Dr. Andrew Concoff brings tremendous range and unique experience to envisioning the future practice of musculoskeletal medicine. After completing fellowships in rheumatology and sports medicine and a Career Development Award from the National Institutes of Health to study exercise for osteoarthritis, Dr. Concoff has developed novel, hybrid approaches to treating musculoskeletal disorders over the course of over 20 years in private practice. He is also a nationally recognized expert in the diagnostic and procedural musculoskeletal ultrasound in rheumatology and sports medicine. For twelve years, Dr. Concoff supervised a renowned wellness center where he developed evidence-driven physical therapy protocols and holistic care paradigms incorporating mind-body approaches, acupuncture, massage therapy, Pilates, yoga and nutritional interventions.

Dr. Concoff is focused on advancing value in the practice of musculoskeletal medicine as Chief Value Medical Officer for United Rheumatology. He has created innovative programs, supported by economic modeling, to evolve specific aspects of clinical care toward better outcomes and lower costs. His programs span the range of musculoskeletal medicine from shoulder and low back pain to osteoarthritis of the knee, as well as a variety of autoimmune diseases.

“The Sports Rheum I” is an introduction to the clinical interface between rheumatology and sports medicine. Several examples are provided to illustrate the rich opportunities provided by this approach. A general description of the pathophysiology of joint damage in osteoarthritis forms the basis for the complementarity of exercise and pharmacologic intervention in osteoarthritis. Two clinical cases are provided to demonstrate the challenges of diagnosing athletes that present with rheumatic disease. An initial introduction to the application of advanced physical therapy techniques to improve strength without antagonizing affected arthritic joints is also provided. Finally, a description of the application of complementary medicine approaches to musculoskeletal disorders is presented.

Each of these examples will be explored in greater depth in subsequent episodes of The Sports Rheum as a part of The Concoff Method from The Rheum Additional series will explore the challenges of practicing medicine during the COVID-19 pandemic, The COVID Rheum, and efforts to evolve musculoskeletal medicine toward better outcomes and lower costs, The Value Rheum.

In today's issue of Rheumatology Network, we introduce The Concoff Method, a new column by Andrew Concoff, M.D., a rheumatologist who serves as executive vice president and chief value medical officer of United Rheumatology. Over the course of the next year, Dr. Concoff will publish columns that address sports medicine, value in rheumatology and managing a medical practice in the era of COVID-19. In this inaugural issue of the column, he covers the interface between sports medicine and rheumatology. 

Introducing the Concoff Method:  The Interface Between Sports Medicine and Rheumatology

Andrew L. Concoff, MD, FACR, CAQSM

Christopher Parker, DO

Dr. Karp is the 84th president of the American College of Rheumatology. He is chief of the Rheumatic Diseases Division at UT Southwestern Medical Center, Dallas, a role he has held for the past 18 years.

For the past 15 years, Dr. Karp’s research has focused on systemic lupus erythe­matosus, including the of use of genomics and proteomics to help understand disease progression. He joined the ACR during his fellowship and has been involved as a volunteer for the past 17 years, serving in various committee roles, leading the Rheumatology Research Foundation and serving on the ACR Board of Directors’ Executive Committee.

David R. Karp, MD, PhD

1:05 Overview of faricimab and high-dose aflibercept

3:48 clinical trials for faricimab and high-dose aflibercept

9:12 Comparing the matched dose phase results in clinical trials

12:30 Potential impacts of Ang-2 inhibition

14:40 Real-world experience with faricimab

24:00 Choosing between faricimab vs high-dose aflibercept

29:00 Perspectives on retreatment criteria in clinical trials

33:00 Label differences between faricimab and high-dose aflibercept

Retina specialists evaluate the effectiveness of the two new therapies for neovascular AMD and DME by analyzing their respective clinical trial methodologies and outcomes.

Faricimab Versus High-Dose Aflibercept for the Treatment of Neovascular AMD and DME

Jennifer Lim, MD, FARVO, FASRS

panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

Sequence Study of Risankizumab vs Ustekinumab in CD

This is a video synopsis/summary of a panel discussion involving Marla Dubinsky, MD; David Rubin, MD; Miguel Regueiro, MD; Remo Panaccione, MD, FRCPC; and Sara Horst, MD, MPH.

