Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab.

ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, or progressive disease, or intolerance with conventional HLH treatments. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. In total, 46 patients met the pHLH classification criteria. Median age at diagnosis was 1.0 year (range, 0.3-21.0). Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15 of 46 patients were in the intensive care unit, and 35 of 46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (24/33, 72.7%), ferritin (20/45, 44.4%), fibrinogen (37/38, 97.4%), platelets (39/46, 84.8%), and absolute neutrophil count (40/45, 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pretransplant survival was 38 of 42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant, and 23 of 31 (74.2%) of those who received transplant were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.

Gaining Consensus Around Patient Risk Groups and Prognostic Profiles to Guide CMV Management Among Patients With Allogeneic Hematopoietic Stem Cell Transplant: Insights From a Delphi Panel With Hematopoietic Stem Cell Transplant Experts.

INTRODUCTION: This study aimed to characterize patient risk groups and prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with allogeneic hematopoietic stem cell transplant (HSCT). METHODS: Between 8/2021 and 2/2022, a 3-round modified Delphi study was conducted to generate consensus among 10 international experts in HSCT and infectious diseases. Experts were asked about treatment and prognoses for patients in 7 distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top 2 options and ≥75% of experts were within 1 SD of mean ranks. RESULTS: Experts agreed on several unmet needs in CMV disease management post-HSCT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and the emergence of both refractory and drug-resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed a lack of long-term use data, concerns over potential resistance, high cost, and limited availability as challenges restricting adoption and successful patient management. CONCLUSIONS: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in patients with HSCT.

Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.

Gaining consensus around patient risk groups and prognostic profiles to guide CMV management among patients with solid organ transplant: Insights from a Delphi panel with SOT experts.

INTRODUCTION: This study aimed to characterize patient risk groups and respective prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with solid organ transplant (SOT). METHODS: Between September 2021 and February 2022, a three-round modified Delphi study was conducted to generate consensus among 14 international experts in virology and organ transplantation. Experts were asked about treatment and prognoses for patients in seven distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top two options and ≥75% of experts were within 1 standard deviation of the mean rank. RESULTS: Experts agreed on several unmet needs in CMV disease management post-SOT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and emergence of both primary refractory and drug resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed lack of long-term use data, concerns over potential resistance, high cost and limited availability as challenges restricting adoption, and successful patient management. CONCLUSION: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in SOT patients, but additional experiences with newer anti-CMV agents are needed to re-validate expert consensus and update post-transplant CMV guidelines.

Schizophrenia population health management: perspectives of and lessons learned from population health decision makers.

BACKGROUND: Despite therapeutic advances for patients with schizophrenia, improving patient outcomes and reducing the cost of care continue to challenge formulary decision makers. OBJECTIVES: To (1) understand the perspectives of formulary decision makers on challenges to optimal schizophrenia population management and (2) identify best practices and recommendations for mitigating these challenges. METHODS: This mixed-methods study, conducted in a double-blind manner, comprised in-depth telephone interviews with formulary decision makers from February through May 2020, and a web-based follow-on survey that was sent to all participants in October 2020. US-based formulary decision makers were recruited if they were directly involved in schizophrenia drug formulary or coverage decision making for national or regional payers, health systems, or behavioral health centers. Formulary decision makers' perceptions of challenges, policies, and programs related to schizophrenia population health management were assessed generally and in the context of the COVID-19 pandemic. RESULTS: 19 formulary decision makers participated in the interviews and 18 (95%) completed the survey. Participants reported a spectrum of patient- and payer-driven challenges in schizophrenia population health management, including medication nonadherence, high pharmacy and medical costs, and frequent hospitalizations and emergency department visits. Participants noted that COVID-19 had worsened all identified challenges, although patient unemployment (mean score of 2.00 on a scale of 1 [made much worse] to 5 [made much better]) and reduced access to psychiatric care (mean score, 2.12) were most negatively affected. The most common strategies implemented in order to improve schizophrenia population health management included case management (89%), telemedicine (83%), care coordination programs (72%), strategies to mitigate barriers to accessing medication (61%), and providing nonmedical services to address social determinants of health (56%). Participants noted that, ideally, all treatments for schizophrenia would be available on their formularies without utilization management policies in place in order to increase accessibility to medication, but cost to the health plans made that difficult. Whereas 61% of respondents believed that long-acting injectable antipsychotics (LAIs) were currently underused in their organizations, only 28% represented organizations with open access policies for LAIs. Participants believed that among patients with schizophrenia, LAIs were most beneficial for those with a history of poor or uncertain adherence to oral medications (mean score of 4.50 on a scale of 1 [not at all beneficial] to 5 [extremely beneficial]) and those with recurring emergency department visits and inpatient stays (mean score, 3.94). Study participants reported slightly increased use of LAIs (mean score of 3.17 on a scale of 1 [negatively impacted] to 5 [positively impacted]) among their patients with schizophrenia in response to the COVID-19 pandemic; 29% of participants reported easing access restrictions for LAIs. CONCLUSIONS: Participants described persisting challenges and various approaches intended to improve schizophrenia population health management. They also recommended strategies to optimize future health management for this population, including expanding programs to address social determinants of health and mitigating barriers to accessing treatment. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Roach, Graf, Pednekar, and Chou are employees of PRECISIONheor, which received financial support from Janssen Scientific Affairs, LLC, to conduct this study. Chou owns equity in Precision Medicine Group, the parent company of PRECISIONheor. Lin and Benson are employees of Janssen Scientific Affairs, LLC. Doshi has served as a consultant, advisory board member, or both, for Acadia, Allergan, Boehringer Ingelheim, Janssen, Merck, Otsuka, and Sage Therapeutics and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, Merck, Pfizer, PhRMA, Regeneron, Sanofi, and Valeant.

