Advances in Therapy最新文献

Endometriosis is a common disease, affecting approximately 5–10% of reproductively aged women. Symptoms, such as painful periods, negatively impact an individual’s quality of life; however, these symptoms are often normalized, leading to delays in diagnosis and treatment, and worsening of the disease. In this podcast, a reproductive endocrinologist (Dr Sanjay K Agarwal) and patient advocate (Tara Mangum) provide their perspectives on the diagnosis and management of endometriosis. They also discuss Relugolix combination therapy as a treatment option for patients with endometriosis.

Podcast available for this article.

Background

While patients with cancer have traditionally received oncology treatments through intravenous (IV) administration, some therapies are becoming available via alternative modes of administration, such as subcutaneous (SC). This study aimed to evaluate IV versus SC therapy administration from the perspectives of the patient, healthcare provider (HCP), and healthcare system.

Methods

A systematic review was conducted, searching MEDLINE and Embase databases from 2000 to 2022. This was supplemented with grey literature searches of additional sources such as conference proceedings. Observational studies and clinical trials were included if they assessed adult patients with any cancer type who were treated with pharmacologic therapies administered via IV or SC and included patient- or HCP-reported outcomes or healthcare system perspectives on the mode of administration. Records identified by the literature search were screened by two independent reviewers. Included studies were data extracted by a single reviewer and validated by a second reviewer and synthesized using a narrative approach.

Results

After screening, 33 unique studies were included in the systematic review. Patients and HCPs reported substantially more favorable preference rates for SC over IV treatment. Additionally, from the patient perspective there were reductions in treatment time and economic burden for SC compared with IV therapy. From the HCP’s perspective, treatment time was consistently reduced by SC compared with IV treatment administration. Although information on the impact of SC and IV treatments for oncology on healthcare systems was limited, the use of SC formulations showed consistent cost savings (direct costs) and time savings from this perspective considering various uptake scenarios compared with IV administration.

Conclusion

Compared with IV administration, SC oncology treatment is a preferred option by patients and HCPs, increasing optionality and reducing treatment time while simultaneously increasing capacity and reducing the financial burden on healthcare systems.

Introduction

In Japan, patients with chronic obstructive pulmonary disease (COPD) can be escalated to treatment with inhaled triple therapy. Two single-inhaler triple therapies combining an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β₂-agonist (ICS/LAMA/LABA) are approved maintenance therapies for patients with COPD, and multiple-inhaler triple therapies (MITTs) are also available. There is limited evidence regarding real-life treatment patterns and characteristics of patients with COPD initiating triple therapies.

Methods

This observational, retrospective cohort study identified patients with COPD in Japan from an administrative claims database (May 2018–December 2021). Demographics, clinical characteristics, and healthcare resource utilization (HCRU) were assessed in four cohorts initiating a triple therapy: budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) early adopters (initiated ≤ 12 months after market approval [September 1, 2019]), contemporary BGF users (initiated > 12 months after market approval), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) users, and any MITT users.

Results

A total of 636 patients were BGF early adopters, 2558 were contemporary BGF users, 11,187 used FF/UMEC/VI, and 5931 used MITT. The percentage of patients with concomitant asthma in each cohort was 73.0%, BGF early adopter; 74.2%, contemporary BGF; 75.7%, FF/UMEC/VI; and 84.5%, MITT. During the 12-month baseline period, the frequency of patients with ≥ 1 moderate/severe exacerbation was 18.2%, BGF early adopter; 14.3%, contemporary BGF; 13.1%, FF/UMEC/VI; and 14.0%, MITT. ICS/LABA treatment during baseline was the most frequent pathway to triple therapy, ranging from 38.2% to 51.7% across cohorts. HCRU was relatively high across cohorts (range of hospital outpatient visits/patient during the 12-month baseline period, 11.0–14.1). Multimorbidity was observed in > 80% of patients in all cohorts; cardiovascular diseases were among the most common.

Conclusion

Many patients initiating triple therapy for COPD had concomitant asthma and had previously received ICS/LABA maintenance therapy. Patients prescribed BGF in the initial post-launch period were more likely to have a previous exacerbation history versus other cohorts, indicating more severe disease.

Introduction

Veterans in the US have higher rates of lower extremity amputation (LEA) compared to the general population and these rates have increased between 2008 and 2018. There is limited data which directly evaluate the potential underlying comorbidities associated with LEA in the veterans’ population especially with the most recent data. Such information is critical to help inform clinical management strategies to reduce the risk of amputations among our veterans.