The transcript discusses the findings of the sequence study, focusing on the comparison between two drugs, P41 (referred to as risankizumab) and P19 (referred to as IL (interleukin)-23 therapy). The study aimed to evaluate the efficacy of risankizumab in patients with Crohn's disease who had been exposed to TNF.

The results indicate that risankizumab-exposed patients were more likely to achieve clinical response, clinical remission, and endoscopic improvement compared to those on P40 (risankizumab with IL-12 and IL-23). The transcript emphasizes that the head-to-head comparison provides valuable insights, guiding clinicians in choosing the most effective therapy.

It highlights that risankizumab, along with its biosimilar, is an approved and effective option for Crohn's disease. The discussion touches upon the significance of the sequence study's second primary endpoint, endoscopic remission, and how it could be a pivotal moment in the field.

The conversation also touches on the evolution of clinical trials in Crohn's disease, emphasizing the importance of endoscopic outcomes and the progression from subjective measures to objective proof of efficacy. The participants express optimism about the potential impact of risankizumab, especially when used as a first-line therapy.

Furthermore, the transcript discusses the importance of early intervention in Crohn's disease, suggesting that initiating treatment early is more likely to result in a positive response and prevent further damage. The participants encourage setting higher expectations for patients and discuss the advantages of using risankizumab in biologic treatment-naive patients.

In conclusion, the discussion underscores the positive findings from the sequence study, positioning risankizumab as a promising option for Crohn's disease, particularly in terms of achieving endoscopic remission and improving patient outcomes. The participants stress the need for effective communication with patients about treatment options and the potential long-term benefits of early intervention.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

David Rubin, MD, leads the panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

Miguel Regueiro, MD

Experts discuss strategies for making dry eye care an appealing practice option for optometry students and supporting their success in this specialized field.

Fostering Next-Generation Expertise in Dry Eye Treatment

Fostering Next-Generation Expertise in Dry Eye

Mile Brujic, OD

Multidisciplinary Teams in CKD Management

How can multidisciplinary teams contribute to holistic patient care in managing CKD and associated risks? Why is ongoing education and collaboration across disciplines crucial in enhancing CKD care?

What protocols for screening and testing have you established for your health system to improve the outcomes of patients with type 2 diabetes at risk for or currently diagnosed with CKD? What are some challenges with implementing your protocol?

Chronic kidney disease (CKD) in Type 2 Diabetes patients necessitates early detection to prevent progression and associated complications. Identifying at-risk patients involves considering factors such as hypertension, family history of kidney disease, and elevated blood glucose levels. Screening tests include estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Early detection is crucial as it allows timely intervention, potentially slowing disease progression and reducing cardiovascular risks. CKD is a significant risk factor for heart failure, making early detection vital for comprehensive cardiovascular risk management.

Panelists discuss how multidisciplinary teams can enhance holistic patient care in managing chronic kidney disease (CKD) and its associated risks, emphasizing the importance of ongoing education and collaboration across disciplines, along with established protocols for screening and testing in health systems and the challenges faced in their implementation for patients with type 2 diabetes at risk for or currently diagnosed with CKD.

Rajiv Agarwal, MD

COVID-19 has obviously presented significant challenges in our clinical work, particularly in the evaluation, diagnosis, and treatment of patients with ADHD [attention-deficit/hyperactivity disorder] of all ages. What we’ve all done, of course, is acclimate to this, largely through the use of telemedicine, telepsychiatry for a lot of our patients. Although more recently, I’ve gone back to more of a hybrid model where I am seeing some patients live and some via telepsychiatry. 

There are significant challenges. Some of those challenges include the fact that it’s a little more difficult to do an evaluation and to collect all the nonverbal information that you might get from being in the room with a person. Part of the problem is you may be seeing only a portion of the patient’s body. You may not be seeing the lower half of the body if you’re on a virtual call. You might not see some of the fidgeting or hyperactivity, for instance.

Also, what I find is patients either do really well with virtual telepsychiatry or don’t. They have trouble focusing. They get distracted. It’s really important to try to individualize care for our patients. Some people try to do in-person meetings. Ideally, this may be helpful for the initial evaluation so we can collect as much information as possible. When you’re dealing with children, you’d like to have collateral information, so you’d like to have parents and caregivers involved. That can be a little harder too, although it can be done virtually.