A Delphi Consensus Approach for Difficult-to-Treat Patients with Severe Hemophilia A without Inhibitors.

INTRODUCTION: Over the past decade, there has been an increase in novel therapeutic options to treat hemophilia A. It is still unclear how these novel treatments are used in the management of patients with hemophilia A, particularly those with challenging clinical scenarios who are typically excluded in clinical trials. PURPOSE: This study aimed to understand the areas of consensus and disagreement among hematologists regarding the preferences toward therapeutic approaches for difficult-to-treat patients with severe hemophilia A without inhibitors. PATIENTS AND METHODS: During February-June 2020, a three-round modified Delphi study was conducted to generate consensus among 13 US experts in the field of hemophilia. Experts were asked about their preferences toward therapeutic options for patients with challenging clinical situations, including age-related morbidities (eg, myocardial infarction, joint arthropathy), increasing demand for high-impact physical activities, early onset osteoporosis, and newborns with hemophilia A. Consensus was defined as ≥75% agreement between the panelists. RESULTS: Consensus was reached on many, but not all cases, leaving uncertainty about appropriateness of therapeutic approaches for some patients where clinical evidence is not available or driven by physicians' or patients' preferences toward therapeutic options. A majority of panelists preferred FVIII replacement therapy rather than emicizumab prophylaxis for the challenging cases presented due to established evidence on safety, efficacy, and level of bleed protection for FVIII treatment. CONCLUSION: Recommendations emerging from this study may help guide practicing hematologists in the management of challenging hemophilia A cases. Future studies are needed to address treatment options in the clinical cases where no consensus was reached.

Understanding the evolution of coverage policies for prophylaxis treatments of hemophilia A without inhibitors: a payer Delphi panel.

