Total knee arthroplasty (TKA) procedures are one of the most common surgeries in the United States and the demand for TKA procedures continues to increase every year. Annually, 

approximately 790,000 knee replacement surgeries

 are performed, and that number is projected to be 

. While recovery protocols have evolved over the years, surgeons are taking a closer look at how they can improve different aspects of the recovery process with new technology, research, and medications, including non-opioids.

Dr. Vinod Dasa, Professor of Clinical Orthopaedics and Director of Research at LSU Health in New Orleans, is sharing a new analysis about rapid recovery protocols (RRPs) that can enhance and improve patient outcomes following TKA procedures. His goal is to educate clinicians about innovative approaches and medical advancements related to multimodal pain management protocols including using NSAIDs, acetaminophen, local anesthetics, cryotherapy, physical therapy and more.

Like many surgeons, Dr. Dasa and his team were using standard recovery protocols (SRP) to treat patients after total knee replacement surgeries. The SRP included using a femoral nerve block, spinal anesthesia, multimodal analgesia and limited patient education prior to surgery. After considering new advancements in the field, Dr. Dasa and his team set out to revamp the TKA recovery process and develop a protocol that would allow their patients to get back to their day-to-day activities sooner.

A vital component to the new RRP was implementing a coordinated effort from every person involved in the surgical and recovery journey including surgeons, physical therapists, operating room staff, and nurses. Further, the new process included engaging and educating patients about the procedure, technology, and pain management options used throughout the perioperative period. Communication from all of these people throughout the surgical journey was a crucial component of the process.

The team also needed to determine how to measure success for patients following TKA. Two main factors that were evaluated as part of the RRP were range of motion (ROM) of the knee and length of stay (LOS) in the hospital. ROM is measured both before and after surgery using a goniometer, or a compass used by surgeons to calculate precise angles. LOS is determined by the number of calendar days a patient remains in the hospital after the completion of their surgery.

Advances in Pain Management Techniques Prior to Surgery

While Dr. Dasa and his team implemented basic changes (e.g., team approach, improved communication) they also incorporated more technical ones. Recently, attention has turned to the use of presurgical techniques to reduce pain and opioid use associated with knee arthroplasty. Novel platforms, such as cryoneurolysis also known as 

°, have been applied to prospective TKA patients to reduce pain and opioid use. One-to-two weeks before surgery, Dr. Dasa’s team uses this cryotherapy treatment to treat peripheral nerves and immediately reduce pain by using the body’s natural response to cold. This step freezes the sensory nerves prior to surgery and helps patients feel more confident about pain management throughout the surgical process.

Techniques to Manage Pain Intraoperatively

Local infiltration anesthesia (LIA) has become a standard practice for a number of joint procedures over the years. Dr. Dasa and his team use 

® (bupivacaine liposome injectable suspension), a long-acting local anesthetic injected near the surgical site, which slowly releases a numbing medication to provide pain relief for the first couple days after surgery. LIA like EXPAREL have improved enhanced recovery pathways for Dr. Dasa’s patients. After surgery, he encourages clinicians to quickly enroll patients in postoperative physical therapy. Additionally, he reassesses the multimodal pain management strategy by limiting or eliminating the use of opioids to manage pain after surgery.

When using a multimodal approach, including the use of cryoneurolysis, NSAIDs, acetaminophen, local anesthetics, and physical therapy to manage postsurgical pain, Dr. Dasa and his team found that patients’ overall LOS in the hospital decreased. Historically, patients undergoing knee replacements with a standard recovery protocol would stay in the hospital for a few days; however, with the RRP group the LOS decreased to less than one day for most patients. In addition, Dr. Dasa noted the RRP was associated with a higher flexion, or range of motion, in the 12 weeks after the procedure. Dr. Dasa has also seen many patients in the last year reduce their opioid consumption, only taking mild pain relievers following TKA using this novel, multimodal, team-based approach.

The findings from this latest research are encouraging as it points to a multimodal pain management approach enhancing recovery for patients after TKA procedures. Dr. Dasa is dedicated to continuing sharing information about the latest medical advancements, including the use of non-opioid options, with his peers to continue to provide optimal results for his patients.

