Advertorial content funded and developed by GSK.


Asthma is a disease of the lungs characterized by chronic airway inflammation and fluctuating airflow limitation.

 It is associated with wheezing, breathlessness, chest tightness, and coughing at night or the early morning.

 Approximately 25 million people in the United States have asthma, with over 8% of adults and nearly 6% of children affected by this common condition.

When a person’s asthma requires use of high-dose corticosteroid inhalers or oral steroids to prevent it from being uncontrolled, or it remains uncontrolled despite these medicines, it is referred to as severe asthma.

 Severe asthma involves recurrent exacerbations, reduced lung function, and worsening asthma control.

 Up to 10% of the asthma population has severe or refractory disease, which accounts for disproportionately high health care costs due to suboptimal treatment responses and worsening symptoms.

 Additionally, increased asthma severity and poorer disease control are independent predictors of death.

Although the complete pathophysiology of asthma has yet to be elucidated, numerous genetic, environmental, and work-related factors contribute to its development.

 Similarly, asthma is a heterogenous disease associated with several clinical phenotypes differentiated by natural history, severity, and response to therapy.

 Phenotypes of severe asthma include allergic asthma, neutrophilic asthma,eosinophilic asthma, and obesity-related asthma.

Inhaled corticosteroids (ICS) are a mainstay of asthma treatment, but even high-dose ICS may not offer sufficient control of severe asthma due to underlying factors.

 Oral corticosteroids (OCS) may be necessary when patients fail to respond to current therapy, experience worsening symptoms, or have exacerbations requiring hospitalization or emergency department visits.

 However, these therapies are associated with serious adverse effects, including psychiatric conditions and disorders of the adrenal glands; the eyes; and the musculoskeletal, cardiovascular, metabolic, and gastrointestinal systems.

Early testing, targeted therapy initiation, and reduced corticosteroid use may be particularly important for younger patients who face a potential lifetime of asthma management. In this article, Dennis K. Ledford, MD, professor of Medicine and Pediatrics and Ellsworth & Mabel Simmons Professor of Allergy and Immunology at the Morsani College of Medicine of the University of South Florida in Tampa, Florida, and Section Chief of Allergy/Immunology at the James A Haley VA Hospital, shares his clinical perspective on severe asthma with an eosinophil phenotype. In particular, he discusses the importance of testing blood eosinophil count during initial disease assessment to personalize therapy selection and reduce corticosteroid use, and he describes effective treatment strategies.

Assessing for the Eosinophilic Phenotype in Severe Asthma

Eosinophils are present in the large airway tissue of up to approximately half to two-thirds of patients with severe asthma.

 Eosinophils are involved in the type 2 immune response, which is associated with severe asthma; this encompasses activation of numerous cell types, including T-helper type 2 (Th2) and innate lymphoid type 2 (ILC2) cells. Exposure to allergens activates Th2 and produces cytokines (interleukin [IL]-4, IL-5, IL-9, and IL-13), resulting in production of immunoglobulin (Ig) E, increased levels of eosinophils, and activation of mast cells. A nonallergic response can also occur in people with severe asthma; it is characterized by the activation of ILC2 cells and the generation of IL-5 and IL-13.

 Regardless of the pathway, IL-5 is the primary cytokine that drives eosinophil growth, differentiation, recruitment, activation, and survival.

As compared to other types of asthma, severe asthma with the presence of eosinophils involves worse asthma symptoms, a lower forced expiratory volume in 1 second (FEV

), and a greater risk for exacerbations and near-death events.

 The International Severe Asthma Registry reported that 74% to 84% of patients with severe asthma most likely had eosinophilic asthma.

 Dr Ledford confirmed, “Individuals who tend to exacerbate the most tend to be eosinophilic.” In patients with severe asthma, regardless of their use of high corticosteroid doses, persistently high levels of eosinophils are more common among individuals with late-onset disease than those with early-onset disease.

 He continued, “If you look at severe eosinophilic asthma, most of those patients seem to start as young adults, and they tend to get a bit worse through their 30s and 40s, then, sometimes, it persists on through life.”

