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Jeff Temple, PhD, licensed psychologist, vice dean for research, UTMB School of Nursing, discusses the rising mental health crisis in adolescents and strategies for community stakeholders to mitigate this issue with AJMC® Associate Editor Matthew Gavidia.

Take a DEEP DIVE Into Medical World News

AJMC Associate Editor Matthew Gavidia sat down with Shannon Burke, SVP and general manager of health systems at Synchrony Health & Wellness, to discuss the importance of exercise on her physical and mental health and how it has improved her productivity.

Find Out What Managed Care Experts Like to Do AFTER HOURS

Julia is an associate editor for The American Journal of Managed Care® (AJMC®) and joined AJMC® in 2022. She produces written and video content covering multiple disease states, and assists in the screening process for manuscripts submitted to AJMC®.

She has a BA in English language and literature from Rutgers University. You can connect with Julia on 

Posters presented at the American Academy of Ophthalmology 2022 annual meeting showed that an 8-year treat-and-extend (T&E) regimen was effective in managing visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD), making consistent adherence to treatment for older patients with nAMD vital to optimizing outcomes.

T&E regimens are commonly used for intravitreal antivascular endothelial growth factor (VEGF) treatment in patients with nAMD.

 evaluated 8-year VA outcomes after T&E treatment. In this  retrospective, interventional, single-center case center study, 165 treatment-naive eyes from 137 patients were evaluated. The eyes were treated with ranibizumab, aflibercept, bevacizumab, or brolucizumab for 1 or more years. The average best corrected visual acuity (BCVA) was 53 ETDRS letters.

The mean number of injections per patient from year 1 to year 8 were 7.9, 6.1, 5.8, 6.0, 6.2, 5.9, 6.2, and 6.0, respectively, with corresonding mean (SD) BCVA changes from baseline of 8.3 (21.8), 7.1 (25.0), 4.7 (26.5), 4.5 (27.1), 4.5 (28.3), 5.1 (26.5), –0.5 (34.8), and –4.3 (38.9) ETDRS letters. A total of 24.2% of the eyes lost at least 15 letters, 26.1% gained at least 15 letters, and 49.7% maintained vision within 15 letters by the final follow-up.

The researchers concluded that treatment with a T&E regimen was effective in maintaining VA in nAMD for 6 years of treatment. The seventh and eighth year saw a decline in ETDRS letters, but further data collection would be needed to confirm these findings.

 was focused on determining which patients with nAMD were most likely to be lost to follow-up, as consistent treatment is key to optimizing their outcomes and learning how to treat patients with nAMD.

The study used the IRIS Registry from the AAO to gather data on participants. Patients whose nAMD was diagnosed between January 1, 2013, and December 31, 2015, and treated with anti-VEGF therapy from January 1, 2013, to December 31, 2018, were included in the study. Patients with proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusion, myopic degeneration, and idiopathic choroidal neovascularization were excluded from this study.

Loss to follow-up was defined as patients not being seen for more than a year after their last intravitreal injection. A multivariable logistic regression analysis was used to determine the odds ratios (ORs) of each result.

A total of 191,694 patients were included in the analysis, 11% of whom were lost to follow-up. Age was a primary risk factor for loss to follow-up, as patients aged 76 to 80 years (OR, 1.20; 95% CI, 1.10-1.31), 81 to 85 years (OR, 1.48; 95% CI, 1.36-1.60), 86 to 90 years (OR, 2.05; 95% CI, 1.89-2.22), and older than 90 years (OR, 2.95; 95% CI, 2.72-3.19) were more likely to be lost to follow-up compared with patients younger than 70 years.

Women were found to be less likely to be lost to follow-up (OR, 0.82; 95% CI, 0.80-0.85) compared with men, and African American patients (OR, 1.28; 95% CI, 1.07-1.52) and Hispanic patients (OR, 1.20; 95% CI, 1.09-1.33) were more likely to be lost to follow-up compared with White patients.

Also more likely to be lost to follow-up were patients with unilateral disease (OR, 2.43; 95% CI, 2.30-2.57) vs those who were affected bilaterally and patients with Medicaid coverage (OR, 1.42; 95% CI, 1.17-1.74) vs private insurance. Patients with Medicare coverage were less likely to be lost to follow-up (OR, 0.73; 95% CI, 0.69-0.78) vs those with private insurance.

The researchers concluded there was a high rate of loss to follow-up in patients with nAMD who were treated with anti-VEGF injections, with the biggest risk factors of losing a patient to follow-up included age, male sex, African American and Hispanic ethnicity, unilateral disease, and Medicaid insurance. New strategies, they concluded, are needed to encourage better compliance and adherence to maximize outcomes in patients with nAMD.

These 2 posters combine to present a view of nAMD that encourages treatment and narrows down those who are most at risk for stopping treatment that would help their visual outcomes. Learning which treatments are the most effective in maintaining VA could help encourage those who are less likely to maintain treatment to stay on their treatment.

1. Fong RD, Thomas M, Romero C, et al. Eight-year VA outcomes of the T&E regimen in the management of nAMD. Presented at: AAO 2022; September 30, 2022-October 3, 2022; Chicago, IL. Abstract PO419.

2. Khurana RN, Li C, Lum F. Loss to follow-up in patients with nAMD treated with anti-VEGF therapy in the U.S. Presented at: AAO 2022; September 30, 2022-October 3, 2022; Chicago, IL. Abstract PO377.

Articles

Posters presented at the American Academy of Ophthalmology 2022 annual meeting show that the treat-and-extend (T&E) regimen was effective in managing neovascular age-related macular degeneration (nAMD), which makes adherence to treatment vital for long-term outcomes.

T&E Regimen, Consistent Adherence Important to Management of nAMD

Skylar is an associate editor for The American Journal of Managed Care® (AJMC®) and The Center for Biosimilars®, and joined AJMC® in 2020. She is responsible for covering all aspects of the ever-changing global biosimilar industry and produces content that is accessible and informative for all health care stakeholders.