The iovera° system is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The iovera° system is not indicated for treatment of central nervous system tissue. The iovera° system’s “1x90” Smart Tip configuration (indicating one needle which is 90 mm long) can also facilitate target nerve location by conducting electrical nerve stimulation from a separate nerve stimulator.

The iovera° system is contraindicated for use in patients with the following:

Cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, Raynaud’s disease, and open and/or infected wounds at or near the treatment site

As with any surgical treatment that uses needle-based therapy and local anesthesia, there is a potential for site-specific reactions, including, but not limited to:

Ecchymosis, edema, erythema, local pain and/or tenderness, and localized dysesthesia

Proper use of the device as described in the User Guide can help reduce or prevent the following complications:

At the treatment site(s): injury to the skin related to application of cold or heat, hyper- or hypopigmentation, and skin dimpling

Outside the treatment site(s): loss of motor function

EXPAREL is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Safety and efficacy have not been established in other nerve blocks.

EXPAREL is contraindicated in obstetrical paracervical block anesthesia

Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation

If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine

EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients

Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease

Warnings and Precautions Specific to EXPAREL

Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL

EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks 

other than interscalene brachial plexus nerve block

, or intravascular or intra-articular use

The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials

Warnings and Precautions for Bupivacaine-Containing Products

 There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression

 Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death

 Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients

 There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use

 Cases of methemoglobinemia have been reported with local anesthetic use

Articles

How Novel Technologies and Opioid Alternatives Can Improve Patient Outcomes

Revamping Recovery Protocols with Non-Opioid for TKA Procedures

Uncovering the unseen and unspoken signs of eosinophilic esophagitis

“I don’t know what’s going on, but it’s been really hard for me to swallow and it feels like I’m ‘choking’ on my food when I eat.” A 35-year-old male visits your office telling you what brings him in today. When you ask how long this has been happening, he says 15 years, since college. As your conversation continues, you learn he also has heartburn in addition to his dysphagia.

When you ask what prompted him to see you after all this time, he explained the impact on his day-to-day life: the anxiety of having a choking episode at a work dinner or a date. “I’m 35 years old,” he says. “I should’ve been able to figure out how to eat without any issues by now.”

For many patients, the road to an Eosinophilic Esophagitis (EoE) diagnosis can be a long, difficult journey.

 As a disease that is growing in prevalence

, EoE is a chronic, immune-mediated inflammatory disease localized in the esophagus.

 While the exact cause of EoE is unknown, researchers believe several variables play a role, including genetics, environmental factors, immune system dysfunction

EoE impacts an estimated one in 2,000 people

 of all ages and races in the U.S. While both men and women may be affected, men are approximately twice as likely to develop EoE.

The chronic, persistent inflammation of the esophagus can lead to a range

 of symptoms that manifest differently from patient to patient. Younger children including toddlers may exhibit feeding avoidance or intolerance, regurgitation, and vomiting. Older children may have similar symptoms and may also have chest or abdominal pain, and adolescents more often also have dysphagia as well as food impactions in some cases. While adults can experience all of these symptoms, dysphagia is the most frequently reported symptom. Adults with unrecognized, long-standing inflammation and potential esophageal scarring can also experience episodes of food impaction.

Patients with EoE may also present with psychiatric comorbidities.

 One retrospective study found that one-third of adults and one in seven children with EoE have received a diagnosis of a psychiatric condition, like anxiety or depression.*

People with EoE can develop adaptive behaviors to cope with everyday life, especially to manage their symptoms when eating.

Substituting solids with blended or pureed foods

Earlier detection is important as it can help reduce a patient’s potential risk of disease complications.

However, identifying EoE can be complex and delayed diagnosis is common among patients, up to eight years on average for adults according to one systematic review.

Several factors can contribute to these delays. EoE can be under-recognized among specialists.

 Symptoms may also be under-reported by patients — around 50 percent of dysphagia cases may not be discussed with a physician,

** yet it’s the most common symptom of EoE.

Additionally, EoE symptoms can mimic other more common diseases such as gastroesophageal reflux disease (GERD)

 and patients can also present with one or more atopic disorders, such as asthma, rhinitis, atopic dermatitis and food allergies, making it challenging to assess and diagnose.