Methods

This was a retrospective observational study of adults in the Veterans Health Administration database who underwent LEA from January 1, 2019 to December 31, 2023. The date of the first LEA procedure was defined as the index date. Index LEA type, patient demographic at baseline, and clinical characteristics (including diagnoses for conditions associated with LEA and other comorbidities) 1 year before and 30 days after the index LEA procedure (except for bacterial infections which the identification period was 30 days before and 30 days after the index LEA procedure) were described.

Results

Of the 27,134 Veterans with LEA, 67.3% were ≥ 65 years of age, 97.0% were male, and 65.3% were non-Hispanic white. The most common type of LEA was transmetatarsal (52.9%), followed by toe (21.9%), above-knee (15.4%), and below-knee (9.8%). The most prevalent diagnoses associated with LEA were diabetes (81.6%), bacterial infections (79.1%), and peripheral artery disease (PAD; 63.3%). Only 15 Veterans (< 0.1%) had a diagnosis for combat-related injuries to lower extremities.

Conclusion

Diabetes and PAD are highly prevalent and among the main conditions associated with LEA among US Veterans. Earlier and more effective preventative and clinical management of these conditions offer an opportunity to significantly reduce the rates of LEA in this population.

Introduction

A systematic literature review and network meta-analysis was conducted on azilsartan medoxomil (AZL-M) versus other antihypertensive drugs’ efficacy in hypertensive patients.

Methods

The search utilized English platforms, from January 2000 until December 2023, resulting in 10,380 articles being screened. Screening criteria included hypertension (mild or moderate); first-line treatment and washout periods; studies (monotherapy) with AZL-M, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta-blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; and antihypertension efficacy as an outcome measure. Study design was randomized clinical trials. Efficacy variables included absolute office systolic and diastolic blood pressure (BP) reductions. A total of 21 publications provided adequate data for analysis, of which 20 studies reported both systolic and diastolic BP and one study reported only the diastolic BP.

Results

In 21 studies on systolic BP, against the common comparator placebo, the differences in systolic BP were significantly in favor of AZL-M, amlodipine, candesartan, irbesartan, nebivolol, nifedipine, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The surface under the cumulative ranking curve (SUCRA) ranking shows that AZL-M 80 mg had the highest ranking, with a possibility of 93% being the best in all other included treatments. In 20 studies on diastolic BP, against the common comparator placebo, the differences in diastolic BP were significantly in favor of AZL-M, amlodipine, bisoprolol, nebivolol, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The SUCRA ranking shows that AZL-M 80 mg had the highest ranking, with a possibility of 90% being the best in all other included treatments.

Conclusion

AZL-M at 40 mg and 80 mg shows favorable efficacy compared to other anti-hypertensives, and the 80 mg dosage seemed to be the most efficacious of all the included treatments in reducing both office systolic and diastolic BP in patients with mild-to-moderate hypertension.

Introduction

Short bowel syndrome (SBS) is associated with a significant mental and physical burden for patients and caregivers. Standard of care (SOC) for SBS includes parenteral support (PS) to optimize intestinal function. Teduglutide, a recombinant human glucagon-like peptide 2 analogue, reduces the need for PS in patients with SBS. In this study, we assessed the cost-effectiveness of teduglutide in pediatric patients with SBS from multiple perspectives, considering the caregiver’s burden.

Methods

A Markov model was used to evaluate cost (Japanese yen, JPY) and effectiveness (quality-adjusted life years, QALYs) of teduglutide compared with SOC for pediatric patients with SBS in Japan. We conducted a base-case analysis and selected sensitivity and scenario analyses from three perspectives: (1) the public healthcare payer, (2) the public healthcare and long-term care payer, and (3) society.

Results

In the base-case analysis, the incremental cost-effectiveness ratio (ICER) was 9,533,412 JPY per QALY from the public healthcare payer perspective, 6,335,980 JPY per QALY from the public healthcare and long-term care payer perspective, and 3,510,371 JPY per QALY from the societal perspective. The probability that cost-effectiveness of teduglutide is favorable from a societal perspective was 59.3%. In all scenario analyses, consistent with the base-case analysis, ICERs for teduglutide compared with SOC were different depending on whether caregiver utility and productivity loss were considered.

Conclusions

Incorporating the caregiver’s burden in the cost-effectiveness analysis of teduglutide for pediatric patients with SBS provided a more comprehensive assessment of the value of teduglutide for patients, their families, and society. This approach enhances our understanding of the overall value of a treatment, especially for diseases with significant caregiver burden.

Introduction

This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP).

Methods

In this open-label study (NCT05029622), Chinese children (girls < 9 years, boys < 10 years) received two doses of triptorelin pamoate 22.5 mg (day 1 and month 6). Primary endpoint was the proportion at month 6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5 IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline.

