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Blood Aug 2020Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N = 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P = .068) and met the prespecified 1-sided α of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P = .0177), as did minimal residual disease (MRD) negativity (10-5 threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P < .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD34+ cell yield was 8.2 × 106/kg for D-RVd and 9.4 × 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT02874742.
Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Combined Modality Therapy; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Maintenance Chemotherapy; Male; Middle Aged; Multiple Myeloma; Patient Selection; Transplantation, Autologous
PubMed: 32325490
DOI: 10.1182/blood.2020005288 -
Gut Feb 2023There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.
DESIGN
We searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.
RESULTS
We identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).
CONCLUSION
In a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.
Topics: Humans; Crohn Disease; Adalimumab; Infliximab; Network Meta-Analysis; Biological Therapy; Remission Induction
PubMed: 35907636
DOI: 10.1136/gutjnl-2022-328052 -
American Family Physician Oct 2019Acne vulgaris is the most prevalent chronic skin disease in the United States, affecting nearly 50 million people per year, mostly adolescents and young adults....
Acne vulgaris is the most prevalent chronic skin disease in the United States, affecting nearly 50 million people per year, mostly adolescents and young adults. Potential sequelae of acne, such as scarring, dyspigmentation, and low self-esteem, may result in significant morbidity. Typical acne lesions involve the pilosebaceous follicles and the interrelated processes of sebum production, Cutibacterium acnes (previously called Propionibacterium acnes) colonization, and inflammation. Acne may be classified as mild, moderate, or severe based on the number and type of skin lesions. Multiple treatment agents and formulations are available, with each agent targeting a specific area within acne pathogenesis. Treatment selection is based on disease severity, patient preference, and tolerability. Topical retinoids are indicated for acne of any severity and for maintenance therapy. Systemic and topical antibiotics should be used only in combination with benzoyl peroxide and retinoids and for a maximum of 12 weeks. Isotretinoin is used for severe, recalcitrant acne. Because of the risk of teratogenicity, patients, pharmacists, and prescribers must register with the U.S. Food and Drug Administration-mandated risk management program, iPledge, before implementing isotretinoin therapy. There is limited evidence for physical modalities (e.g., laser therapy, light therapy, chemical peels) and complementary therapies (e.g., purified bee venom, low-glycemic-load diet, tea tree oil); therefore, further study is required.
Topics: Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Benzoyl Peroxide; Chronic Disease; Complementary Therapies; Curriculum; Dermatologic Agents; Education, Medical, Continuing; Female; Humans; Isotretinoin; Laser Therapy; Male; Phototherapy; United States; Young Adult
PubMed: 31613567
DOI: No ID Found -
The Journal of Clinical Endocrinology... Jun 2021Obesity is a chronic disease that is difficult to manage without holistic therapy. The therapeutic armamentarium for obesity primarily consists of 4 forms of therapy:... (Review)
Review
CONTEXT
Obesity is a chronic disease that is difficult to manage without holistic therapy. The therapeutic armamentarium for obesity primarily consists of 4 forms of therapy: lifestyle modification (ie, diet and exercise), cognitive behavioral therapy, pharmacotherapy, and bariatric surgery.
EVIDENCE ACQUISITION
Evidence was consolidated from randomized controlled trials, observational studies, and meta-analyses.
EVIDENCE SYNTHESIS
After 2 years, lifestyle interventions can facilitate weight loss that equates to ~5%. Even though lifestyle interventions are plagued by weight regain, they can have substantial effects on type 2 diabetes and cardiovascular disease risk. Although 10-year percentage excess weight loss can surpass 50% after bariatric surgery, weight regain is likely. To mitigate weight regain, instituting a multifactorial maintenance program is imperative. Such a program can integrate diet, exercise, and pharmacotherapy. Moreover, behavioral therapy can complement a maintenance program well.
CONCLUSIONS
Obesity is best managed by a multidisciplinary clinical team that integrates diet, exercise, and pharmacotherapy. Bariatric surgery is needed to manage type 2 diabetes and obesity in select patients.
Topics: Anti-Obesity Agents; Bariatric Surgery; Behavior Therapy; Diet, Reducing; Humans; Life Style; Meta-Analysis as Topic; Obesity; Obesity Management; Observational Studies as Topic; Randomized Controlled Trials as Topic; Time; Treatment Outcome
PubMed: 33595666
DOI: 10.1210/clinem/dgab091 -
Bioscience Trends Jul 2021The preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of... (Review)
Review
The preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of patients with liver cancer in China are already in the middle to advanced stage of the disease and no longer have the opportunity to undergo surgery. The goal of conversion therapy is to transform unresectable advanced liver cancer or potentially resectable liver cancer into resectable cancer, so it has become a topic of interest in the treatment of advanced liver cancer. Common modalities of conversion therapy are: local treatment (TACE, TARE, or HAIC), systemic treatment (targeted therapy alone or combined with immunotherapy), and a therapeutic alliance (TACE combined with radiation therapy, TACE combined with targeted therapy, HAIC combined with targeted therapy, or HAIC combined with targeted therapy and immunotherapy). The plan for maintenance treatment after conversion therapy is determined based on the outcome of conversion therapy to obtain the best survival benefit for patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; China; Hepatectomy; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Survival Rate; Treatment Outcome
PubMed: 34039818
DOI: 10.5582/bst.2021.01091 -
Journal of Clinical Oncology : Official... Jan 2023In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a and/or (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting.
