response was achieved by 65% of the voclosporin arm and 51% of the control arm at 12 months (odds ratio, 1.60; 95% CI, 0.8 to 3.20; P = 0.18). More voclosporin- than control-treated participants achieved UPCR ≤0.5 g/g (51% versus 26%), and voclosporin-treated participants met this end point significantly earlier (hazard ratio, 2.07; 95% CI, 1.19 to 3.60; P = 0.01). The incidence of adverse events was similar between the arms; mean eGFR values remained stable and within normal range in both arms.
CONCLUSIONS
Addition of voclosporin to MMF and low-dose glucocorticoids resulted in a significantly higher proportion of participants with proliferative lupus nephritis achieving complete and partial renal responses as well as earlier reductions in proteinuria, with no evidence of worsening kidney function.
Topics: Adult; Humans; Lupus Nephritis; Immunosuppressive Agents; Cyclosporine; Mycophenolic Acid; Proteinuria; Glucocorticoids; Treatment Outcome
PubMed: 38110196
DOI: 10.2215/CJN.0000000000000297 -
Journal of Cutaneous Medicine and... Nov 2023
Topics: Humans; Lichen Sclerosus et Atrophicus; Mycophenolic Acid; Skin; Genitalia
PubMed: 37942581
DOI: 10.1177/12034754231211327 -
Zeitschrift Fur Rheumatologie Nov 2023The 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... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
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).
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Humans; Tacrolimus; Lupus Nephritis; Mycophenolic Acid; Immunosuppressive Agents; Cyclophosphamide; Creatinine; Treatment Outcome; Herpes Zoster
PubMed: 36607421
DOI: 10.1007/s00393-022-01313-2 -
Neuroimaging Clinics of North America Feb 2024Primary central nervous system vasculitis (PCNSV) is a vasculitis limited to the brain and spinal cord. Induction therapy often consists of steroids and... (Review)
Review
Primary central nervous system vasculitis (PCNSV) is a vasculitis limited to the brain and spinal cord. Induction therapy often consists of steroids and cyclophosphamide. Maintenance therapy includes a prednisone taper and may be combined with medications such as azathioprine or mycophenolate mofetil. Relapse is common in PCNSV and an increased dose of steroids is often given, sometimes with a change in therapy. Medications such as rituximab and mycophenolate mofetil may be good alternatives in those who do not respond to initial treatment or who have relapse of disease. Mortality rates of 8% to 9% are reported in the literature.
Topics: Humans; Immunosuppressive Agents; Mycophenolic Acid; Vasculitis, Central Nervous System; Steroids; Recurrence
PubMed: 37951702
DOI: 10.1016/j.nic.2023.07.008 -
Current Opinion in Nephrology and... May 2024Systemic lupus erythematosus (SLE) can be a devastating condition, striking young patients often in their prime reproductive years. Lupus nephritis is a common and... (Review)
Review
PURPOSE OF REVIEW
Systemic lupus erythematosus (SLE) can be a devastating condition, striking young patients often in their prime reproductive years. Lupus nephritis is a common and serious complication occurring in roughly 50% of SLE cases, indicating a high likelihood of disease progression, morbidity, and mortality. As the early trials of steroid therapy, and later cyclophosphamide (CYC), therapeutic changes had been stagnant. Then came the introduction of mycophenolate mofetil (MMF) in the 2000s. After the Aspreva Lupus Management Study, there had been a dearth of trials showing positive therapy results. Since 2020, new studies have emerged for lupus nephritis involving the use of anti-BLYS agents, novel calcineurin inhibitors, CD20 blockade, and antiinterferon agents. Nephrology and rheumatology society guidelines in the United States and across the world are still catching up.
RECENT FINDINGS
Although therapeutic guidelines are being developed, updates that have come through have focused on improved diagnostic and monitoring guidelines. One theme is the recommendation of increasingly tight proteinuria control and firmer guidelines for the rapid induction of remission. The reality of multitarget therapy and the expectation of rapid induction for a more complete remission are being widely recognized.