BACKGROUND: The landscape for hemophilia A prophylaxis is rapidly expanding from factor VIII replacement therapy to include novel treatments such as nonfactor replacement therapies that may enhance coagulation (e.g., emicizumab) or inhibit anticoagulant pathways (e.g., fitusiran and concizumab). For payers, this expansion presents challenges in balancing well-established treatments with new options that cost more and have lesser known real-world safety and efficacy. OBJECTIVE: To evaluate likely coverage practices for hemophilia A prophylaxis therapies among U.S. payers given evolving real-world data on safety and efficacy. METHODS: A 3-round modified Delphi process was conducted with representatives of U.S. commercial health plans who had considerable expertise in managing populations of patients with hemophilia. Round 1 consisted of an online questionnaire; round 2 involved an online discussion about the aggregated results from round 1; and round 3 allowed participants to revise their responses from round 1 based on insights gained during round 2. Questions elicited ratings, rankings, and estimates on access restrictions based on given safety and efficacy information for hemophilia A prophylaxis therapies. Consensus was reached if ≥ 74% of panelists (14 of 19) were within 1 SD of the median group estimate during round 3. RESULTS: 19 Payers participated in the research. Among them, 94% dealt with commercial insurance, 94% with Medicare, and 81% with Medicaid; 79% had spent ≥ 5 years in their current role. Panelists reported limited access restrictions on hemophilia A prophylaxis therapies; the most common restrictions were prior authorization (n = 16, 84%) and quantity level limits (n = 13, 67%). Tiering and step therapy were reported by 7 respondents (39%). Respondents agreed that there was an 80% median likelihood that ≥ 9 additional patients with any safety event (e.g., thrombotic event, death) per year would trigger access restrictions, with the median likelihood of restrictions increasing to 95% for another ≥ 10 patients with safety events per year. Respondents also agreed that > 5 thrombotic events requiring treatment per patient per year would have a 98% median likelihood of leading to access restrictions and that ≥ 5 years of real-world safety and efficacy data would be highly likely (95% median likelihood) to affect coverage decisions. Noncoverage was highly unlikely (ranked fifth or sixth of 6 by 14 respondents), as was no restriction-coverage parity (ranked sixth of 6 by 10 respondents). All else being equal, cost continues to affect access policies, with respondents agreeing that a 13%-30% difference in net cost may lead to preferred formulary treatment for a drug with superior efficacy and noninferior safety, inferior efficacy and noninferior safety, or noninferior efficacy and inferior safety. CONCLUSIONS: Payers prefer treatments with well-understood efficacy, safety, and cost over newer treatments with uncertain long-term effects. Relatively unrestricted access to legacy and new hemophilia A prophylaxis will likely continue unless additional real-world safety concerns or major cost differences emerge. DISCLOSURES: Financial support for this study was provided by Takeda Pharmaceutical Company, which was involved in study concept and design. Graf, Tuly, Harley, and Pednekar are employees of PRECISIONheor, a research consultancy to the health and life sciences industries that was contracted by Takeda to conduct this study and write the manuscript. Batt served as a consultant on this project through PRECISIONheor.

For which diseases do broader value elements matter most? An evaluation across 20 ICER evidence reports.

BACKGROUND: U.S. value framework developers such as the Institute for Clinical and Economic Review (ICER) use cost-effectiveness analysis to value new health care technologies. Often, these value assessment frameworks use a health system perspective without fully accounting for societal and broader benefits and costs of an intervention. Although there is ongoing debate about the most appropriate methods for including broader value elements in value assessment, it remains unclear whether the inclusion of these value elements is likely to affect the quantitative estimates of treatment value. OBJECTIVE: To assess variations in the relevance of broader value elements to cost-effectiveness analysis across diseases. METHODS: Thirty-two broader value elements (e.g., caregiver burden, health equity, real option value, productivity) not traditionally included in health technology assessments were identified through a targeted literature review. Evidence reports published by ICER between July 2017 and January 2020 were evaluated to identify which broader value elements were discussed as relevant to each disease in the report text. The study examined whether there were associations among ICER's discussion of broader value elements, rare disease status, treatment cost, estimated treatment cost-effectiveness, and ICER committee voting results for contextual considerations and additional benefits/disadvantages. RESULTS: The most commonly cited broader value element category in the ICER evidence reports was household and leisure (e.g., absenteeism from normal activities and caregiver burden). More value elements were cited for inherited retinal disease (19 elements) and sickle cell disease (18 elements) than for other diseases. Cardiovascular disease and diabetes had the fewest number of value elements cited (7 elements). Rare diseases were more likely to have broader value elements cited compared with nonrare diseases (15.9 vs. 11.5, P < 0.001). Treatments with higher (i.e., less favorable) incremental cost-effectiveness ratios were more likely to have a greater number of broader value elements cited (ρ = 0.625, P < 0.001). CONCLUSIONS: The presence of broader value elements varied across diseases, with less cost-effective treatments more likely to have a higher number of relevant broader value elements. Inclusion of all relevant value elements in value assessments will more appropriately incentivize innovation and improve allocation of research funding. DISCLOSURES: This study was sponsored by Novartis Pharmaceutical Corporation. At the time of this study, Shafrin was employed by PRECISIONheor, a consultancy to the life sciences industry that received financial support from Novartis to conduct this study. Dennen, Pednekar, and Birch are employed by PRECISIONheor. Bhor was an employee of Novartis Pharmaceutical Corporation at the time this research was conducted and manuscript was developed and reports grants from Novartis, unrelated to this work. Kanter has served on scientific advisory boards and steering committees for and reports receiving consulting fees from Novartis Pharmaceutical Corporation and is a site principal investigator on studies funded by Novartis Pharmaceutical Corporation. Kantar also reports support from Sickle Cell Disease Association of America Inc. and National Heart, Lung, and Blood Institute, unrelated to this work. Neumann reports advisory boards or consulting fees from Novartis Pharmaceutical Corporation and PRECISIONheor, as well as advisory boards or consulting fees unrelated to this study from AbbVie, Amgen, Avexis, Bayer, Congressional Budget Office, Janssen, Merck, Novartis, Novo Nordisk, Precision Health Economics, Veritech, Vertex; funding from The CEA Registry Sponsors by various pharmaceutical and medical device companies; and grants from Amgen, Lundbeck, Bill and Melinda Gates Foundation, National Pharmaceutical Council, Alzheimer's Association, and the National Institutes for Health.