She has a BA in journalism and media studies from Rutgers University. You can connect with Skylar on 

Michael F. Chiang, MD, director of the National Eye Institute (NEI), explained some of the current research the agency is conducting regarding the use of artificial intelligence (AI) and telemedicine in ophthalmology and why ophthalmologists should be paying attention.

What are some of the biggest actions that the National Eye Institute has taken recently that retinal specialists should be following?

What I would highlight—2 things that we've done at the National Eye Institute—that should be important to every single retina specialist.

Number 1 is imaging and data science. Within the past 20 years, there have been advances, things like OCT [optical coherence tomography] and artificial intelligence [AI] that are really changing the nature of retina practice, making it go from qualitative to quantitative. 

So, I think it's going to be important for every retina specialists to stay on top of that and to really think very hard about how you can use those technologies to become a better physician. How you can take advantage of them and use them in your practices. 

The other thing is, how to understand what those technologies do not do and how to cultivate those skills in yourself, like, for example, communication with patients. So, I think that those are the ways that retina practice is going to be changing. And so, definitely stay on top of that.

Another thing that I would highlight is that because imaging is so fundamental to retina practice—that's obvious—but the problem is that these imaging devices often don't talk to each other and they don't talk to electronic health records. That's a huge problem for clinical care and for research, and when these data are all locked in proprietary standards. At the NEI, we've been working really hard with the FDA and with the Office of National Coordinator for Health Care it because we regulate research and they're the bodies that regulate devices and data. We're really trying to address this problem. 

The good news is that the vendors really seem to want to do the right thing for the community. I think this is going to really make a big difference for clinical practice. And so just definitely keep that in mind. You know, these devices really need to talk to each other and there are going to be huge benefits of that.

What has been the NEI’s approach to telemedicine and AI for the purposes of diagnosing and treating ophthalmic conditions?

There's obviously been enormous work, especially in artificial intelligence in the past 5 years. My perspective, at the National Eye Institute, is that there's a lot of potential for that. But there's also risk. 

One of the risks is that many of these studies in AI are done in relatively narrow populations. And the problem is that our country is very broad. There's, men and women, different races, different populations. And what we really do not want to have is a world where AI systems work in one population but not in other populations. And so we're really, really trying to drive the fact that we've got to have broad validation and broad generalizability of these systems.

One program that we're really excited about is something that's called Bridge to AI. It is a trans–[National Institutes of Health] program, so it applies to every field. The premise is basically that we're spending $130 million over 4 years to support building data, data that are broad, diverse, and AI ready. 

And one thing that I'm really excited about is that we announced the recipients of these grants about 2 weeks ago. And of the 4 data generation sites that got funded, one of them is actually led by ophthalmologists Aaron Lee, MD, and Cecilia Lee, MD, at the University of Washington. I obviously think that there's so much about AI that ophthalmology can really contribute to. So, it's very exciting.

In terms of telemedicine. I think we all learned from this pandemic, that we're moving into a remote world. And so, I really think that what we need to do is to move away from studies that are framed around "Well, how can I get a CPT [Current Procedural Terminology] code for doing this service?" more toward studies that try to develop new models of remote care, that are based on telemedicine and data collection—Who's going to collect the data? Who's going to aggregate it? Who's going to look at it?—because I think that's really how we're going to advance the field and how we're going to use things like telemedicine to really address things like health disparities in this country by increasing accessibility to eye care.

Videos

Advances in imaging and data science are changing the nature of retina practice, and retina specialists need to stay on top of these, said Michael F. Chiang, MD, director of the National Eye Institute (NEI), who also discussed some of the current research the agency is conducting into artificial intelligence (AI) and telemedicine.

Dr Michael Chiang Chronicles the NEI's Research Into AI, Telemedicine in Ophthalmology

Maggie is an editor for The American Journal of Managed Care® (AJMC®) and produces written, video, and podcast content covering several disease states. She joined AJMC® in 2019, and has been with AJMC®’s parent company, MJH Life Sciences®, since 2014, when she started as a copy editor.

She has a BA in English from Penn State University. You can connect with Maggie on 

Mary is the associate editorial director for The American Journal of Managed Care® (AJMC®), The Center for Biosimilars®, and Evidence-Based Oncology™. She joined AJMC® in 2013 and oversees speaker recruitment and panel preparations for AJMC®'s premier annual oncology meeting, Patient-Centered Oncology Care®.

She has a BA in communications and philosophy from Loyola University New Orleans. You can connect with Mary on 

, Stephen M. Schleicher, MD, MBA, chief medical officer and medical oncologist, Tennessee Oncology, discusses the importance of a strong infrastructure comprising data analytics that can highlight care gaps for improvement, a culture primed for change and innovation, and invested teams that enabled some practices to see success with the Oncology Care Model (OCM).

Analyses of the OCM have found that overall, the model lost money, but some individual practices did well. What were the most important keys to success?

It’s interesting. Everybody talks about how the OCM failed, because it lost a lot of money across the country, but if you look at certain practices that really had the infrastructure and doubled down to do well, they did very successful in the OCM from a quality and cost standpoint, including Tennessee Oncology.

I think the framework was you’ve got to have the right culture for change and innovation, the right people, and the right teams, and then the analytics to know where the gaps are to improve quality and cost reduction and how to track that and hold people accountable, including the teams doing the work themselves. Those are kind of the 3 underlying themes that Tennessee Oncology doubled down on to succeed and that allowed us to do things like influence drug utilization, really change our care management strategy to keep people out of the emergency room in the hospital, really focus on palliative care, end-of-life care, and things like that.

But with the right culture, the right people, and the right analytics that was all possible.

Co-hosted by Memorial Sloan Kettering Cancer Center, the most recent Institute for Value-Based Medicine® event took place on September 22, with a focus on improving cancer care delivery through innovation.


