Kaitlynn Ely

Rituximab induction therapy has the highest probability of cost effectiveness in treating newly diagnosed patients with asymptomatic advanced follicular lymphoma, according to a study published in the 

The researchers estimated the cost-effectiveness of an active treatment strategy with rituximab to watchful waiting. While a previous study analyzed treatment choices in the Canadian health care system, this is the first known UK model that investigates treatment approaches.

Patients included in the study had asymptomatic follicular lymphoma and were deciding between active treatment utilizing rituximab or watchful waiting. If a patient experienced a relapse after active treatment, then he or she would be given another chemotherapy regimen with or without rituximab or an autologous transplantation. A randomized trial of the 3 treatment choices demonstrated no significant difference in survival rates.

Watchful waiting, rituximab induction, and maintenance costs were estimated using dosages and unit costs from the British National Formulary (BNF). Patients who chose watchful waiting—54%&mdash;required new treatment within 3 years. Patients treated with rituximab induction had an 11% chance of needing continued treatment after 3 years, while 19% of patients who received induction with rituximab followed by maintenance needed new treatment after 3 years. Annual recurrence rates were converted to 22.8%, 6.7% and 3.9%, respectively.

At follow-up visits, patients underwent physical examinations in which clinicians assessed symptoms and performed tests, such as a full blood count, liver and renal function assessment, and immunoglobin profile. Patients who experienced a recurrence were generally treated with immunochemotherapy. Costs for these tests and procedures were sourced from the National Health Service Reference costs.

Quality of life was measured based on an unpublished Oxford Outcomes study used in the National Institute for Health and Care Excellence (NICE) technology. The researchers assumed that there was no quality of life benefit for patients using watchful waiting compared to rituximab treatment, as it is potentially beneficial to treat the disease than wait for symptoms to arise.

The data show that rituximab induction alone is the most cost-effective approach in treating asymptomatic follicular lymphoma. While treatment outcome was improved when induction of rituximab was paired with rituximab maintenance, the value of the treatment was worth less than the cost. Watchful waiting was deemed the least cost-effective approach in treating advanced follicular lymphoma.

Some study limitations that the authors noted include the uncertainty around treatment in subsequent therapy lines, the unpublished quality of the life study on which researchers formed their model, and the unmeasured cost of possible reduced immunoglobulin levels in a patient when treated with rituximab.

“The results of the base case analysis suggest that rituximab induction alone is the most cost-effective strategy to adopt in patients with asymptomatic follicular lymphoma,” the 

. “This result was shown to be robust in [1]-way and probabilistic sensitivity analyses.”

Prettyjohns M, Hoskin P, McNamara C, et al. The cost&#8208;effectiveness of immediate treatment or watch and wait with deferred chemotherapy for advanced asymptomatic follicular lymphoma. 

. 2018;180(1):52-59. doi: 10.1111/bjh.14990.

Articles

Rituximab induction therapy has the highest probability of cost effectiveness in treating newly diagnosed patients with asymptomatic advanced follicular lymphoma, according to a study published in the British Journal of Haematology.
 

Rituximab Induction Is Cost Effective for Asymptomatic Advanced Follicular Lymphoma

A noninvasive evaluation determining the severity of inflammatory bowel disease (IBD) and the treatment efficacy of infliximab is made possible by locating universal biomarkers in human fecal microbiota, according to a study 

 by the American Society for Microbiology's 

An increase in industrialization across the world has caused an increase of IBD among populations in less developed regions; ulcerative colitis (UC) and Crohn disease (CD) are the 2 main clinical types of IBD, with global incidence of these diseases on the rise.

The etiology of these conditions is not well understood; however, past research has suggested that an imbalance of gut microbiota may be the main cause of IBD. In the literature, IBD patients when compared to healthy individuals have a reduced biodiversity, a decreased abundance of several taxa in the 

In the study, researchers profiled the fecal microbiota from a cohort of Chinese patients with IBD, then compared the results to 2 western IBD cohorts by using bar-coded 165 rRNA amplicon sequencing. IBD patients included in the study were also compared to healthy western and Chinese individuals. This was a multicenter association study in which over 1000 treatment-naïve patients participated.

The goals of the study were to locate the microbiota patterns in Chinese IBD patients with different disease activities, discover different gut microbiota patterns across ethnicities and geographic locations, and to recognize any universal biomarkers across the IBD cohorts that could indicate and predict disease progression and infliximab treatment efficacy.

1,376,142 rRNA gene sequences were taken from 196 samples. A microbial imbalance of gut microbiota patterns was found in Chinese IBD patients. In addition, researchers recognized that the sequencing of gut microbiota in Chinese IBD patients was similar to those of the western cohorts. Researchers also saw gut microbiota being restored during disease remission while certain microbes, like 

, displayed the body’s response to infliximab treatment of CD.

In patients with IBD, it was found that gut microbial levels lack in diversity. After receiving infliximab treatment, CD patients restored their microbial diversity and increased their 

 reduced proinflammatory bacteria, produced short-chain fatty acids, and induced an immune response.