METHODS
This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up.
RESULTS
The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; = .0004 [ < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups.
CONCLUSION
Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.
Topics: Female; Humans; Antineoplastic Agents; Follow-Up Studies; Maintenance Chemotherapy; Mutation; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phthalazines; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 36082969
DOI: 10.1200/JCO.22.01549 -
Bipolar Disorders Feb 2023Bipolar disorders are clinically complex, chronic and recurrent disorders. Few treatment options are effective across hypomanic, manic, depressive and mixed states and... (Review)
Review
AIMS
Bipolar disorders are clinically complex, chronic and recurrent disorders. Few treatment options are effective across hypomanic, manic, depressive and mixed states and as continuation or maintenance treatment after initial symptom remission. The aim of this review was to provide an up-to-date overview of research on the efficacy, tolerability and cognitive effects of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), deep brain stimulation (DBS) and vagus nerve stimulation (VNS).
METHODS
References included in this review were identified through multiple searches of the Embase, PubMed/MEDLINE and APA PsycINFO electronic databases for articles published from inception until February 2022. Published reviews, meta-analyses, randomised controlled trials and recent studies were prioritised to provide a comprehensive and up-to-date overview of research on brain stimulation in patients with bipolar disorders.
RESULTS
The evidence base for brain stimulation as an add-on or alternative to pharmacological and psychological treatments in patients with bipolar disorders is limited but rapidly expanding. Brain stimulation treatments represent an opportunity to treat all bipolar disorder states, including cognitive dysfunction during euthymic periods.
CONCLUSION
Whilst findings to date have been encouraging, larger randomised controlled trials with long-term follow-up are needed to clarify important questions regarding treatment efficacy and tolerability, the frequency of treatment-emergent affective switches and effects on cognitive function.
Topics: Humans; Bipolar Disorder; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Electroconvulsive Therapy; Treatment Outcome; Vagus Nerve Stimulation; Brain
PubMed: 36515461
DOI: 10.1111/bdi.13283 -
Nature Reviews. Immunology May 2023Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites... (Review)
Review
Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites and the venom of stinging insects. The classical protocol, introduced in 1911, involves repeated subcutaneous injection of increasing amounts of allergen extract, followed by maintenance injections over a period of 3 years, achieving a form of allergen-specific tolerance that provides clinical benefit for years after its discontinuation. More recently, administration through the sublingual route has emerged as an effective, safe alternative. Oral immunotherapy for peanut allergy induces effective 'desensitization' but not long-term tolerance. Research and clinical trials over the past few decades have elucidated the mechanisms underlying immunotherapy-induced tolerance, involving a reduction of allergen-specific T helper 2 (T2) cells, an induction of regulatory T and B cells, and production of IgG and IgA 'blocking' antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the T2 cell pathway.
Topics: Humans; Hypersensitivity; Desensitization, Immunologic; Allergens; Administration, Sublingual; B-Lymphocytes
PubMed: 36253555
DOI: 10.1038/s41577-022-00786-1 -
Annals of Nutrition & Metabolism 2021Dietary interventions as a first-line treatment for patients with polycystic ovary syndrome (PCOS) have been evaluated, but the optimal diet has not been determined.... (Review)
Review
BACKGROUND
Dietary interventions as a first-line treatment for patients with polycystic ovary syndrome (PCOS) have been evaluated, but the optimal diet has not been determined. Proper diet and the maintenance of adequate nutritional status are of great importance in the prevention of this disorder, and therapeutics and dietary habits play an important role in the recovery of patients with PCOS.
SUMMARY
A range of dietary patterns have been shown to impact weight loss and insulin resistance (IR) and improve reproductive function, including the Mediterranean diet, the ketogenic diet, Dietary Approaches to Stop Hypertension, and other dietary patterns. Key Messages: Diets that can reduce rates of obesity and IR are beneficial to women with PCOS, the status of obesity and IR should be determined at the early stage of the disease, so as to develop individualized and sustainable dietary intervention. The long-term efficacy, safety, and health benefits of diet management in patients with PCOS need to be tested by further researches.
Topics: Diet, Mediterranean; Female; Humans; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Weight Loss
PubMed: 34610596
DOI: 10.1159/000519302 -
Haematologica Sep 2023The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these... (Review)
Review
The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effective measures to prevent relapse are needed. There is also a need for post-HSCT maintenance to reduce relapse in high-risk subsets. Over the last 3 decades maintenance therapy in AML has evolved from the use of chemotherapeutic agents to more targeted therapies and better modulation of the immune system. Unfortunately, improvements in survival outcomes as a result of using these agents have not been consistently demonstrated in clinical trials. To derive the optimum benefit from maintenance therapy the time points of therapy initiation need to be defined and therapy must be selected precisely with respect to the AML genetics and risk stratification, prior treatment exposure, transplant eligibility, expected toxicity and the patient's clinical profile and desires. The far-reaching goal is to facilitate patients with AML in remission to achieve a normal quality of life while improving remission duration and overall survival. The QUAZAR trial was a welcome step towards a safe maintenance drug that is easy to administer and showed survival benefit but leaves many open issues for discussion. In this review we will discuss these issues, highlighting the development of AML maintenance therapies over the last 3 decades.
Topics: Humans; Quality of Life; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Recurrence
PubMed: 37139599
DOI: 10.3324/haematol.2022.281810