Dr Stephen Schleicher: Culture, People, Analytics Contributed to OCM Success 

Michel Michaelides, MD, FACP, explains how gene therapy can be used to treat retinitis pigmentosa, an inherited eye disease, and how it could be used in the future of eye care. Michaelides is a consultant ophthalmologist at Moorfields Eye Hospital in the Department of Medical Retina, Inherited Eye Disease and Paediatric Ophthalmology and a professor of ophthalmology at the University College London Institute of Ophthalmology's Genetics Department.

 (GTPase regulator) gene as it pertains to retinitis pigmentosa and how can gene therapy address it?

Retinitis pigmentosa [RP] is genetically very variable with more than 100 different genes that cause RP. 

 is one of the more common causes of RP. It tends to be one of the more severe forms as well. So it's particularly meaningful that we are on the cusp of potentially having an approvable drug for RPGR. So, fingers crossed for the phase 3 study that is being undertaken currently.

How do you expect for gene therapy for the treatment of retinal diseases and other ophthalmic conditions to develop in the future?

So, I'm very optimistic....there have been a couple of studies that haven't quite achieved their primary end point recently, but I think that's to be expected in drug development. We have an approved therapy for one of our rarer conditions. And I'm certain there will be an increase in approved drugs over the next 5 years to really make a positive impact on our patients lives.

Gene therapy can be used to treat retinitis pigmentosa, an inherited eye disease, and there is likely to be an increase in approved gene therapies for ophthalmic conditions, explained Michel Michaelides, MD, FACP, a consultant ophthalmologist and a professor of ophthalmology at the University College London Institute of Ophthalmology's Genetics Department.

Dr Michel Michaelides Dives Into How Gene Therapy Can Treat Retinitis Pigmentosa

Study findings presented at a session at the 

 (AAO) 2022 conference in Chicago, Illinois, showed that outcomes in eyes treated for moderate vision loss due to center-involved diabetic macular edema (CI-DME) were similar over 2 years, whether the patients were treated first with aflibercept alone or with the administration of bevacizumab first plus a switch to aflibercept therapy.

Starting patients on bevacizumab before switching to aflibercept if there was a suboptimal response was safe and effective, the study found.

The study was presented by Chirag Jhaveri, MD, an affiliate faculty member in the Department of Ophthalmology at Dell Medical School at the University of Texas in Austin. The retina specialist is also vice chair for the Diabetic Retinopathy Clinical Research network (DRCR.net), which presented the research results Saturday. The study findings were published the 

A previous study by the same research group, Protocol T, found that eyes with a visual acuity (VA) of 20/50 or worse had better visual outcomes after aflibercept treatment through 2 years when compared with eyes treated with bevacizumab (mean improvement of 18.1 vs 13.3 ETDRS [Early Treatment of Diabetic Retinopathy Study] letters) and had better vision through 1 year compared with patients on ranibizumab.

Many patients with 20/50 vision or worse who were treated with bevacizumab had good visual outcomes as well, with 68% achieving a final VA of 20/40 or better after 2 years.

However, aflibercept and ranibizumab cost much more than bevacizumab—$1826 and $825 per dose, respectively, compared with $70 for bevacizumab.

The Saturday presentation focused on the Protocol AC trial, which looked at whether step therapy, where payers require the less expensive drug first, had an impact on visual outcomes. Did patients starting on bevacizumab and switching to aflibercept face compromises in their long-term VA compared with patients strictly on aflibercept monotherapy?

Bevacizumab is often more available and widely used outside of the United States, noted Jhaveri.

“Step therapy is where patients are forced to use a certain medication before the physician can use another medication usually secondary to cost,” he said. “And so in this situation, for example, bevacizumab, which is off-label, is often required for us to use before we have the opportunity to use aflibercept, which is on-label.”

The randomized multicenter clinical trial enrolled 312 eyes. Patients were included if they aged 18 years and older and had type 1 or type 2 diabetes. Patients needed to have vision of 20/50 or worse. They could have had previous anti–vascular endothelial growth factor (VEGF) injections but it could not have been within 12 months. Other treatments for DME could not have been taken within 4 months.

The patients were split into 2 groups, where 1 group had aflibercept alone and the other group was started on bevacizumab. Patients in the bevacizumab group could switch to aflibercept at and after 12 weeks if they had persistent CI-DME, had an injection with bevacizumab given at the last 2 visits, eye had not improved by at least 5 letters over the previous 2 visits, central subfield thickness (CST) had not improved by 10% or more over the past 2 visits, and vision was worse than 20/50 before 24 weeks had elapsed or 20/32 or worse 24 weeks or later.

“And the rationale for [switching medicine if patients had 20/32 vision or worse] is that maybe there were some patients who improved a little bit on bevacizumab first but plateaued. Could switching them to aflibercept allow for additional vision gains?” said Jhaveri.

Patients who were switched to aflibercept were given at least 2 injections before resuming treatment guidelines. There were 6 monthly injections, except for eyes where VA of 20/20 was achieved along with a CST less than the prespecified threshholds, as well as stable VA and CST.

There were 158 patients who started with aflibercept monotherapy and 154 who started with bevacizumab. Both groups were 48% female and the median age was 60 and 61 years respectively. White participants made up 52% and 54% of each respective group. Patients on bevacizumab had about 1 1/2 more injections on average compared with those on aflibercept. Baseline characteristics were similar in each group, with 16% and 19% of the groups having prior intravitreal anti-VEGF treatment for DME.

Most of the patients who had bevacizumab first (70%) met the switch criteria for aflibercept by the end of the 2-year period compared with 30% of the patients on aflibercept monotherapy.

VA after 2 years was similar in both groups as 22% of both groups had vision of 20/20 or better (adjusted difference, –1%; 95% CI, –11% to 8%); 73% of the aflibercept group and 74% of the bevacizumab-first group had VA of 20/40 or better (adjusted difference, –7%; 95% CI, –19% to 5%).

Only 5% of the aflibercept group and 2% of the bevacizumab first group had VA of 20/200 or worse (adjusted difference, 3%; 95% CI, –1% to 7%).