An EoE diagnosis first begins with a look at the patient experience. Patients should present with esophageal symptoms; however, physicians must be astute to adaptive behaviors and the potential for these behaviors to mask physical symptoms.

Endoscopic and histopathologic results are other critical factors to consider.

 An endoscopy can help assess severity of EoE based on specific features, including edema, rings, exudates, furrows, and strictures.

 Of those with EoE, up to approximately 25 percent have normal endoscopic findings.

*** Current guidelines stipulate that esophageal biopsy results demonstrate an eosinophil count of ≥15/hpf (high-power field) for a diagnosis of EoE with biopsy samples taken from multiple levels of the esophagus.

The diagnosis of EoE is made by this confirmation of esophageal eosinophilia on biopsies in patients who have signs and symptoms of esophageal dysfunction that are not explained by another underlying condition.

In combination with the presence of esophageal eosinophilia, the assessment of symptoms and endoscopic findings are important in the evaluation for and diagnosis of EoE.

EoE is not a condition that should be overlooked. The signs of EoE must be seen, spoken about and managed.

Earlier this year, guidelines for the management of pediatric and adult patients with EoE were published by the American Gastroenterological Association and the Joint Task Force for Allergy-Immunology Practice Parameters (The American Academy of Allergy, Asthma, and Immunology and American College of Allergy, Asthma and Immunology). These guidelines strongly recommend that physicians use topical glucocorticosteroids over no treatment in patients with EoE, and conditionally recommend use of proton pump inhibition therapy, an elemental diet, dietary elimination treatments, and esophageal dilation.

Endoscopic esophageal dilation is a mechanical treatment of stricture to improve symptoms and is not regarded as impacting underlying inflammation.

 To date, there are no FDA-approved therapies indicated for the treatment of EoE.

If left untreated, EoE can cause injury and inflammation to the esophagus.

 Chronic inflammation in EoE can change the way patients eat, which could negatively impact their social lives. It can also be a burden for parents of children with EoE.

As healthcare professionals, it is important to ask open-ended questions that can help to identify adaptive behaviors that, when thought of as normal by patients, may prevent the recognition of dysphagia and other symptoms that may signal EoE. Importantly, it is key to assess and continue monitoring all three domains – symptoms, endoscopy and histopathology – when diagnosing and caring for people with EoE.

 With this approach, the pathway to a diagnosis of EoE can potentially be shortened and we can sooner help patients address and manage the manifestations of chronic inflammation in the esophagus and symptomatic burden of the disease.

For more information about the unseen and unspoken signs of EoE, please visit 

*In a study using the University of North Carolina EoE Clinicopathologic Database from 2002 to 2018. Of 883 patients diagnosed with EoE (per consensus guidelines), 241 (28%) had a psychiatric comorbidity. Study limitations include this is one, single center, retrospective study where a comparison to the national representative figures was done through non-statistical analysis.

**In an online April 2018 Takeda sponsored self-administered health survey of 31,129 people, 4,998 people reported dysphagia; however, only half sought healthcare for it. Of these people, 399 confirmed an EoE diagnosis.

***In a retrospective study of 117 patients with EoE, the esophageal mucosa was regarded as normal in 24.8% of the patients.

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5. O'Shea KM, Aceves SS, Dellon ES, et al. 

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 2019;pii:S1542-3565(19)31182-6.doi:10.1016/j.cgh.2019.10.029.[Epub ahead of print].

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24. Menard-Katcher P, Marks KL, Liacouras CA, et al. 

25. Klinnert M, Silveira L, Harris R, et al. 

27. Hiremath G, Kodroff E, Strobel M, et. al. 

Eosinophilic Esophagitis: The Challenging Journey to Diagnosis

Murdo Gordon, Executive Vice President, Global Commercial Operations for Amgen is responsible for ensuring Amgen’s innovative medicines reach patients around the world.