As far as prescribing medications, that can present a challenge. Although now, states are going to e-prescribing. In Florida, we now have to e-prescribe all controlled substances. That makes it easier, not having to handwrite a prescription and somehow get it to the patient in a COVID-19 environment.

The other thing I find is that sometimes children do a little better in this virtual environment, but many with ADHD struggle more. There’s a lot more stress and difficulty in school. Obviously, there’s more isolation, so fewer social relationships, fewer extracurricular activities, and maybe less access to exercise, which has been shown to be very beneficial for ADHD. These are some of the challenges that we’re trying to negotiate in the era of COVID-19.

Tele-prescribing of stimulants presents some unique challenges in the era of COVID-19. Part of the challenge is making sure you can e-prescribe appropriately. Most of us have figured out how to do that. Also, you want to make sure the pharmacy is available and shows up on your e-prescribing software. It is required, when we prescribe stimulants, that we monitor certain things. This can be more challenging in this environment, particularly when assessing vital signs, height, and weight. Blood pressure, heart rate, height, and weight can be a challenge in the virtual environment. This is when I may sometimes have the patient come to the office, just for the vital signs and height and weight checks. Or the patient can get 1 of the home monitoring devices, which you can get at many pharmacies. These devices can monitor blood pressure and heart rate. Your patients can check those periodically and report the results to you. Or you can certainly have them email that to you or communicate electronically.

As far as monitoring for abuse and possibility of diversion, this is something we also need to keep our eyes on. We can do this in various ways, including by checking prescribing databases, which can certainly be done online.

As far as monitoring for other issues and problems, such as the emergence of psychotic or manic symptoms or the possibility of vasoconstriction or cardiovascular issues, this is where taking a very careful history and evaluation and trying to look at the patient and evaluate them as best you can on camera really seems to help.

It’s important to understand that when evaluating and treating ADHD, comorbidity is the rule. Three-quarters of patients with ADHD will have a least 1 other comorbid condition. This is important because sometimes our core treatments for ADHD can help alleviate these other conditions. For instance, secondary anxiety or secondary depression. Sometimes, however, we do have to institute specific treatment in addition to the ADHD treatment to address a comorbid condition.

Rakesh Jain, MD, MPH: When parents and their children first come to see me for an evaluation for ADHD, there’s often a lot of confusion. We have a lot of myths in our heads. “Is this bad parenting?” “Was this just because one of us got divorced?” Is it because I had too many Diet Cokes when I was pregnant?” 

My first job is to offer parents and children a combination of sympathy and encouragement. I offer sympathy for the suffering they have gone through and encouragement that, if we do the right thing, we can make a pretty significant difference in all the challenges your child is having and you’re having as parents and caregivers. I have found that injection of enthusiasm, support, and knowledge to be as useful as anything I do.

The second step is really a pretty quick but accurate increase in knowledge base about the disease. Most people are quite surprised to know that it is a neurobiologically active condition. It is an inherited condition. It is a brain-based condition. Even though behavior is what they might see, the child is not being a “bad” child. 

Finally, we need to give an explanation of why interventions work or why a combination of nonpharmacological and pharmacological interventions is best explained in the context of neurobiology. 

When I offer that whole package of information, from sympathy to increasing their enthusiasm and encouragement to disease-state knowledge and then finally medication and nonmedication knowledge, you can see the parents and the child breathe a sigh of relief. “I’ve got a direction. There’s something I can do. I feel empowered.” That is precious. As a clinician, once I see that, I know I have established a solid therapeutic relationship that will lead to good outcomes.

Optimizing care and managing challenges for patients with ADHD during the COVID-19 pandemic and advice for clinicians educating patients and families on disease management. 

Optimizing Care for ADHD During COVID-19 

Rakesh Jain, MD, MPH, Texas Tech University School of Medicine

Geoffrey Grammer, MD closes this series highlighting the administration options of esketamine, its safety profile, and the importance of monitoring patients using this treatment.