Although aflibercept performed better than bevacizumab within the first year of treatment, both medications performed similarly across 2 years, with CST reduced in both treatments. In the aflibercept group, 60% of the participants had resolved CI-DME compared with 55% of the bevacizumab group.

The study did not include any anti-VEGF agents other than aflibercept that were FDA-approved for treatment of DME, which was a significant limitation. Serious adverse events and hospitalizations for adverse events were more common in the aflibercept-only group.

“Initiating therapy with bevacizumab and switching to aflibercept that's done in this trial is a safe and effective alternative to aflibercept monotherapy in eyes with moderate vision loss due to center-involved DME,” said Jhaveri.

Given the 26-fold difference in cost between aflibercept and bevacizumab, the findings demonstrate the potential of significant cost savings, he said.

Jhaveri CD, Glassman AR, Ferris FL, et al; DRCR Retina Network. Aflibercept monotherapy or bevacizumab first for diabetic macular edema. 

2022;387:692-703. doi:10.1056/NEJMoa2204225

Allison Inserro contributed to this report.

The presentation focused on the Protocol AC trial, which considered whether step therapy had an impact on visual outcomes for patients starting on bevacizumab and switching to aflibercept later. 



Which DME Drug to Try First? Similar Outcomes of Aflibercept, Bevacizumab, but Different Costs

Rose is a freelance writer for The American Journal of Managed Care® (AJMC®), where she previously worked as an editor.

She has a BA in journalism & media studies and Spanish from Rutgers University. You can connect with Rose on 

Extramedullary hematopoiesis (EMH) is a rare complication of 

 (BT) that is more commonly seen in mild to moderate cases of BT. But a 

suggests that EMH is also a significant clinical complication in transfusion-dependent BT (TDT) and warrants prospective studies on optimal treatment strategies.

BT, a condition characterized by reduced production of the beta-globin chain of hemoglobin, is estimated to occur in up to 5% of the global population. Depending on clinical characteristics, BT can be stratified into 2 main types: thalassemia major (TM) and thalassemia intermedia (TI). Patients with TM typically depend on regular blood transfusions, whereas those with TI are non–transfusion dependent (NTDT). EMH, a rare complication of BT and other hematological conditions, occurs when blood cells develop in locations outside of the bone marrow in response to reduced production within the marrow. EMH is reported in up to 20% of patients with NTDT vs less than 1% of patients with TDT.

“Treatment options for thalassemia patients with EMH depend on the location and mass effect symptom, including hyper transfusion, surgical excision, radiotherapy, hydroxyurea, or various combinations of therapy,” the authors wrote. “The main aim of this review is to pool all the available data on the presentations and management of EMH in the context of TDT, providing summary statistics.”

A literature search returned 253 reported cases of EMH in patients with TM, encompassing 2 retrospective studies and 70 case reports. The mean age at EMH presentation was 35 years, and the spinal cord was the most commonly involved site of EMH (87.7% of cases).

Most cases (72%), including those in the retrospective studies, did not specify the presenting features. In cases that did report on presenting features, there was a wide range of clinical features and symptoms. The clinical features of spinal cord compression were seen in 32 patients, although this was a small number relative to the number of cases in which the spinal area was involved in EMH. The authors attribute this to the fact that patients in the retrospective studies (n = 182) did not have symptoms of EMH. Lower-limb weakness, pain at the site of EMH, and urinary incontinence were also reported (9%, 7.5%, and 1.18% of patients, respectively). Masses were found via examination or imaging in 4% of patients.

EMH was most commonly diagnosed by MRI (89.3% of cases), with CT scans showing 9.9% of cases. In 9 patients (3.6%), histopathological diagnosis was made. The most common treatment was blood transfusion to increase pretransfusion hemoglobin levels, followed by radiation therapy, surgery, hydroxyurea, and steroids.

Currently, there are no clear guidelines regarding EMH management in TDT, although conservative management through blood transfusions appears to be the preferred option for patients with mild or no symptoms. Achieving sufficient pretransfusion hemoglobin levels to avoid EMH is key, and clinicians should be aware of the risk of EMH in patients who do not reach optimal levels, the authors noted.

“We could not find any study comparing different therapeutic approaches and their outcomes in BTM patients who developed EMH. Our review found similar results (wherever outcomes were reported) with conservative and invasive methods,” the authors wrote. “Therefore, it is imperative to study the effects of the treatment options (non-invasive and invasive) prospectively so physicians may have clear guidelines based on the best treatment options.”

The lack of data on outcomes in the studies within the review prevented a statistical analysis of outcomes based on treatment strategy. However, the authors concluded that EMH represents an increasingly significant complication in TDT and warrants further research in this population.

A Subahi E, Ata F, Choudry H, et al. Extramedullary haematopoiesis in patients with transfusion dependent β-thalassaemia (TDT): a systematic review. 

. Published online March 9, 2022. doi:10.1080/07853890.2022.2048065

Currently, there are no clear guidelines for managing extramedullary hematopoiesis in transfusion-dependent beta thalassemia. 

Review: More Research on Treatment for Extramedullary Hematopoiesis in Transfusion-Dependent Beta Thalassemia Is Needed

Laura is the vice president of content for The American Journal of Managed Care® (AJMC®) and all its brands, including The American Journal of Accountable Care®, Evidence-Based Oncology™, and The Center for Biosimilars®. She has been working on AJMC® since 2014 and has been with AJMC®’s parent company, MJH Life Sciences®, since 2011.

She has an MA in business and economic reporting from New York University. You can connect with Laura on 

The ophthalmology practice of the future will need to manage patients more efficiently and that means incorporating more technology, said Ravi Goel, MD, spokesperson for the American Academy of Ophthalmology and ophthalmologist at Regional Eye Associates in New Jersey.

What changes that occurred as a result of the pandemic do you expect to stay, and are there any you think will get scaled back?

Telemedicine exploded in the early days of the pandemic. In particular, it was essential for patients who had types of care then still needed to be seen, but we couldn't bring them into the office. Telemedicine was wonderful. In my own practice, I implemented parking lot pressures, where I took a patient's pressure in the parking lot, then they went home, and then I did a telemedicine exam with them to manage their glaucoma or sometimes their diabetes and their macular degeneration to do vision screenings outside the office and then follow up through telemedicine.