Although the world is focused on the COVID-19 pandemic, heart disease remains one of the most important public health issues of our time and we can’t lose sight of the significant impact it continues to have on our society. To put this in context: a heart attack strikes every 40 seconds in the U.S., which is almost 800,000 heart attacks every year.

 Of those, 25% are recurrent heart attacks in people who have already suffered at least one earlier in life.

 For this reason, Amgen is committed to continued research and development in this field because we need more innovation, not less, to help these patients.

This past summer marked the fifth anniversary of regulatory approval for Repatha® (evolocumab)— Amgen’s innovative cholesterol-lowering medicine. Repatha® is also proven to reduce the risk of another heart attack for patients with established cardiovascular disease.

It took our scientists more than a decade to research, develop and make Repatha® available to patients. But in today’s healthcare environment, medical innovation is not enough. Affordability is a necessity—especially for people who need a medicine like Repatha® to reduce the risk of another life-changing heart attack.

That’s why Amgen reduced the list price of Repatha® by 60% and worked with insurance companies and pharmacy benefit managers to reduce access barriers over the past year. We’re pleased to report that we’ve made significant progress for patients. It’s about time!

Today, more than 80%* of prescriptions for Repatha® patients have an affordable co-pay of less than $50 per month.

 And eligible commercial patients could pay as little as $5 per month with the Repatha® Copay Card

. Further, many access barriers have been addressed, and now, eight out of 10 patients

We’re committed to keeping Repatha® affordable and reducing barriers to access for everyone who needs Repatha®, and we are not going to stop. You can count on us because every heart counts.

 Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.

 Hypersensitivity reactions (e.g. angioedema, rash, urticaria) have been reported in patients treated with Repatha®, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.

Adverse Reactions in Primary Hyperlipidemia (including HeFH):

 The most common adverse reactions (>5% of patients treated with Repatha® and occurring more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.

From a pool of the 52‐week trial and seven 12‐week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®‐treated and placebo‐treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising.

Allergic reactions occurred in 5.1% and 4.7% of Repatha®‐treated and placebo‐treated patients, respectively. The most common allergic reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).

Adverse Reactions in the Cardiovascular Outcomes Trial:

 The most common adverse reactions (>5% of patients treated with Repatha® and occurring more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).

Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new‐onset diabetes mellitus during the trial was 8.1% in patients assigned to Repatha® compared with 7.7% in those assigned to placebo.

 Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.

In adults with established cardiovascular disease, Repatha® is indicated to reduce the risk of myocardial infarction, stroke, and coronary revascularization.

Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia): 

Repatha® is indicated as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia to reduce low-density lipoprotein cholesterol (LDL-C).

For more information on how to access Repatha®, please visit 

*Based on IQVIA claims data from 01/2020 to 08/2020 using Commercial, Medicare, and Medicaid claims.

†Eligibility requirements for the Repatha® Copay Card: Open to patients with commercial prescription insurance and who are not enrolled in any government-funded program that pays for prescription drugs. This program is not open to uninsured patients or patients enrolled in any federal-, state-, or government-funded healthcare program such as Medicare, Medicare Advantage, Medicare Part D, the Retiree Drug Subsidy Program, Medicaid, Medigap, Veterans Affairs (VA), the Department of Defense (DoD) or TRICARE®, or where prohibited by law. Cash Discount Cards and other noninsurance plans are not valid as primary insurance coverage under this offer. Other restrictions, including annual copay maximum limits may apply. This offer is subject to change or discontinuation without notice. Please visit Repatha.com for full terms and conditions.

‡Based on MMIT data as of 09/2020 for Commercial, Medicare, and Medicaid lives.

 Benjamin, EJ, et al. Circulation. 2019; 139: e56-e528.

Amgen's Commitment to Helping Make Repatha® Affordable for All

Rheumatoid arthritis (RA) is a complex, systemic autoimmune disease that is well known but not well understood. One related consequence – 

many people living with RA do not achieve remission.

Many continue to struggle daily through painful joints and fatigue, unable to do many of the things that they used to.

The good news? The heightened community focus on research and development can help change this storyline.

Remission or low disease activity are the primary goals of RA treatment as defined by the American College of Rheumatology (ACR) guidelines.

