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Cancer Communications (London, England) Aug 2023The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) but whether the same efficacy can be achieved with reduced chemotherapy regimen of four cycles for non-bulky DLBCL patients with an IPI of 1 remains unclear. This study compared four cycles versus six cycles of chemotherapy in non-bulky low-risk DLBCL patients with negative interim positron emission tomography with computed tomography (PET-CT, Deauville 1-3), irrespective of age and other IPI risk factors (IPI 0-1).
METHODS
This was an open-label, randomized, phase III, non-inferiority trial. Patients aged 14-75 years with newly diagnosed low-risk DLBCL, according to IPI, achieving PET-CT confirmed complete response (CR) after four cycles of R-CHOP were randomized (1:1) between four cycles of rituximab (4R-CHOP+4R arm) or two cycles of R-CHOP plus two cycles of rituximab (6R-CHOP+2R arm). The primary endpoint was 2-year progression-free survival (PFS), conducted in the intention-to-treat population. Safety was assessed in patients with at least one cycle of assigned treatment. The non-inferiority margin was -8%.
RESULTS
A total of 287 patients were included in the intention-to-treat analysis, the median follow-up was 47.3 months, and the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) and 94% (95% CI, 91% to 98%) for the 4R-CHOP+4R and 6R-CHOP+2R arm. The absolute difference in 2-year PFS between the two arms was 1% (95% CI, -5% to 7%), supporting the non-inferiority of 4R-CHOP+4R. Grade 3-4 neutropenia was lower in the last four cycles of rituximab alone in the 4R-CHOP+4R arm (16.7% versus 76.9%), with decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%).
CONCLUSIONS
For newly diagnosed low-risk DLBCL patients, interim PET-CT after four cycles of R-CHOP was effective in identifying patients with Deauville 1-3 who would have a good response and Deauville 4-5 patients who might have high-risk biological features or develop resistance. Reducing the standard six cycles to four cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim PET-CT confirmed CR.
Topics: Humans; Rituximab; Positron Emission Tomography Computed Tomography; Antibodies, Monoclonal, Murine-Derived; Disease-Free Survival; Lymphoma, Large B-Cell, Diffuse; Vincristine; Cyclophosphamide; Doxorubicin; Prednisone; Positron-Emission Tomography; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37403255
DOI: 10.1002/cac2.12462 -
The Medical Letter on Drugs and... Oct 2023
Topics: Humans; Muscular Dystrophy, Duchenne; Glucocorticoids; Pregnenediones
PubMed: 37755693
DOI: 10.58347/tml.2023.1686d -
The Medical Letter on Drugs and... Aug 2023
Topics: Humans; Lymphoma, Large B-Cell, Diffuse
PubMed: 37516899
DOI: 10.58347/tml.2023.1682b -
The Lancet. Rheumatology Aug 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterised by inflammation and destruction of small to medium sized blood vessels. In the... (Randomized Controlled Trial)
Randomized Controlled Trial
The impact of treatment with avacopan on health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis: a post-hoc analysis of data from the ADVOCATE trial.
BACKGROUND
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterised by inflammation and destruction of small to medium sized blood vessels. In the previously reported ADVOCATE study, a phase 3 double-blind, double-dummy randomised controlled trial of patients with newly diagnosed or relapsing ANCA-associated vasculitis, the oral selective complement 5a receptor inhibitor avacopan was shown to be non-inferior with regard to remission induction at week 26 and superior with regard to sustained remission at week 52, compared with a prednisone taper in a standard of care regimen. In this Article, we report an in-depth analysis of prespecified and exploratory patient-reported outcomes from the ADVOCATE study, measuring health-related quality of life and health utilities.
METHODS
We did a post-hoc analysis of patient-reported outcome data from the ADVOCATE study (NCT02994927) of patients with newly diagnosed or relapsing ANCA-associated vasculitis. We analysed summary scores and individual domain scores for the prespecified health-related quality of life outcomes from ADVOCATE, which were evaluated at weeks 26 and 52 by use of the Medical Outcomes Survey 36-Item Short Form Health Survey (SF-36) version 2, the EuroQol 5-Dimensions 5-Levels Questionnaire (EQ-5D-5L), and the EQ-5D health utility measure, assessed in the modified intention-to-treat population. We also calculated the Short Form 6 Dimension (SF-6D) score as an additional health utility measure. We evaluated the proportion of patients who reported scores that met or exceeded minimum clinically important differences in health-related quality of life, and we compared scores to normative values (age-specific and sex-specific scores from healthy populations from the USA matched to the protocol population). We also evaluated the proportion of patients who reported scores that met or exceeded minimum important difference in health utility scores.
FINDINGS
331 patients were enrolled in the ADVOCATE trial, of whom 166 were in the avacopan group and 165 were in the prednisone standard of care group. In the avacopan group, the mean age was 61·2 years (SD 14·6), 98 (59%) of 166 patients were men, 68 (41%) were women, and 138 (83%) were White; in the prednisone group, the mean age was 60·5 years (14·5), 88 (54%) of 164 patients were men, 76 (46%) were women, and 140 (85%) were White. Patients treated with avacopan received approximately 2500 mg less median total prednisone up to week 52. Least squares means difference from baseline in physical component summary scores were significantly greater in patients in the avacopan group compared with those in the prednisone group at weeks 26 and 52, as well as in five of eight SF-36 domains at week 26 and two of eight SF-36 domains at week 52. The proportion of patients reporting scores equal to or greater than normative values was higher in the avacopan group than in the prednisone group across all SF-36 domains at both week 26 and 52, although the differences were not statistically significant with the exception of the role physical and vitality domains at week 26. Least squares means change from baseline in EQ-5D-5L visual analogue scale, EQ-5D health utility scores, and SF-6D health utility scores were significantly greater at week 52 in the avacopan group compared with the prednisone group.