I think telemedicine is here to stay. I think it will be augmented in the years ahead. I'm excited one of my sessions on The Ophthalmic [Office] of the Future, I look at the fact that virtual reality gadgets, I think, are in their initial stages. I think they will become more and more part of ophthalmic care in the future.

So, I mentioned a few data points to colleagues. Number one is that we estimate the vision loss in the world will go from 1.1 billion individuals to 1.6 billion individuals over the next 30 years. Those are patients who have mild, moderate, or severe visual loss or blindness. In the United States today, 17% of our citizens are over the age of 65—55 million. By 2060 that will be 97 million or 23% of those who live in the United States will be over the age of 65. Ophthalmology tends to skew towards older populations, so we need to figure out ways to better manage our patients—more efficiently manage them. I'm looking to see how Lean management can help our practices.

I'm excited to see what the IRIS registry data and studies that are looking at large population datasets, how that can innovate and help us to treat our patients with higher technologies, more efficient care, leading to better outcomes every day.

The ophthalmology practice of the future will need to manage patients more efficiently and that means incorporating more technology, said Ravi Goel, MD, spokesperson for the AAO and ophthalmologist at Regional Eye Associates in New Jersey.

Dr Ravi Goel Discusses the Future of Technology in Ophthalmic Practice

Matthew is an associate editor for The American Journal of Managed Care® (AJMC®). He joined AJMC® in 2019 and creates content for 

, a 24-hour online program developed MJH Life Sciences® focusing on pressing topics within managed care, as well as the nonwork-related activities of health care stakeholders.

He has a BA in journalism & media studies and economics from Rutgers University. You can connect with Matthew on 

Oral administration of Janus kinase (JAK) inhibitors may provide better efficacy vs topical and sublingual formulations in the treatment of 

 (AA), according to study findings published in 

Although several therapeutic approaches are available for the management of AA, including corticosteroids, minoxidil, and topical immunotherapy, responses to these treatments vary widely, the researchers noted, with adverse events occuring especially frequently in systemic medications.

In exploring more effective and less toxic drugs for AA, targeted therapies, including JAK inhibitors, are considered to be a preferable treatment option. But there remains a lack of comprehensive evidence based on prospective studies regarding the efficacy and safety of these drugs in AA.

“Clinical statistics regarding the efficacy and safety of JAK inhibitors are required to provide a better insight in this new treatment strategy,” wrote the study authors.


They conducted a systematic review and subsequent meta-analysis to evaluate the safety and efficacy of JAK inhibitors for AA. Additional subgroup analyses were conducted to determine the relative efficacy of JAK inhibitors in different administration route (oral vs topical vs sublingual administration) and to identify more factors influencing the good response to JAK inhibitors in patients with AA.

Clinical studies registered in the PubMed, EMBASE, and Cochrane library databases from inception to June 17, 2022 that evaluated the efficacy and safety of the JAK inhibitors tofacitinib, ruxolitinib, baricitinib, ritlecitinib, and brepocitinib were eligible for inclusion in the systematic review.

“The efficacy outcomes included good response (defined as 50% improvement in Severity of Alopecia Tool [SALT] scores), complete response (defined as 90% improvement in SALT scores), the percent change from baseline in SALT score, and recurrence. The safety outcomes included the incidence rates of adverse events,” noted the study authors.

After evaluation of potentially relevant reports, 14 studies (5 randomized controlled trials [RCTs] and 9 non-RCTs), enrolling a total of 1845 patients, were included for quantitative analysis. Non-RCTs included comparative efficacy data on the oral, topical, and sublingual administration of JAK inihibitors, and RCTs included data on only oral and topical formulations.

Specific to RCTs, oral JAK inhibitors exhibited a significantly higher good response rate (RR) compared with controls (RR, 6.86; 95% CI, 2.91-16.16), whereas topical JAK inhibitors did not show any difference compared with controls (RR, 1.00; 95% CI, 0.31–3.18).


The pooled rate of good response in the non-RCTs for oral, topical, and sublingual JAK inhibitors were 63% (95% CI: 44%–80%), 28% (95% CI: 1%–72%), and 11% (95% CI: 1%–29%), respectively, again showing the greater good response observed with oral formulations. No significant difference based on the route of administration was observed for complete response.

Regarding recurrence outcomes, the pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%–69%), mainly due to the withdrawal of JAK inhibitors. No difference was observed in the risk of experiencing adverse events in the RCTs, with reported adverse events with high incidence rate in the non-RCTs indicated to be mostly mild and manageable.

Researchers noted that one of the major limitations of the review was the high heterogeneity of the studies, which could result from the inclusion of 3 routes of administration.


“For this reason, a random effects model was used and subgroup analyses were conducted to reduce heterogeneity,” they added.


They concluded that the high recurrence rate after withdrawal of JAK inhibitors warrants consideration for continuous treatment to maintain efficacy.

Yan D, Fan H, Chen M, et al. The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. 

. 2022;13:950450. doi:10.3389/fphar.2022.950450

Patients with alopecia areata showed improved response rate with oral Janus kinase (JAK) inhibitors vs topical and sublingual JAK inhibitor administration.

Oral Administration of JAK Inhibitors Shows Improved Response in Alopecia Areata

Jaime is a freelance writer for The American Journal of Managed Care® (AJMC®), where she previously worked as an assistant editor.

She has a BA in print journalism from Penn State University. You can connect with Jaime on 

Cemiplimab may yield more favorable outcomes in patients with 

 (NSCLC) with high programmed cell death-ligand (PD-L1) expression and no genomic aberrations, compared with pembrolizumab, say findings from a meta-analysis 

In the absence of a head-to-head trial, the researchers compiled data from randomized controlled trials (RCTs) of the 2 programmed cell death-1 (PD-1)/PD-L1 inhibitors in patients with advanced disease and PD-L1 of at least 50%. Alhough the treatments showed comparable overall survival (OS), cemiplimab was associated with statistically significant improvements in progression-free survival (PFS) and overall response rate (ORR) vs pembrolizumab.