But not all patients can get there despite the progress in the management of RA over the last couple of decades. This challenge is what drives all of us who work in this field each day.

Early in my career as a rheumatologist, there were fewer treatment options available for moderate to severe RA. For many patients who had an RA diagnosis, chronic pain, irreversible joint deformities and loss of function are what slowly unfolded before their eyes over time. Fortunately, tumor necrosis factor (TNF) inhibitors soon came to the clinic, which helped to address these challenges. As a physician, I went from managing recurrent flares and having the difficult conversation about joint damage, to counseling patients that with these new biologic therapies, they may have a better chance of managing their RA symptoms. Having seen how achieving remission affected the lives of some of my patients, I knew the work was not done until this became a reality for more RA patients.

When I decided to join AbbVie, I was in search of an opportunity to do clinical research that would advance the care of rheumatology patients. Today, I lead a team of physicians and scientists who design and execute clinical trials that evaluate investigational new compounds to treat immune-mediated inflammatory diseases. Our mission is focused on advancing the standard of care for the treatment of the diseases for which we work. The challenge in RA was to develop a new therapy that could elevate treatment expectations and help more patients reach their treatment goals. We knew that different patients respond differently to any given therapy so we needed to better understand what new pathways we could target.

My colleagues in drug discovery focused on the hypothesis that inhibition of certain Janus Kinases (JAK) could deliver a positive benefit-risk profile in RA patients. Years of diligent work led to the discovery of upadacitinib, now known as RINVOQ™, an oral JAK inhibitor that was approved by the U.S. Food and Drug Administration (FDA) in August 2019 for the treatment of adults with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.

In developing RINVOQ to treat moderate to severe RA, we knew it was necessary to design a comprehensive program so we could have a good understanding of the optimal use of this compound for various types of patients. Our team evaluated RINVOQ in one of the largest registrational Phase 3 programs in RA with approximately 4,400 patients evaluated across all treatment arms in five studies. The SELECT studies included assessments of efficacy, safety and tolerability across a variety of patients with moderate to severe disease from those who were naïve* or intolerant to methotrexate, to patients who had failed or were intolerant to biologic disease-modifying anti-rheumatic drugs. Results from the five pivotal trials showed:

RINVOQ met all primary (ACR20 or ACR50 at Week 12 or 14) and ranked secondary endpoints in all five studies

Remission rates with RINVOQ (as assessed by DAS28-CRP<2.6†) were observed at week 12 or 14 with durable rates through week 26

RINVOQ significantly inhibited radiographic progression with or without methotrexate at week 24 or 26*

We have made progress in our understanding of RA and in our ability to develop new effective medicines for patients living with this disease. With the multiple therapies available today, rheumatologists can better address each patient’s unique needs and more patients can reach their individual treatment goals, something I hoped for when I was still in clinic. I am fortunate and proud to have been a part of making RINVOQ a viable treatment option for many patients.

* RINVOQ is not indicated for MTX-naive patients.

†Does not mean drug-free remission or complete absence of disease.

RINVOQ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine, is not recommended.

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent infection prior to RINVOQ use.

Invasive fungal infections, including cryptococcosis and pneumocystosis.

Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

Carefully consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Lymphoma and other malignancies have been observed in patients treated with RINVOQ. 

Consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or in patients who develop a malignancy. NMSCs have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions. Many of these adverse events were serious and some resulted in death. Consider the risks and benefits prior to treating patients who may be at increased risk.Patients with symptoms of thrombosis should be promptly evaluated.

Gastrointestinal perforations have been reported in clinical studies with RINVOQ, although the role of JAK inhibition in these events is not known. In these studies, many patients with rheumatoid arthritis were receiving background therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). RINVOQ should be used with caution in patients who may be at increased risk for gastrointestinal perforation. Promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation.

Treatment with RINVOQ was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3). Treatment with RINVOQ is not recommended in patients with an ANC <1000 cells/mm3. Evaluate neutrophil counts at baseline and thereafter according to routine patient management.

Absolute lymphocyte counts (ALC) <500 cells/mm3 were reported in RINVOQ clinical studies. Treatment with RINVOQ is not recommended in patients with an ALC <500 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.