Esketamine Safety Mechanisms and Bioavailability

Robert Zalewski-Zaragoza, MD

Virginia Clark, MD, is a professor of medicine and program director of the gastroenterology fellowship in the division of gastroenterology, hepatology, and nutrition at the University of Florida.

Virginia Clark, MD: Understanding Fazirsiran’s Potential in AATD Liver Disease

New data from the open-label extension of the phase 2b SEQUOIA study of fazirsiran support the investigational small interfering RNA therapy’s long-term safety and efficacy in patients with 

The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD)

 in San Diego, California, by Virginia Clark, MD, a professor of medicine and program director of the gastroenterology fellowship in the division of gastroenterology, hepatology, and nutrition at the University of Florida.

, Clark described AATD as being frequently overlooked and underdiagnosed, explaining the importance of establishing the presence of fibrosis and cirrhosis to determine the next steps in disease management.

In the absence of an approved therapeutic option for the treatment of AATD-associated liver disease, transplantation is the only choice for patients who develop more severe complications. For patients with stage 2 or 3 fibrosis who fall in the “gray zone” and are at high risk of progression, Clark pointed to the promise of investigational agents in clinical trials.

“These new therapeutic agents may have the potential to reduce the toxic burden of the alpha-1 within the liver, and that may change the trajectory of what their disease does over time,” she explained.

A hepatocyte-targeted investigational RNA interference therapeutic, fazirsiran is designed to degrade alpha-1 antitrypsin and mutant misfolded Z alpha-1 antitrypsin (Z-AAT) messenger RNA in hepatocytes, subsequently reducing protein synthesis and inhibiting further accumulation of Z-AAT polymers to allow normal cellular mechanisms to dispose of mutant proteins.

The SEQUOIA trial enrolled 40 adults with Pi*ZZ AATD who were randomly assigned to receive fazirsiran at doses of 25 mg, 100 mg, or 200 mg, or placebo for ≤ 148 weeks. One-year findings showed treatment with fazisiran resulted in sustained, dose-dependent reductions in Z-AAT concentration and improved histological findings, including periodic acid-Schiff staining with diastase digestion (PAS+D) globule burden, a hallmark of AATD-associated liver disease.

Patients with fibrosis at screening and a post-dose liver biopsy at week 48, 72, and 96 entered the open-label extension and received fazirsiran 200 mg every 12 weeks for a total treatment period of ≤ 197 weeks. In total, 23 patients received ≥1 dose of fazirsiran during the open-label extension, 14 of whom received fazirsiran (FAZ–FAZ cohort) and 9 of whom received placebo (PBO–FAZ cohort) during the double-blind study phase.

“No real pulmonary complications were seen over placebo and the pulmonary function tests were stable, so that is very encouraging in the short-term,” Clark explained.

In addition to stable mean percent predicted pulmonary function in both cohorts and improved mean laboratory measures in the PBO–FAZ cohort, results showed serum Z-AAT levels reduced by a mean of 36.3% (Standard deviation [SD], 34.1) for the FAZ–FAZ cohort and 85.5% (SD, 13.1) for the PBO–FAZ cohort. Among the 20 patients who reported a treatment-emergent adverse event in the open-label extension, most were mild or moderate and 1 led to study withdrawal.

“The findings were very consistent with what we'd already seen in the first 2 studies, which was decreased liver tests and stain reduction in how much alpha-1 could be measured within the serum,” Clark said. “Overall, the results were very promising, quite consistent, and really support further development of this drug for treatment of alpha-1.”

Editors’ note: Clark has relevant disclosures with Vertex, Takeda, and Novo Nordisk.

Clark V, Strange C, Strnad P, et al. Long-term safety and efficacy of fazirsiran in patients with alpha-1 antitrypsin deficiency-associated liver disease enrolled in the phase 2 placebo-controlled SEQUOIA trial. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Brooks, A. SEQUOIA: Fazirsiran Reduces Serum, Liver Z-AAT Concentrations, Improves Hepatic Globule Burden. HCPLive. July 10, 2024. Accessed December 17, 2024. 

https://www.hcplive.com/view/sequoia-fazirsiran-reduces-serum-liver-z-aat-concentrations-improves-hepatic-globule-burden

Clark reviews open-label extension data from the phase 2b SEQUOIA study of fazirsiran for AATD liver disease.

Authors