“While each new treatment has provided significant benefits to patients, the clinical evidence base for trials targeting high PD-L1 expression is still evolving and uncertainty remains regarding the most appropriate first-line therapeutic strategies,” wrote the researchers. “Moreover, there are no trials that directly compare the efficacy and safety between these immunotherapies. Such an analysis might help clinicians to optimize immune-oncology monotherapy especially in patients with high PD-L1 expression.”

Data was pulled from 2 pembrolizumab trials—KEYNOTE-024 and KEYNOTE-042—and from the EMPOWER-Lung 1 trial of cemiplimab. The researchers analyzed data from the PD-L1 ≥50% populations, rather than the intent-to-treatment populations, from the EMPOWER-Lung 1 and KEYNOTE-042 trials for efficacy evaluation in order to align with the target population.

At 3 months (HR, 0.81; 95% CI, 0.54-1.19) and 30 months (HR, 0.70; 95% CI, 0.40-1.22), OS with cemiplimab was comparable to that with pembrolizumab, although the researchers noted that at 2 years, more patients receiving cemiplimab were alive, and significantly more were alive without disease progression, compared with patients receiving pembrolizumab. From month 6 (HR, 0.62; 95% CI, 0.15-0.83) through month 30 (HR, 0.32; 95% CI, 0.15-0.68), cemiplimab yielded statistically significant improvements in PFS vs pembrolizumab.

Odds of demonstrating an objective response were also favorable for cemiplimab compared with pembrolizumab (odds ratio, 1.64; 95% CI, 1.04-2.62). Safety between the 2 treatments was comparable, with no evidence of differences in grade 3-5 adverse events (AEs), immune-related AEs, or all-cause discontinuation due to AEs.

In addition to cemiplimab and pembrolizumab, atezolizumab has been approved for this group of patients based on data from the IMpower110 trial; however, this trial was excluded in the current analysis due to an incompatible PD-L1 assay used for patient selection. The MYSTIC trial of durvalumab was also excluded because the treatment is not indicated for monotherapy for advanced NSCLC due to failure to meet the study’s primary end point.

“The current systematic literature review focused only on immune-oncology [IO] monotherapies that were licensed or in the process of being evaluated by the FDA for patients with high PD-L1 expression. Nivolumab monotherapy was excluded since it was not indicated for the target population with high PD-L1 expression, given the unfavorable efficacy results from the CheckMate 026 trial,” the authors concluded. “Future analyses should consider the inclusion of IO combination regimens to assess whether the addition of chemotherapy is beneficial for patients with high PD-L1 expression, as there have been discrepancies in the results from several recently published RCTs and results from indirect comparisons suggest a potential benefit of IO combination regimens for particular subgroups.”

Freemantle N, Xu Y, Wilson F, et al. Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ≥50%. 

. Published online June 16, 2022. doi:10.1177/17588359221105024

In the absence of a head-to-head trial, the researchers compiled data from randomized controlled trials of the 2 PD-1/PD-L1 inhibitors in patients with advanced disease and PD-L1 ≥ 50%.

Cemiplimab Shows Improved PFS, Comparable OS to Pembrolizumab in NSCLC

Edward Arrowsmith, MD, MPH, medical oncologist at Tennessee Oncology’s Chattanooga location, is medical director for clinical pathways for OneOncology. He discussed the challenges in treatment of EGFR Exon 20 insertion+ non-small cell lung cancer (NSCLC), the benefits of next-generation sequencing (NGS), and use of clinical pathways requires a team approach.

®: What are some clinical characteristics seen in individuals with EGFR mutations in non-small cell lung cancer?

 The first thing I would say is that there are no pathognomonic clinical characteristics. Any patient with non-small cell lung cancer has the potential to harbor an EGFR mutation. That's why for anyone with advanced disease or with resected disease eligible for the ADAURA trial with osimertinib1, we recommend testing for EGFR and certainly for advanced disease, broad-spectrum, next-generation sequencing. That said, there are some things that make the presence of an EGFR mutation more likely. The big one is that patients who have never been a cigarette smoker or have been light smokers, usually defined as less than 10 pack-years of smoking, are much more likely to have an EGFR mutation than those who have been heavy, lifelong smokers. Women are probably more likely than men to harbor an EGFR mutation, and then patients of Asian descent also probably more likely to have an EGFR mutation than other ethnicities. There are also some findings clinically, so there's a characteristic sort of ground glass diffuse infiltrates in the lungs that are often seen with EGFR mutations rather than solid central tumors that we might see in squamous cell lung cancer or small cell lung cancer.

®: What are some unique aspects of EGFR Exon 20 insertion+ NSCLC? What makes EGFR Exon 20 insertions more difficult to treat than other EGFR mutations?

 The EGFR insertion mutations in which a base pair is inserted into the DNA strand are really, in my mind, almost a separate disease from the other EGFR mutations. Both Exon 20 and the more typical or classic deletions in Exon 19 or the L858R mutation in Exon 21 cause activation of the EGF kinase and the increased ATPs activity, but they really do so in different ways. The kind of classic mutations do cause a change in the shape of that binding cleft that sort of turn on the gene and protein. The Exon 20 mutations do it in a different way. Some have described it that the deletion 19 abnormality pull open that cleft, whereas the insertions in Exon 20 sort of push open that cleft. When those Exon 20 mutations occur, the phosphate-binding loop or P-loop is pushed into that cleft and that blocks the ability of the classic tyrosine kinase inhibitors like osimertinib or gefitinib or erlotinib to get in and bind to the ATP site and block that abnormality. Those drugs bind in a noncovalent manner to the protein and that bind with that difference in the shape is sort of impossible with the Exon 20 insertion mutations. Those drugs essentially hardly work at all, certainly don't work enough to be a valid therapeutic option for those patients.