Results

Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5–9] years). At month 6, all patients had LH suppression; this was maintained at month 12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months 3 to 12 had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month 6 and 12, respectively; all boys had regression or stable genital development until month 12. Compared with baseline (9.82 cm/year), mean growth velocity was 5.88 cm/year at month 6 and 5.17 cm/year at month 12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month 6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month 6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported.

Conclusion

The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP.

Trial Registration

Trial registration: ClinicalTrials.gov identifier, NCT05029622.

Introduction

Behçet’s disease (BD) with intestinal, neurological (NBD), and vascular (VBD) manifestations often leads to poor outcomes. Infliximab is approved for the treatment of intestinal BD, NBD, and VBD in Japan; however, evidence regarding its safety and effectiveness in these patients is limited. We conducted a 2-year post-marketing surveillance to evaluate the safety and effectiveness of infliximab in patients with intestinal BD, NBD, and VBD in Japan.

Methods

This 2-year, multicenter, prospective, observational study included all patients with intestinal BD, NBD, or VBD, who had experienced an insufficient response to conventional therapies (e.g., glucocorticoids and immunosuppressants/immunomodulators), and initiated infliximab for the first time at participating medical institutions. The safety endpoints included adverse events and adverse drug reactions (ADRs), and the effectiveness endpoints included global improvement, and for patients with acute NBD, acute attacks.

Results

Between October 2015 and August 2018, 255 patients (171 intestinal BD, 49 NBD, and 51 VBD; including 16 with two disease types) were enrolled from 133 medical centers and treated with infliximab. Adverse events, ADRs, and serious ADRs occurred in 100 (39.2%), 72 (28.2%), and 38 (14.9%) patients, respectively; incidences were generally similar across intestinal BD, NBD, and VBD groups. No new safety concerns were identified. At the final evaluation, 68.8% of patients with intestinal BD showed improvement, most patients with chronic progressive NBD and VBD had not worsened (100% and 91.7%, respectively), and 93.3% of patients with acute NBD had no new acute attacks during the observation period.

Conclusion

These results confirmed the safety and effectiveness of infliximab in clinical practice in 255 patients with intestinal BD, NBD, and VBD. There were no new safety concerns.

Introduction

This study aimed to compare the efficacy and safety of biologics and small molecules for treatment of adults with moderately-to-severely active ulcerative colitis (UC).

Methods

A systematic literature review was conducted to identify randomised controlled trials evaluating approved and emerging targeted therapies for patients with UC. A Bayesian network meta-analysis (NMA) approach was applied. Outcomes assessed included clinical response and remission, endoscopic mucosal healing, and safety.

Results

Thirty studies were included in the NMA following a feasibility assessment comparing approved induction dosing regimens and 22 studies comparing approved maintenance dosing regimens. In the biologic/Janus kinase inhibitor (JAKi)-naïve population, induction studies showed similar clinical response and remission rates across most interventions, with upadacitinib demonstrating significant improvements versus most other interventions. For maintenance studies, mirikizumab demonstrated significant improvements in clinical response and remission versus most other interventions. In the biologic/JAKi-experienced population, no significant differences were observed between most interventions in induction studies, except for significantly improved clinical response and remission for mirikizumab versus adalimumab, and upadacitinib demonstrated significant improvement versus all other interventions. Few differences between active treatments were observed in maintenance studies. In both populations, all active interventions had similar efficacy in terms of endoscopic mucosal healing in both induction and maintenance studies. Regardless of prior treatment exposure, similar rates of serious adverse events were seen across all active interventions in the induction period.

Conclusion

Among the available interventions, owing to its favourable efficacy and safety profile, mirikizumab has a relevant role in the long-term treatment of UC.

Background

Biosimilars offer significant advantages for improving access to biologic treatments in Latin America. However, their uptake has been slow due to misconceptions, regulatory uncertainties, and inadequate pharmacovigilance.

Objective

To address these issues, Americas Health Foundation convened a multidisciplinary panel of regional experts in biosimilar use and interchangeability from Latin America. The panel assessed the current landscape and recommended steps to enhance access.

Results

Key recommendations include strengthening biosimilar regulations, ensuring transparent enforcement, implementing robust pharmacovigilance, and promoting collaboration among stakeholders to educate about the safety, efficacy, and economic advantages of biosimilars and their interchangeability.

Conclusions

By embracing biosimilars and interchangeability, Latin American countries can expand patient access, foster competition, diversify treatment sources, and enhance the sustainability of their healthcare systems. However, achieving these goals requires addressing knowledge gaps and biases among healthcare providers, patients, regulators, and government agencies. This can be accomplished through clear communication and the use of real-world evidence.