Association of Medication Adherence with Hospital Utilization and Costs Among Elderly with Diabetes Enrolled in a State Pharmaceutical Assistance Program.

BACKGROUND: Medication adherence is crucial for the successful treatment among elderly patients with diabetes taking oral antidiabetic medications (OAMs). Cost of medications, lack of insurance coverage, and low income are major contributing factors towards medication nonadherence. State pharmaceutical assistance programs (SPAPs) provide medications at little or no cost to income-eligible patients and have potential to improve medication adherence among elderly patients. Despite this, limited research has focused on the association of medication adherence with health care utilization among elderly patients enrolled in SPAPs, and inclusion of health care costs as an outcome is even rarer. OBJECTIVE: To evaluate the relationship between adherence to OAMs and hospital utilization and costs among elderly patients with diabetes who were enrolled in a SPAP. METHODS: This retrospective observational study included elderly patients with diabetes enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program in 2015. Medication adherence was estimated as the proportion of days covered (PDC; adherent: PDC≥80%, nonadherent: PDC < 80%). Hospital utilization and costs were estimated using hospital discharge records from the Pennsylvania Health Care Cost Containment Council. Multiple adjusted regression analyses were used to examine the association of medication adherence with hospital utilization (all-cause and diabetes-related number of inpatient hospital visits and length of stay [LOS]) and costs. RESULTS: Among 9,497 elderly PACE enrollees with diabetes, 81% were adherent, and 21% were hospitalized. Compared with adherent patients, patients who were nonadherent to OAMs had twice the odds of all-cause and diabetes-related hospitalization. Controlling for covariates, nonadherent patients had 27% more all-cause (95% CI = 9%-36%) and 21% more diabetes-related (95% CI = 5%-40%) hospital visits than adherent patients. Covariate-adjusted LOS for nonadherent patients was 24% longer than that of adherent patients for all-cause hospitalization (95% CI = 1.171-1.311) and 12.7% longer for diabetes-related hospitalization (95% CI = 1.036-1.227). Medication nonadherence was associated with significantly greater all-cause ($22,670 vs. $16,383; P < 0.0001) and diabetes-related ($13,518 vs. $12,634; P = 0.0003) hospitalization costs. CONCLUSIONS: Among SPAP-enrolled elderly patients, nonadherence to OAMs was significantly associated with increased risk of hospitalization, longer hospital stays, and greater hospitalization costs. Attention is needed to improve medication adherence among elderly receiving financial assistance to pay their prescriptions to reduce economic burden on the health care system. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Mapping pharmacy deserts and determining accessibility to community pharmacy services for elderly enrolled in a State Pharmaceutical Assistance Program.