®: That makes sense. When it comes to identification of EGFR mutations in non-small cell lung cancer what are some considerations for genetic testing?

 The main finding that [causes] me to recommend genetic or germline testing in patients with non-small cell lung cancer is first, finding a T790M mutation at the initial presentation. That's the classic gefitinib or erlotinib resistance mutation. When we were using those drugs as our initial therapy, we would often start patients and then find that T790M present at the time of progression. It was an on therapy resistance mutation that we would describe to patients as akin to bacterium developing resistance to an antibiotic. When you see that mutation at the initial diagnosis—where they have not been exposed to any agents that would sort of allow that clone to develop—sometimes that's a familial T790M abnormality, and it's worth testing the patient germline and perhaps family members for that. Then, not EGFR-specific, the other place we often find patients with lung cancer with germline mutations is when we are doing comprehensive genomic testing. We do find other genes. We've had an interest in non-tumor-specific clinical trials and have treated many people with 

mutations with lung cancer. BRCA is not in and of itself a risk factor for lung cancer in any way, but it's a common enough mutation—and lung cancer is a common enough disease—that you get that intersection of those 2 by chance. We found patients with lung cancer with Lynch syndrome and other genetic predispositions to cancer that are not risk factored through lung cancer, but we just find them in the comprehensive genomic testing. The other is that when you take a family history, you sometimes will find things that are suspicious. Frequently, the patient, [may not have something suspicious], but they have family members with colon cancer or with breast and ovarian cancer where it's suspicious for those syndromes.

®: Then what are the differences between NGS and PCR testing?

 testing is usually testing for 1 or 2 genes, and what we recommend and the [National Comprehensive Cancer Network] recommends for lung cancer in particular, for most patients with incurable metastatic disease, is comprehensive next-generation sequencing for multiple genes so 300 or more genes. This tests for all the genes that we know of today in non-small cell lung cancer that are targetable, but it also looks for other mutations that could potentially be targets for a clinical trial—or targets for drugs that are in development. Just in the last couple of years, things like the Exon 20 mutations of EGFR or other abnormalities, the KRAS-G12C is another good example of that, where we are finding targets all the time. Having done comprehensive genomic testing allows you to go back and treat those patients appropriately, rather than having to retest and retest in kind of a piecemeal fashion. What we always say is the cost of that comprehensive testing is less than the cost of an admission. It's less about the cost of a PET scan, and we think well worth it to find the best treatment for patients with metastatic cancer.

®: That's a good point. How can clinical pathways be leveraged for rare forms of diseases that may have limited therapeutic options, such as in the EGFR Exon 20 insertion positive non-small cell lung cancer?

 We think one of the core functions of a pathways program is how to make sure that busy clinicians are using the best therapy for rare diseases. Probably the biggest change over the last 10 years or so in cancer care has been splitting common diseases like lung cancer into a huge number of rare diseases, such as Exon 20 insertion mutations of the epidermal growth factor receptor in non-small cell lung cancer. At OneOncology, we have what we like to think of as kind of a dynamic pathways program, where we're both choosing what we think are our optimal therapies for patients and putting that in a PDF, but then also utilizing data analytics, ordering point of care programs to help guide clinicians to remember these rare mutations or rare diseases that there may be therapies that are particularly beneficial for those patients.

The other thing I would add is that we think that analysis of next-generation sequencing reports must be a team effort. Although I was trained to look at bone marrows during hematology fellowship, I always have a hematopathologist also look at the bone marrow slides and interpret things for me. Likewise, I always have people more trained than I am in molecular biology, genetics, and cell biology help me interpret the next-generation sequencing reports or the raw data from those reports so that we can make the best decisions for our patients. We have molecular tumor boards across OneOncology where we have both working tumor boards where we analyze prospectively, the reports that we're getting, and then also molecular educational tumor boards where we look at either new therapies or new understandings of those molecular reports and how to best use that information to treat our patients optimally.

®: That’s leveraging everybody's expertise. How do you approach incorporation of novel therapies for rare diseases such as this one into clinical pathways for care?

 I would say the way we look at pathways is to be comprehensive, to include all abnormalities, including things like the Exon 20 insertion mutations. We look both at things like Exon 20 insertions where they're approved therapies currently and trying to anticipate situations where we expect therapies that might be approved or become standard down the line. In advance of the approval of 2 drugs in the last year or so for Exon 20 mutations, those were patients we were looking for identifying for clinical trials and then rolling into our pathways as standard of care when the data was mature and pointed in that direction. Something else we do is try to have educational programs as new drugs come along to educate our clinicians about these new therapies, their side effects, and the optimal use, and how it may be different in, for instance, Exon 20 mutations versus Exon 19 or 21 mutations, whether those drugs are used first-line and those for Exon 20 are generally a second-line treatment.

®: In closing, can you please provide any closing thoughts on disease management considerations for non-small cell lung cancer, [00:15:00] Exon 20 insertion that you find noteworthy to share with colleagues?

 The thing that I would say that is most important in the management of these rare diseases reiterates what I said earlier, which is, try to have a system to help you find these patients, so you don't overlook them on your NGS report. We're all so busy these days. You don't want to have your system [that lets you] look at a document on your computer the moment before you walk into the patient's room and think that over the course of your career, you won't miss this kind of subtle molecular findings. Build out what works for you in your practice, a way to catch all these patients and flag their charts so that you're treating them optimally, the best therapy for the best patient at the best time. I think the use of pathways to help guide your treatment also helps with that. In this dynamic world where we seem to have 1 or 2 FDA approvals every week, to rely on a pathways team to help guide your treatment is a great way to go.

Wu YL, Tsuboi M, He J, et al for the ADAURA investigators. Osimertinib in resected EGFR-mutated non-small cell lung cancer. 

. 2020;383(18):1711-1723. doi: 10.1056/NEJMoa2027071

Edward Arrowsmith, MD, MPH, medical director for clinical pathways for OneOncology, discussed treatment challenges in EGFR Exon 20 insertion+ non-small cell lung cancer (NSCLC) and best practices in use of clinical pathways.

