Advances in Therapy最新文献

The multiple sclerosis (MS) treatment landscape has expanded over time, becoming increasingly complex with the availability of more advanced high-efficacy therapies (HETs). In this evolving context, shared decision-making (SDM) between healthcare providers (HCPs) and patients is crucial for optimizing treatment and ensuring personalized care. Cladribine tablets (CladT), a highly effective therapy with a well-established safety profile, are approved in the USA for treating adults with relapsing MS, including those aged ≥ 50 years. Globally, more than 89,000 patients have received CladT. HCPs have considered transitioning patients from HETs, such as anti-CD20 monoclonal antibodies, to CladT. Further research is needed to understand factors influencing the decision to switch from an anti-CD20 therapy to CladT. This podcast explores real-world insights and challenges from USA-based advanced practice providers who have switched patients with MS from anti-CD20 therapies to CladT. The discussion builds on the results from a real-world retrospective survey of 100 HCPs aimed at understanding their rationale for transitioning patients from anti-CD20 therapies (e.g., ocrelizumab, ofatumumab, rituximab, ublituximab) to CladT. The survey also assessed differences in rationale for discontinuing anti-CD20 therapies and switching from anti-CD20 therapies to CladT between patients aged < 50 and ≥ 50 years. Findings revealed that the most common reasons for transitioning from anti-CD20 therapy to CladT included perception of increased efficacy on relapses (55%) and disability progression (54%), while common reasons for discontinuing anti-CD20 therapy included relapses (41%) and continued clinical activity (26%). In patients aged > 50 years, desire to avoid long-term immunosuppression (45%) was a key factor in choosing CladT after anti-CD20 therapy. Notably, AEs suggestive of immunosuppression or opportunistic infections were not reported in patients who transitioned to CladT, and no new safety signals, infections, or immunoglobulin reductions were observed. This podcast also highlights the economic benefits of CladT, the role of SDM, and recommendations based on clinical experiences.

Introduction

Lifelong antiretroviral therapy (ART) persistence prevents the progression of human immunodeficiency virus (HIV)-related illnesses and reduces HIV transmission. People with HIV who have a mental health disorder or substance use disorder (PWH-MHD/SUD) often face persistence challenges. This real-world study compared ART persistence among PWH-MHD/SUD who restarted various ART regimens after a treatment interruption.

Methods

This observational, retrospective cohort study analyzed US claims data from the HealthVerity Marketplace from January 2015 through February 2024. PWH aged ≥ 18 years who restarted the same ART regimen they had previously discontinued for > 90 days were included. The population of PWH-MHD/SUD was analyzed. Pairwise comparisons were conducted for those who received bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) versus dolutegravir (DTG)/lamivudine (3TC), DTG/abacavir (ABC)/3TC, and DTG-based multitablet regimens [MTRs; i.e., DTG + F/TAF or DTG + F/tenofovir disoproxil fumarate (TDF)]. Baseline characteristics were balanced using inverse probability of treatment weighting. Time to nonpersistence (i.e., ART regimen discontinuation or switching) was depicted using Kaplan–Meier plots. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using weighted Cox proportional hazards models.

Results

Among all the PWH who restarted a previously discontinued ART regimen (n = 20,623), 43.4% had an MHD or SUD. Compared with PWH-MHD/SUD who received B/F/TAF, those receiving DTG/ABC/3TC and DTG-based MTRs were significantly more likely to be nonpersistent [weighted HR (95% CI) 1.18 (1.09–1.29) and 1.19 (1.06–1.34), respectively], while there was no significant difference for those receiving DTG/3TC. Compared with those receiving B/F/TAF, the risk of switching was significantly higher for PWH-MHD/SUD receiving DTG/3TC, DTG/ABC/3TC, or a DTG-based MTR [weighted HR (95% CI) 1.68 (1.08–2.63), 2.67 (2.23–3.19), and 2.88 (2.32–3.58), respectively]. These results were generally consistent among the broader population of restarters.

Conclusion

For PWH-MHD/SUD who restarted ART after a treatment interruption, B/F/TAF was associated with longer persistence and the lowest risk of switch compared with other guideline-recommended therapies.

Introduction

The study objective was to determine the value contribution of palopegteriparatide to the treatment of adults with chronic hypoparathyroidism, a rare endocrine disease, through a multi-criteria decision analysis (MCDA).

Methods

The Orphar-SEFH group framework for evaluating orphan drugs was used, along with the weighting performed by 98 national and regional evaluators. A multidisciplinary panel of seven experts individually scored the evidence matrix. The scores were collected and analysed using Microsoft Excel software programmed for MCDA study analysis. The results were discussed in a reflective discussion session.