“Our results reinforce the idea that the gut microbiota contains promising biomarkers for the noninvasive evaluation of IBD activity and assessment of therapeutic responses,” the authors concluded. “The identification of [a] disease-activity associated microbiome is a step toward establishing a set of microbiota-based biomarkers for the assessment of treatment and progression of inflammatory bowel disease.”

Zhou Y, Xu ZZ, He Y, et al. Gut microbiota offers universal biomarkers across ethnicity in inflammatory bowel disease diagnosis and infliximab response prediction. mSystems. 2018;3(1):e00188-17. doi: 10.1128/mSystems.00188-17.

In patients with IBD, it was found that gut microbial levels lack in diversity. After receiving infliximab treatment, CD patients restored their microbial diversity and increased their Clostridiales levels. Clostridiales reduced proinflammatory bacteria, produced short-chain fatty acids, and induced an immune response.
 

Noninvasive Evaluation Can Help Determine Infliximab's Efficacy in IBD

One week after intravitreal bevacizumab injection, corneal endothelial cells showed no sign of inflammation or any other complications, according to a 

Corneal endothelial cells make up the structure of the cornea and are located at the innermost layer. An increase in intraocular pressure (IOP) can cause corneal scarring and damage the endothelial cells, leading to significant loss of vision. If these cells are damaged, it is impossible to regenerate them.

The risks of a high IOP include the function of the endothelial pump, induced corneal edema and hypoxia, and reduced intraocular blood flow.

While some injections in the cornea can lead to increased IOP, therapeutic intravitreal bevacizumab injections increase IOP for just 30 minutes, followed by a drop to normal levels. The study analyzed the momentary changes and safety of corneal endothelial cells and corneal thickness once there is an acute increase resulting from the injection.

At Dankook University Hospital in South Korea, 42 eyes (in 42 patients) were included in the study. These eyes were treated with intravitreal bevacizumab injections to treat macula edema or macular degeneration between May 2014 and January 2015. Before each injection was completed, patients took a benchmark exam that gave baseline visual acuity and optical coherence tomography, a slit-lamp examination, and a fundus examination. In addition, IOP and endothelial cell evaluations were conducted before and after injection. Two measurements were made in the cornea to assess the density of endothelial cells (CD) and the central corneal thickness (CTT). The mean IOP was calculated by taking 3 measurements from the eye.

The results showed that there was a significant increase in IOP from baseline in all patients. Before the injection, mean IOP was 11.48 and significantly increased from 49.71 mmHg at 2 minutes to 37.64 mmHg 5 minutes after the injection. After 30 minutes, IOP returned to a normal range. After 1 week, there was no sign of inflammation in any of the 42 study participants.

There was no significant correlation in changes of CTT and CD to an increase in IOP pressure. The researchers believe that further analysis of a larger sample population is needed to measure the changing patterns of corneal endothelial cells during and after intravitreal bevacizumab injection.

“When bevacizumab is intravitreally injected, an acute increase of IOP occurs, but after 30 [minutes], the IOP normalized,” the authors wrote. “During this process, endothelial cells may receive momentary compression and stretch pressure, but it is tolerable and has no harmful effects on the corneal endothelium.”

Park J, Lee M. Short-term effects and safety of an acute increase of intraocular pressure after intravitreal bevacizumab injection on corneal endothelial cells. 

 2018;18(1):17. doi: 10.1186/s12886-018-0682-9.

One week after intravitreal bevacizumab injection, corneal endothelial cells showed no sign of inflammation or any other complications, according to a study published in BMC Ophthalmology.

IOP Increases, Then Decreases Within 30 Minutes of Intravitreal Bevacizumab Injection

Patients with rheumatoid arthritis (RA) who use corticosteroids can delay the initiation of biologic disease-modifying antirheumatic drugs (DMARDs), have higher incidence of adverse events (AEs), and have more healthcare costs before the initiation of biologic DMARDs than patients who do not use corticosteroids, according to a 

Patients with RA often use corticosteroids to quickly relieve pain or swelling. 

 recommends low doses as a short-term therapy (up to 3 months) until patients can feel the benefits of DMARDs, due to adverse events related to long-term corticosteroid use, including weight gain, worsened diabetes, and increased risk of infection.

The researchers in this study used a retrospective analysis to measure patterns of corticosteroid use, the duration of use, and the dosage amount. Utilizing the Cox proportional hazards models, the effects of corticosteroid use on the amount of time it took to initiate DMARDs was also evaluated. In addition, the researchers analyzed the probability of AEs due to corticosteroid use.

25,542 patients with RA were included in the analysis. The mean patient age was 53.55 years, and over 70% of patients were female. Nearly 10% of these patients used corticosteroids for a long period of time (over 3 months). Most of these patients were older, more likely to be female, lived in the US South, were treated by a rheumatologist, and most importantly, had more comorbidities.