OBJECTIVES: Limited studies have investigated geographic accessibility to a nearby community pharmacy for elderly which is an essential determinant of the access to medications and pharmacy services. This research identified pharmacy deserts and investigated availability of different types of community pharmacies and their services for elderly enrolled in a State Pharmaceutical Assistance Program (SPAP). METHODS: The state of Pennsylvania in the US was used as a case to demonstrate the geographic accessibility to community pharmacy and services for elderly enrolled in SPAP. The locations of community pharmacies and households of elderly enrolled in SPAP were derived from Pharmaceutical Assistance Contract for the Elderly programs' database. The street addresses were geocoded and the distance to a nearby community pharmacy was calculated for study sample using the haversine formula. The demographic and geographic data were aggregated to Census Tracts and pharmacy deserts were identified using the predefined criteria. Descriptive statistical analysis was used to determine whether there are statistical differences in the socio-demographic profiles and distribution of different types of community pharmacies and their services in pharmacy deserts and non-deserts. This research used hot spot analyses at county level to identify clusters of pharmacy deserts, areas with high concentration of different racial/ethnic groups and clusters of high densities of chain and independent pharmacies. RESULTS: The Spatial analysis revealed that 39% and 61% Census Tracts in Pennsylvania were pharmacy deserts and non-deserts respectively (p < 0.001). Pharmacy deserts were found to have significantly more females, married and white elderly and fewer blacks and Hispanics compared to pharmacy non-deserts. Pharmacy deserts had significantly fewer chain and independent pharmacies and less delivery and 24-hour services in pharmacies than pharmacy non-deserts. Hot spot analyses showed that clusters of pharmacy deserts were more concentrated in southcentral, northwest and northeast regions of the state which represent rural areas and overlapped with clusters of high concentration of white individuals. CONCLUSIONS: The findings suggest that urban-rural inequality, racial/ethnic disparity and differences in availability of pharmacies and their services exist between pharmacy deserts and non-deserts. The methodological approach and analyses used in this study can also be applied to other public health programs to evaluate the coverage and breadth of public health services.

Cyclodextrin-based nanosponges: a propitious platform for enhancing drug delivery.

INTRODUCTION: Recently, Nanotechnology is receiving considerable acknowledgment due to its potential to combine features that are difficult to achieve by making use of a drug alone. Cyclodextrin-based nanosponges are yet another contemporary approach for highlighting the advancements which could be brought about in a drug delivery system. Statistical analyses have shown that around 40% of currently marketed drugs and about 90% of drugs in their developmental phase encounter solubility-related problems. Cyclodextrin-based nanosponges have the capacity to emerge as a productive approach over conventional cyclodextrins by overcoming the disadvantages associated with the latter. AREAS COVERED: This review is intended to give an insight regarding cyclodextrin-based nanosponges such as their physical and chemical properties. In addition, methods of preparation and characterization are discussed along with biocompatibility, and how these nanomeric elements can be exploited in developing effective drug formulations. EXPERT OPINION: This emerging technology of cyclodextrin-based nanosponges is expected to provide technical solutions to the formulation arena and to come up with some successful products in the pharmaceutical market. It also has an exciting future in the field of therapeutics wherein it can cater site-directed drug delivery and hence it possesses vibrant opportunities.

Aptamer-dendrimer bioconjugate: a nanotool for therapeutics, diagnosis, and imaging.

INTRODUCTION: Aptamers hold great promise as molecular tool in biomedical applications due to the therapeutic utility exhibited by their target specificity and sensitivity. Although current development of aptamer is hindered by its probable in vivo degradation, inefficient immobilization on probe surface, and generation of low detection signal, bioconjugation with nanomaterials can feasibly solve these problems. Nanostructures such as dendrimers, with multivalency and nonimmunogenicity, bioconjugated with aptamers have opened newer vistas for better pharmaceutical applications of aptamers. AREAS COVERED: This review covers brief overview of aptamers and dendrimers, with specific focus on recent progresses of aptamer-dendrimer (Apt-D) bioconjugate in areas of targeted drug delivery, diagnosis, and molecular imaging along with the discussion on the currently available conjugates, using their in vitro and in vivo results. EXPERT OPINION: The novel Apt-D bioconjugates have led to advances in targeting cancer cell, have amplified biosensing, and offered in vivo cell imaging. Because of the unique properties and applications, Apt-D bioconjugate propose an exciting future. However, further research in synthesis of new target-specific aptamers and their conjugation with dendrimers is required to establish full potential of Apt-D bioconjugate.