Results

The expert panel considered chronic hypoparathyroidism to be a moderate-to-severe disease (mean ± SD: 3.3 ± 0.5) due to its multiorgan impact and associated comorbidities, with significant unmet needs (3.6 ± 1.0), particularly related to the lack of the physiological effect due to insufficient levels of parathyroid hormone. The experts found palopegteriparatide as an add-on treatment to conventional therapy (calcium and active vitamin D) to be much more effective than placebo plus conventional therapy, with this criterion receiving the highest score. The safety profile was considered acceptable (1.6 ± 1.1). The participants highlighted the positive impact of palopegteriparatide on patient-reported outcomes (2.9 ± 0.9) compared to placebo because of improvements in quality of life (QoL). Palopegteriparatide was seen as a potentially disease-modifying treatment, which could lead to savings in "other medical costs" (3.1 ± 1.1) and "non-medical/indirect costs" (2.0 ± 0.8), although no evidence was available, especially in the long term. The quality of the evidence was perceived as high (3.6 ± 0.5). The overall value contribution of palopegteriparatide was 0.58 (+ 1 = maximum value) compared to placebo. The study has some limitations, including a relatively small panel size and the exclusion of treatment cost as a criterion due to lack of pricing information at the time of evaluation.

Conclusion

According to MCDA, palopegteriparatide represents a valuable therapeutic option for chronic hypoparathyroidism treatment, particularly due to its demonstrated efficacy, which had an impact on patients’ QoL, and the current unmet needs in this therapeutic area.

Clinical trials investigating asthma therapies typically rely on pulmonary function tests including spirometry markers, such as forced expiratory volume in 1 s, to evaluate efficacy. While these measures provide insights into the action of bronchodilators on global lung function, their specific effects on the airways and the relationship between clinical improvements and airway dysfunction remains poorly understood. In recent years, pulmonary functional imaging methods, such as hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI), have enabled the analysis of airway dysfunction in patients with asthma utilizing ventilation defect percent (VDP). In this narrative review, we summarize clinical evidence about the impact of inhaled bronchodilator therapies on airway dysfunction in patients with asthma, focusing on studies that utilized ¹²⁹Xe MRI to visualize and quantify MRI VDP. ¹²⁹Xe MRI VDP has been shown to be a well-tolerated and sensitive technique for enabling the visualization and quantification of airway functional changes over time in patients with asthma. This has been shown not only in a controlled clinical trial environment but also in a real-world setting, in patients with both controlled and poorly controlled asthma. A recent study evaluating single-inhaler triple therapy in patients with uncontrolled moderate–severe asthma, despite inhaled corticosteroid/long-acting β₂-agonist maintenance therapy, demonstrated that daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 200/62.5/25 µg) led to significantly improved ¹²⁹Xe MRI VDP after only 6 weeks, which was in line with broader central/distal airway function and quality of life improvements. These results highlight the capacity of ¹²⁹Xe MRI VDP to detect early responses to treatment. In addition, the mechanistic insights provided by ¹²⁹Xe MRI VDP also indicated that these benefits are likely due to the combination of UMEC (a long-acting muscarinic antagonist) and an efficacious inhaled corticosteroid, addressing undertreated inflammatory bronchoconstriction, helping to restore airway caliber and function that more closely resemble the airways of a healthy individual.

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Introduction

Dienogest (DNG) is widely used to manage endometriosis-associated pain; however, long-term data comparing low and standard doses are limited. Therefore, this study aimed to evaluate the efficacy and safety of 48-week DNG treatment (1 mg/day vs. 2 mg/day) in patients with endometriosis-related dysmenorrhea (composite score).

Methods

In this randomized, open-label, parallel-group, trial, 88 patients with endometriosis were enrolled, all of whom had at least one ovarian endometriotic cyst confirmed by imaging. Other phenotypes of endometriosis, such as deep infiltrating or peritoneal lesions, were not systematically assessed and may have been present. Patients were randomized to receive either 1-mg/day or 2-mg/day DNG. The primary endpoint was the change in menstrual pain measured using a visual analog scale (VAS). Secondary endpoints included changes in the dysmenorrhea score, ovarian endometrioma volume, serum estradiol levels, bone mineral density (BMD), and menopausal symptoms.