Corticosteroid users compared to non-users had significantly higher incidence rates of cardiovascular events, gastrointestinal events, infections, skin events, lipodystrophy, metabolic and endocrinologic events, neuropsychiatric events, and ophthalmologic events. They also had higher average health care costs compared to nonusers. Patients who used corticosteroids for longer durations at lower dosages were less likely to initiate biologic DMARDs.

The authors found that health care providers who prescribe corticosteroids for a longer period of time may not want to disrupt treatment by waiting for DMARDs to have an effect. It is recommended that physicians limit patient use of corticosteroids, as they delay early initiation of biologic DMARDs, which are associated with improved outcomes and decreased hospitalization.

“This study thus provides evidence that corticosteroid utilization may have deleterious effects on RA patient health and may increase the cost burden associated with treatment,” the authors concluded. “Future studies should continue to examine the appropriate and optimal use of corticosteroids and biologic DMARDs in RA treatment.”

Spivery CA, Griffith J, Kaplan C, Postlethwaite A, Ganguli A, Wang J. Published December 4, 2017. 

Patients with rheumatoid arthritis (RA) who use corticosteroids can delay the initiation of biologic disease-modifying antirheumatic drugs (DMARDs), have higher incidence of adverse events (AEs), and have more healthcare costs before the initiation of biologic DMARDs than patients who do not use corticosteroids.

Study: Corticosteroid Use May Delay Initiation of Biologics in Patients With RA

Managed care professionals can assist ophthalmologists and retina specialists in personalizing anti-vascular endothelial growth factor (anti-VEGF) treatment to encourage patient adherence, according to a recent 

Journal of Managed Care & Specialty Pharmacy

Neovascular age-related macular degeneration (nAMD) remains a leading cause of blindness in the United States despite the introduction of 3 FDA-approved anti-VEGF drugs. Aflibercept and ranibizumab are 2 therapies that treat nAMD, while bevacizumab, a therapy for oncology indications, is increasingly used off-label in treating nAMD.

Despite the proven efficacy in clinical trials of all 3 treatments, there are significant challenges in administering the therapies in a real-world setting that many studies fail to note: these include delays in diagnosis and treatment approval, patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring.

In 1 study, over the period of 1 year, visual acuity (VA) scores, which measure the ability of the eye to distinguish details and shapes at a distance, on specialized charts, and the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, increased significantly among patients who were administered ranibizumab.

The CATT trial compared outcomes of ranibizumab and bevacizumab when administered monthly or as needed. In a year, mean VA scores increased by a range of 5.9 letters in the bevacizumab cohort and 8.5 letters in the ranibizumab cohort.

The VIEW 1 and VIEW 2 trials were designed to compare ranibizumab to aflibercept. Patients with nAMD were randomly assigned doses of ranibizumab or aflibercept every 4 weeks or every 8 weeks. The results showed that there were no significant differences in outcomes between the 2 different dosing intervals of the drug.

The cost of managing nAMD can range from $65,000 to over $250,000 over 20 years. Previous studies have found bevacizumab to be more cost-effective than the other therapies. However, age, general health, and anatomic characteristics (including presence of retinal fluid leakage, hemorrhage, and fibrotic scarring) are all factors that underscore the importance of managing nAMD treatment on an individual level.

Patients are not likely to adhere to nAMD treatment due to fears of having injections in the eye, anticipating pain, or discomfort. Other determinants of health may be age-related (for example, difficulty arranging and traveling to appointments for treatment).

Retina specialists have responded to the burdens and high costs of anti-VEGF treatment by developing alternative regimens based on extended fixed intervals, as needed based on disease activity, and/or by a treat-and-extend strategy.

Managed care organizations can increase public awareness surrounding the condition through educational programs and resources. This can incentivize patients to modify lifestyle behaviors and reduce risks.

“The efficacy of anti-VEGF therapy for nAMD has been consistently demonstrated in clinical trials; however, real-world gaps and challenges can pose significant barriers to achieving treatment goals,” the authors concluded. “In collaboration with ophthalmologists and retina specialists, managed care professionals can play key roles in overcoming barriers associated with underdiagnosis of nAMD, delays between [choroidal neovascularization, CNV] growth and anti-VEGF treatment initiation, lack of awareness about AMD among the public, and the logistic, emotional, and financial burdens of frequent intravitreal injections.”

Managed care professionals can assist ophthalmologists and retina specialists in personalizing anti-vascular endothelial growth factor (anti-VEGF) treatment to encourage patient adherence, according to a recent review of the literature on this topic.

Kaitlynn Ely

Rituximab Induction Is Cost Effective for Asymptomatic Advanced Follicular Lymphoma

Noninvasive Evaluation Can Help Determine Infliximab's Efficacy in IBD

IOP Increases, Then Decreases Within 30 Minutes of Intravitreal Bevacizumab Injection

Study: Corticosteroid Use May Delay Initiation of Biologics in Patients With RA

Personalized Anti-VEGF Regimens Improve Adherence Among Patients With Macular Degeneration