Decreases in hemoglobin levels to <8 g/dL were reported in RINVOQ clinical studies. Treatment should not be initiated or should be interrupted in patients with hemoglobin levels <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.

Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Manage patients according to clinical guidelines for the management of hyperlipidemia. Evaluate 12 weeks after initiation of treatment and thereafter according to the clinical guidelines for hyperlipidemia.

Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded.

Based on animal studies, RINVOQ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose. Verify pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.

Use of live, attenuated vaccines during, or immediately prior to, RINVOQ therapy is not recommended. Prior to initiating RINVOQ, patients should be brought up to date on all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.

There are no data on the presence of RINVOQ in human milk, the effects on the breastfed infant, or the effects on milk production. Available data in animals have shown the excretion of RINVOQ in milk. Advise patients that breastfeeding is not recommended during treatment with RINVOQ and for 6 days after the last dose.

RINVOQ is not recommended in patients with severe hepatic impairment.

The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, nausea, cough, and pyrexia.

 Medicines Matter Rheumatology. JAK inhibitors: The next generation of drugs for treating rheumatoid arthritis? 

https://rheumatology.medicinematters.com/rheumatoid-arthritis-/jak-inhibitors/jak-inhibitors-the-next-generation-of-drugs-for-treating-rheumat/12336972

 American College of Rheumatology. Rheumatoid Arthritis. Available at: 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis

American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 

https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf

RINVOQ™ [Package Insert]. North Chicago, Ill.: AbbVie Inc.

Elevating RA Treatment Expectations

Dr. Mitesh Borad, Oncologist, Associate Professor of Medicine at Mayo Clinic College of Medicine and Science

Cholangiocarcinoma (CCA) is a rare and often overlooked cancer that forms in the bile duct. Rare in that it affects fewer than 10,000 people in the U.S.,

 but overlooked likely because of its non-specific symptoms — including abdominal pain, night sweats, fatigue, jaundice, general discomfort and weakness – which can make it difficult for physicians to identify.

 Too often, CCA becomes a diagnosis of exclusion, only determined after physicians undergo rigorous processes to rule out other potential explanations to reach a diagnosis. As such, CCA is often diagnosed at an advanced stage when curative modalities such as surgery are not feasible and the prognosis is poor.

Given the non-specific nature of symptoms associated with the diagnosis of CCA, other than jaundice, early detection is uncommon. In my own practice, I have found that a growing number of patients are being incidentally diagnosed by the presence of lesions, which are identified through imaging in the absence of other typical CCA symptoms.

Historically, the only potentially curative treatment for CCA has been surgery, but even after surgery, relapse rates are high, and patients have a median survival of only about 12 months.

 More recently, technological interventions are making it possible to more efficiently evaluate CCA by allowing researchers to look closely inside each person’s tumors to see exactly which mutations are present. 

This type of testing, called molecular profiling, pinpoints driver mutations, or genomic abnormalities.

 Molecular profiling can help detect these abnormalities earlier on in disease progression.

For example, FGFR2 fusion or rearrangement is observed in 10 — 15% of patients whose CCA originates in the bile ducts within the liver, known as intrahepatic CCA.

While a variety of molecular profiling methods are now available, next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are among the most common. NGS allows us to analyze a tissue sample for multiple alterations at the same time, while FISH tests are conducted to identify one specific, predetermined alteration at a time.

Molecular profiling isn’t consistently conducted, and it often isn’t even considered until after first-line chemotherapy has failed. Knowing that, I encourage patients within my practice to undergo molecular profiling early on in a patient’s CCA diagnosis, and I urge my hepatology and gastroenterology colleagues to do the same.

It is critical that physicians understand the importance of early molecular profiling when it comes to treating patients with CCA. More broadly, molecular profiling has helped scientists and physicians better understand how cancer can start, grow and spread in the body.

For more information on FGFR2 fusions and next generation sequencing in cholangiocarcinoma, visit 

[i] Key Statistics for Bile Duct Cancer. American Cancer Society. 

https://www.cancer.org/cancer/bile-duct-cancer/about/key-statistics.html

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