Results

Both groups demonstrated a significant reduction in menstrual pain (VAS). The mean VAS scores decreased by 44.63 and 54.19 mm in the 1-mg and 2-mg groups, respectively. However, the between-group difference (– 9.57 mm; 95% confidence interval: − 22.7 to 3.56) was not above the predefined non-inferiority margin of – 15 mm; thus, non-inferiority of the 1-mg dose could not be confirmed. Improvements in dysmenorrhea scores and endometrioma volume were also observed in both groups, although greater effects were noted in the 2-mg group than in the 1-mg group. Serum estradiol suppression was comparable between the groups, whereas BMD loss was less pronounced in the 1-mg group than in the 2-mg group.

Conclusions

This study did not demonstrate statistical non-inferiority of 1-mg/day DNG treatment over 2-mg/day DNG treatment for pain relief. These results suggest that the 2-mg/day dose may offer more robust analgesic effects, particularly during the early treatment phase. However, 1-mg/day DNG still showed meaningful symptom improvement with fewer adverse events than 2-mg/day DNG, supporting its potential use in selected patients requiring long-term therapy.

Trial Registration Japan Registry of Clinical Trials, trial registration number: jRCTs041210016.

Introduction

Historically, anxiety and depression rates have been higher among individuals with myasthenia gravis (MG) than the general population, and self-reported sentiments and experiences of mental health impairment may be more common than formal diagnoses. Patient-centered research can provide insight into self-described anxiety and depressive symptoms and stressors experienced by those with MG in the United States (US) and improve understanding of the current prevalence of anxiety and depression.

Methods

Insights were collected from three sources. First, a literature review of quantitative and/or real-world studies of anxiety/depression among individuals with gMG in the US. Second, a secondary, qualitative analysis of the transcripts from focus groups conducted with 12 individuals with self-reported generalized MG. Third, analysis of thousands of online conversations between people with self-reported ocular or generalized MG using search, data extraction, and artificial intelligence-powered algorithms. No statistical analyses were performed.

Results

The literature review identified three studies (precluding a meta-analysis): prevalence estimates for depression were 19% (diagnosed), 31% (receiving antidepressants), and 75% (self-reported sentiments), and for anxiety were 17%, 19% (both diagnosed), and 82% (self-reported sentiments). Unique stressors and triggers were identified, classified into four categories: experience of symptoms/uncontrolled symptoms; burden of medical care; daily life functioning, responsibilities, and aspirations; and social support needs. The relative prominence of each stressor and its induced emotion varied by stage in the disease journey: fear and anxiety were discussed more frequently prior to MG diagnosis, whereas hopelessness and depression became more prominent later, during ongoing disease monitoring and management. Patients felt that stress worsened symptoms in a positive feedback loop.

Conclusion

This qualitative, hypothesis-generating study found that individuals with MG in the US were more likely to report experiencing anxiety and depression than the general population due, at least in part, to their MG-specific disease journey and the uncontrolled symptoms experienced.

Introduction

Type 2 diabetes (T2D) is a chronic metabolic disease that is highly prevalent in the United Arab Emirates (UAE). This study aimed to assess the cost-consequences of adding gliclazide modified release (MR) to metformin in patients with inadequate glycaemic control on metformin alone and of switching patients currently receiving a combination of sitagliptin and metformin to a combination of gliclazide MR and metformin.

Methods

We developed a cost-consequences decision-tree model comparing gliclazide MR and sitagliptin as second-line add-ons to metformin. Based on 2014–2023 Dubai Real World Claims Database data, the model estimated health outcomes (number of patients reaching HbA_1c targets of < 7% and ≤ 6.5% and cardiovascular [CV] events, i.e. myocardial infarction [MI] and hospitalisation for heart failure [HHF]), resource use (inpatient, emergency room, and outpatient visits, and hospital bed days), and costs (drug acquisition and medical costs) associated with the two therapies over a 1-year time horizon from the payer perspective.

Results

Adding gliclazide MR to metformin in a cohort of 126,074 patients with inadequate glycaemic control on metformin alone was estimated to result in 535 CV events and 35 deaths avoided per year at a cost of USD 12,250 per CV event avoided or USD 189,415 per death avoided. Switching patients currently treated with sitagliptin as an add-on to metformin to gliclazide MR was estimated to avert 26 cardiovascular events (5 MI and 21 HHF) and 2 deaths per year while providing annual savings of USD 5.11 million, including USD 4.77 million in drug acquisition costs and USD 330,837 in medical costs.

Conclusion

Initiating gliclazide MR as an add-on treatment to metformin could help to reduce the clinical and economic burden of poorly controlled T2D among patients in the UAE. Switching patients from sitagliptin to gliclazide MR as a second-line treatment option could generate substantial cost savings.