INTERPRETATION
Patients with ANCA-associated vasculitis who received avacopan reported statistically significant and clinically meaningful improvements in health-related quality of life at 26 and 52 weeks and in health utility EQ-5D and SF-6D scores at 52 weeks. These patient-reported outcomes complement investigator assessments and support the efficacy of avacopan in patients with ANCA-associated vasculitis with use of lower prednisone doses.
FUNDING
ChemoCentryx.
Topics: Female; Humans; Male; Middle Aged; Aniline Compounds; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Nipecotic Acids; Prednisone; Quality of Life; Double-Blind Method
PubMed: 38251577
DOI: 10.1016/S2665-9913(23)00092-9 -
Multiple Sclerosis (Houndmills,... Mar 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM)....
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions.
OBJECTIVE
The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF).
METHODS
Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated.
RESULTS
A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33).
CONCLUSION
IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.
Topics: Humans; Child; Myelin-Oligodendrocyte Glycoprotein; Immunoglobulins, Intravenous; Retrospective Studies; Prednisone; Autoantibodies; Neoplasm Recurrence, Local; Mycophenolic Acid; Immunotherapy; Recurrence
PubMed: 38314479
DOI: 10.1177/13524585241226830 -
Experimental Physiology Sep 2023What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic... (Review)
Review
NEW FINDINGS
What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic targets in progressive muscle degenerative diseases such as Duchenne muscular dystrophy. What advances does it highlight? Gut microbe-derived metabolites are multifaceted signalling molecules key to muscle function, modifying pathways contributing to skeletal muscle wasting, making them a plausible target for adjunctive therapy in muscular dystrophy.
ABSTRACT
Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut-muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre- and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro-inflammatory phenotype and leaky gut barrier contributing to several of the well-known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota-directed regimen designed to optimise gut-muscle axis signalling, which could alleviate muscle wasting in DMD.
Topics: Animals; Mice; Muscular Dystrophy, Duchenne; Prednisone; Muscle, Skeletal; Glucocorticoids; Inflammation; Mice, Inbred mdx
PubMed: 37269541
DOI: 10.1113/EP091063 -
Immunity, Inflammation and Disease Oct 2023To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus...
OBJECTIVE
To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy.
METHODS
The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery.
RESULTS
Three patients in the non-PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non-PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non-PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased.
CONCLUSIONS
The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.
Topics: Humans; Female; Pregnancy; Prednisone; Antirheumatic Agents; Retrospective Studies; Plasma Exchange; Lupus Erythematosus, Systemic; Hydroxychloroquine; Treatment Outcome
PubMed: 37904711
DOI: 10.1002/iid3.1041 -
Steroids May 2024Drug release from hyperbranched Janus dendrimer-drug conjugates and their subsequent activity are influenced by the different drugs in each dendron and the linker. To...
Drug release from hyperbranched Janus dendrimer-drug conjugates and their subsequent activity are influenced by the different drugs in each dendron and the linker. To understand these effects, we synthetized new Janus-type dendrimers of first and second generation. One dendron with 2,2-Bis(hydroxymethyl)propionic acid functionalized with ibuprofen and the second dendron was obtained with 3-aminopropanol-amidoamine and prednisone. The dendrimers were obtained by copper(I)-catalyzed Click azide-alkyne cycloaddition for the formation of a triazole as a dendrimeric nucleus of Janus dendrimer conjugates are reported. The influence of ibuprofen, prednisone, and spacer on cancer activity of Janus dendrimers conjugates is reported. The IC values of the anticancer activity on cancer cell lines the Janus dendrimer of second generation was higher in comparison to the first generation dendrimer. Similarly, the anticancer activity was higher compared to the dendron conjugates. Also, no cytotoxic effects of dendrons and dendrimers on non-cancerous kidney COS-7 cell line was observed. The interesting anticancer activity of the prepared prednisone-ibuprofen Janus dendrimer conjugates suggest that the dendrimers could be of potential use as new anticancer drug.
Topics: Anthracenes; Antineoplastic Agents; Dendrimers; Ibuprofen; Prednisone; Copper
PubMed: 38461962
DOI: 10.1016/j.steroids.2024.109395 -
Journal of the European Academy of... Feb 2024There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is... (Review)
Review
There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence-based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk-of-bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H and/ or H -antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state-of-the-art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well-designed, high-quality interventional trials are needed to establish evidence-based treatment guidelines for AU.
PubMed: 38420865
DOI: 10.1111/jdv.19904 -
RMD Open Apr 2024To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA).
METHODS
We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia.
RESULTS
31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes.
CONCLUSIONS
In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.
Topics: Humans; Arthritis, Rheumatoid; Prednisone; Hyperglycemia; Male; Female; Middle Aged; Diabetes Mellitus; Severity of Illness Index; Aged; Blood Glucose; Adult; Antirheumatic Agents; Risk Factors
PubMed: 38688692
DOI: 10.1136/rmdopen-2024-004246