Edward Arrowsmith, MD, MPH, Discusses EGFR Exon 20 Insertion+ NSCLC, How Knowledge Fits Into Pathways

Making pharmacists part of a comprehensive 

 care model may improve bleeding outcomes, medication access and adherence, and lead to cost savings, according to findings from a 

. The National Hemophilia Foundation (NHF) guidelines for such a model do not currently include a clinical pharmacist.

Implementing a multidisciplinary care team for patients with hemophilia may improve disease management overall, and the NHF-McMaster Guideline on Care Models for Hemophilia Management conditionally recommends that care teams include a range of specialists to improve outcomes: a hematologist, nurse hemophilia specialist, physical therapist, social worker, and specialized coagulation laboratory.

“The goals of such programs are reducing overall bleed rates, patient and family education on appropriate factor dosing, addressing barriers to factor use, coordinating perioperative care, and improving quality of life and overall survival,” the authors wrote. “However, there is little published evidence evaluating the impact of these team members on clinical outcomes, and pharmacists are often not included in the above list of core hemophilia specialists.”

The study evaluated a systems-based quality improvement initiative involving 15 medical center service areas that included pharmacists on core management teams for hemophilia. Pharmacists at a centralized location were added to the care teams and provided telemedicine services to patients. They took comprehensive bleeding histories and developed plans for prophylactic treatment, pre- and postsurgical management, and plans for coagulation factor replacement during episodes of bleeding.

The pharmacists provided additional touch points for patients between follow-up visits, ordered specialized labs for providers, and tailored patients’ medication selections. To minimize product waste, the pharmacists could access vendor inventories to personalize factor vial sizes to best fit a patient’s target dose, and a factor recycling program was implemented to track and dispense unused products with impending expiration dates to patients on regular prophylaxis.

The retrospective analysis assessed patient outcomes and drug costs for 110 patients enrolled in the hemophilia pharmacy service between March 2017 and February 2019 and compared them with data from before and after the program, including March 2016 to February 2020. Bleed rate was calculated as incidence of new bleeds per 100 patient-years, and medication possession ratio (MPR)—the percentage of days that a patient has access to medication within a time frame—was also calculated.

During the program, the annual bleed rate, hospitalizations, and emergency department (ED) visits showed downward trends. The bleed rate was reduced to 37.6 from 40 per 100 patient-years, ED visits dropped from 22.7 to 18.3 per 100 patient-years, and hospitalizations dropped from 6.4 to 3 per 100 patient-years.

“The improvement in communication and additional touch points added by the pharmacy specialists led to earlier identification of bleeds and therapy being administered in the clinic rather than the ED,” the authors wrote. “A reduction in ED visits reduces the overall cost of care for members by affecting copayments, as well as utilization of emergency services within the health care system.”

The number of patients adherent to prophylactic treatment trended upward, and the personalized vial sizes and recycling program significantly reduced waste. In the prestudy period, 9 patients of the 18 on regular prophylaxis (50%) had an MPR of at least 80%, while 11 patients (61%) had and MPR of at least 80% in the poststudy period.

The cost-savings for medication over a 12-month period while the program was ongoing amounted to approximately $900,000. Researchers factored in the conversion of 10 patient therapy regimens to emicizumab, a novel, fixed-dose treatment option, over the study period. Emicizumab is a more expensive prophylactic therapy option for patients with hemophilia A that is subcutaneously rather than intravenously administered.

Overall, the findings suggest that adding clinical pharmacists with hemophilia expertise to care teams may improve medication adherence and outcomes for patients with hemophilia. While the findings regarding clinical outcomes were not statistically significant, the authors attribute this to the small cohort size and baseline involvement of a comprehensive care team prior to the addition of pharmacists. The authors concluded that the model may also benefit other integrated health care systems.

“Pharmacists added tangible value to the care of hemophilia patients and were able to provide stability in patients’ care during transient periods of core team staffing turnover, given their expertise overlapped that of other core team members,” the authors wrote. “Future studies may explore the value of core team members in a randomized fashion to establish the cost effectiveness of their impact on quality of life and clinical bleeding outcomes.”

Lee D, Le AO, Meganck M, Chamberland S, Pai A. Adding a clinical hemophilia pharmacist to the hemophilia comprehensive care model improves health care-related outcomes and drug-related costs in an integrated health care system. 

. Published online August 21, 2022. doi:10.7812/TPP/21.192

A recent study suggests that including a pharmacist in the hemophilia comprehensive care model may improve bleeding outcomes and medication access and adherence, and lead to cost savings.


Adding Pharmacists to Core Hemophilia Care Teams Improves Outcomes, Patient Costs 

Being female, presence of allergic rhinitis, elevated serum total immunoglobulin E (IgE), and elevated blood eosinophil were identified as potential risk factors in individuals who have chronic rhinosinusitis with 

These study findings recently appeared online in 

, and they also show potential of new scoring system—FAIE, or Female, Allergic rhinitis, IgE, and Eosinophil—for screening for these cormobidities.

“Although 20% to 60% of patients with CRSwNP have asthma,” the investigators wrote, “the risk factors associated with comorbid asthma are not clear.”

Patients were matched 2:1, with 150 patients in the modeling group (females, 36.7%; mean age, 48 years) and 78 patients in the validation group (females, 41%; mean age, 48.2 years). Demographic and clinical data on patients in the modelling cohort helped to determine the risk factors and the scoring system.

Following logistic regression analysis, serum total IgE of 69.0 kU/L was shown to have the highest associated risk, of 11 times greater vs those who did not have this IgE level (β 2.483; odds ratio [OR], 12.0; 

 < .001). Presence of allergic rhinitis had the lowest elevated risk, at 1.9 time above that of someone who does not have allergic rhinitis (β 1.070; OR, 2.9; 

Researchers investigated potential risk factors for the higher occurrence of asthma among individuals who have chronic rhinosinusitis with nasal polyps (CRSwNP).