SUMMARY
The need for more complete and more rapid induction and control of lupus nephritis is undisputed according to the evidence and guidelines, and the medications to achieve this are growing at a rate not seen over the prior two decades. What remains is a stepwise approach to recognize how to best optimize therapy. Based on available evidence, an algorithm for induction and maintenance treatment of lupus nephritis used by the University of California Irvine Lupus Nephritis clinic, is recommended.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Remission Induction; Cyclophosphamide; Lupus Erythematosus, Systemic; Treatment Outcome
PubMed: 38334499
DOI: 10.1097/MNH.0000000000000969 -
Lupus Sep 2023Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this... (Review)
Review
Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this end, we gathered a group of rheumatologists, nephrologists and a nephropathologist to review current evidence regarding diagnosis and management of LN. In this consensus paper, we summarize the key points from this meeting and provide practice guidelines for the management of kidney involvement in SLE, in view of emerging new data concerning novel agents approved recently. Renal biopsy is indispensable for the management of LN. Yet, important pearls and pitfalls need to be considered regarding indications and interpretation, which are summarized in informative tables. In new-onset LN, experts agreed that, although belimumab may be added from disease onset, patients with moderate to severe proliferative nephritis (defined as: NIH activity index > 5 plus ≥ 1 of the following: (i) NIH chronicity index > 2, (ii) proteinuria > 3 /24 h, and (iii) increase in serum creatinine > 20%) may be more likely to benefit the most. In all other patients who have already started standard-of-care treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CY), belimumab could be considered in cases with an inadequate clinical response by 3 months, or in cases that experience a nephritic flare following initial response, or have an inability to reduce the dose of glucocorticoids. In all circumstances, the drug should be given as add-on therapy, that is, in combination with a standard-of-care therapy (MMF or CY). Voclosporin could be considered for up to 3 years, in combination with MMF, in patients with heavy proteinuria (well above the nephrotic range), wherein a quick reduction of protein loss in urine is desirable to avoid the complications of the nephrotic syndrome, either as part of the initial regimen, or in cases of inadequate reduction of proteinuria with MMF. In view of the potential scarring effects, long-term administration beyond the first year requires further documentation.
Topics: Humans; Cyclophosphamide; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Proteinuria; Treatment Outcome
PubMed: 37499240
DOI: 10.1177/09612033231191944 -
ACR Open Rheumatology Oct 2023Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical...
OBJECTIVE
Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).
METHODS
Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.
RESULTS
Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84).
CONCLUSION
The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.
PubMed: 37592449
DOI: 10.1002/acr2.11598 -
Open Medicine (Warsaw, Poland) 2023The decision for definitive therapy for the treatment of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) is difficult. Patients...
The decision for definitive therapy for the treatment of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) is difficult. Patients with CTD-ILD received 0.5 g twice a day of mycophenolate mofetil for 2 years (MMF cohort, = 105) or cyclophosphamide 50 mg once every other day, and the cumulative dose of cyclophosphamide should not exceed 10 g (CYC cohort, = 140). After complete of treatment (EL), % forced vital capacity (FVC) and % diffusing capacity of the lungs for carbon monoxide were increased in both the MMF and CYC cohorts as compared to before treatment ( < 0.001 for all). There were higher changes in % FVC values and a greater number of patients with significant change in % FVC (>10% change) in the CYC cohort than in the MMF cohort ( < 0.0001 for both) at EL. Patients in the CYC cohort had higher rates of leukopenia, thrombocytopenia, serious adverse effects related to treatment(s), and death than those in the MMF cohort ( < 0.05 for all). Cyclophosphamide plus prednisolone superiorly improved % FVC compared to mycophenolate mofetil plus prednisolone. Mycophenolate mofetil and cyclophosphamide improved pulmonary function. Mycophenolate mofetil is less toxic and increased patient survival.
PubMed: 38025531
DOI: 10.1515/med-2023-0838 -
Chinese Medical Journal Jan 2024Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased... (Review)
Review
Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
Topics: Humans; Calcineurin Inhibitors; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid
PubMed: 38057972
DOI: 10.1097/CM9.0000000000002959