*84% of adults identified as “most likely” to have an eosinophilic phenotype in prospective analysis (N = 1716) using a predefined algorithm of ≥ 1: blood eosinophil count ≥ 300 cells/μL; on anti-IL-5/5R therapy; blood EOS count of ≥ 150-300 cells/μL on maintenance OCS or ≥ 2: nasal polyps, elevated FeNO, late-onset asthma. 74% identified in retrospective analysis of medical records in the United States (n = 1891).

Assessment of risk factors for poor outcomes in asthma is important during the diagnostic process and periodically throughout the disease course.

 The Global Initiative for Asthma (GINA) report states that the presence of type 2 inflammatory markers, such as higher blood eosinophils, are associated with increased risk of asthma exacerbations.

 In patients receiving high-dose ICS or maintenance OCS, markers of type 2 inflammation include a blood eosinophil level of at least 150 cells/μL, a fractional exhaled nitric oxide (FeNO) level of at least 20 ppb, a sputum eosinophil count of at least 2%, and/or asthma that is clinically triggered by allergens.

 To confirm that the asthma does not involve type 2 inflammation, these patients should have their blood eosinophil and FeNO levels checked up to 3 different times, such as when their asthma worsens, before they receive an OCS, or either after their OCS or on their lowest possible dose.

Ledford indicated, “Biomarkers can help us categorize asthma, and they include the presence of allergy, the eosinophil count in the blood, and, sometimes, measuring FeNO from in-office testing. So, with all that information coupled with family history and personal history and current medication use, I can come to a conclusion that it is severe asthma.”

Identifying Patients Who Most Likely Have Eosinophilic Asthma

According to Dr Ledford,“Elevated blood eosinophil counts are so common that I would not hesitate to check a count if an asthma patient was having trouble.” He would also suspect severe eosinophilic asthma in patients who do not experience an adequate response to their maintenance inhalers. He cautioned that hospitalization is not a required defining factor—major interruptions in work and sleep may also suggest this phenotype.

Ledford stated, “There's no real way an individual could tell that they have eosinophilic asthma vs noneosinophilic asthma, other than if their blood eosinophil count is measured. Asthma that's noneosinophilic behaves in a way very similar to that of asthma that's eosinophilic. The big difference is the odds of having severe disease and having exacerbations.” He continued, “Another marker that would make me strongly suspect eosinophilic disease is a coexistence of sinus problems with polyps and asthma.”

Recommended Treatment Approach for Severe Eosinophilic Asthma

“Prednisone or cortisone-like medicines really affect eosinophil biology,” noted Dr. Ledford. “Giving prednisone or systemic steroids to a patient with eosinophilic asthma makes them much better. The problem is that there’s a cumulative adverse effect burden. There are acute effects—patients feel nervous and can’t sleep. These chronic effects such as thinning of the bone, increased risk of cardiovascular problems and weight gain are things that really affect patients' health."

Type 2 inflammation in severe asthma can be unresponsive to high doses of ICS.

 If patients with severe asthma experience exacerbations or suboptimal symptom management despite use of high-dose ICS in combination with long-acting β

-agonists (LABA), phenotypic assessment and referral to a specialist are recommended. Depending on their findings, asthma biologics may be recommended.

Per GINA, asthma biologics, such as NUCALA, are recommended for patients with severe eosinophilic asthma who have experienced exacerbations within the past year and who have blood eosinophil levels of at least 150 cells/μL on recent bloodwork.

NUCALA is an IL-5 antagonist monoclonal antibody (IgG1κ) indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus. Predictors of anti-IL5 therapy efficacy include higher blood eosinophil levels, more exacerbations than in the previous year, onset of asthma in adulthood, and nasal polyposis.

NUCALA targets and binds to IL-5, thus inhibiting IL-5 signaling and reducing the production and survival of eosinophils (

). The mechanism of action of NUCALA in asthma has not been definitively established.

 The mechanism of action of mepolizumab in asthma has not been definitively established.

“NUCALA targets eosinophils and reduces the cells’ activity, but it doesn't eliminate the cells. We think that could be beneficial,” Dr Ledford explained. He acknowledged, “In the majority of patients with allergies who have asthma, severe nonallergen triggers often contribute to the asthma exacerbations. NUCALA also has numerous clinical trials that evaluated reduction in exacerbations, OCS use, and other important measures in severe eosinophilic asthma.”


NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.




Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (ie, days). If a hypersensitivity reaction occurs, discontinue NUCALA.



Acute Asthma Symptoms or Deteriorating Disease


NUCALA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.




In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred with NUCALA compared to none with placebo. Consider vaccination if medically appropriate.




Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.




Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.




In clinical trials in patients receiving NUCALA, the most common adverse reactions (≥5%) were headache, injection site reaction, back pain, and fatigue. Systemic reactions, including hypersensitivity, also occurred. Manifestations included rash, pruritus, headache, myalgia, and flushing; the majority were experienced the day of dosing.


A pregnancy exposure registry monitors pregnancy outcomes in women exposed to NUCALA during pregnancy. To enroll call 



The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.



When testing severe asthma patients for potential biomarkers, clinicians should test for eosinophils multiple times before ruling out severe eosinophilic asthma. Identifying elevated levels of eosinophils in patients soon after a diagnosis of severe asthma can help guide targeted treatment selection, and it may be particularly helpful in treating patients with severe disease that has been refractory to standard therapies.

 We hope to have more data on long-term outcomes and real-world data with asthma biologics to guide asthma management. “If you have therapeutics that can help make a difference, like NUCALA, you should explore those options,” Dr Ledford stated. “Patients with severe eosinophilic asthma have lived with it, sometimes, for decades. They just think that it's normal, and they accept it. And it's unfortunate, because we have so many good therapeutic options now.”

Advertorial intended for US healthcare professionals only.

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Articles

The Importance of Phenotype Testing in Severe Asthma

Psoriatic arthritis (PsA) is a clinically heterogeneous, chronic, and progressive immune-mediated disease that develops in up to 30 percent of patients with psoriasis and is characterized by a form of inflammation, which can include both the skin and joints.

 Around 1.5 million people in the United States are currently living with PsA, and common delays in diagnosis and treatment can lead to worse functional outcomes.

 Given that active PsA presents differently in each patient in terms of disease extent, severity, and response to therapy, healthcare professionals face several diagnosis and disease management challenges.

Here are some key considerations to keep in mind when working with patients to navigate this chronic condition and implement treatment strategies to help improve active PsA symptoms.

“Despite the prevalence of active PsA in the U.S. and our understanding of the disease, underdiagnosis and, subsequently, undertreatment of patients remains a challenge,”

 said Dr. Soumya Chakravarty, MD, PhD, Senior Director, Strategic Lead, Rheumatology Therapeutic Area, at The Janssen Pharmaceutical Companies of Johnson & Johnson.

To help ensure early detection of active PsA, healthcare professionals in primary care and dermatology settings are encouraged to proactively screen patients with psoriasis for signs of active PsA with multiple, validated screening questionnaires currently available for use in clinical practice.

 The Classification Criteria for Psoriatic Arthritis (CASPAR criteria), which were developed to classify patients with active PsA in clinical studies, have served as a helpful tool for clinicians in confirming the diagnosis of active PsA.

 The CASPAR criteria use a point-scoring system based on symptoms, personal and family history of psoriasis, and radiographic evidence of new bone formation, highlighting the importance of the history of disease and the association between active PsA and psoriasis.

“The CASPAR criteria can help confirm the diagnosis of active PsA after professionals in primary care and dermatology settings refer patients to a rheumatologist if they have three or more points in the CASPAR criteria categories,”

 said Dr. Chakravarty. “It is worth noting, however, that these tools do not provide complete certainty, which is why regular screenings are suggested in patients with psoriasis.”

In addition to using diagnostic criteria to assess the severity of active PsA, rheumatologists and dermatologists are also building appropriate treatment plans based on outcomes for each individual patient.

 Various treatments are available to patients to address a range of symptoms such as inflammation, stiffness, and pain, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and biologics.

 Furthermore, some biologic agents have clinical evidence around improving symptoms of fatigue.

 Because of this, it is important that rheumatologists and dermatologists remain in contact throughout a patient’s journey to ensure they are responding to treatment depending on symptoms and their severity.

Common symptoms of active PsA include joint pain, stiffness, and symptoms of dactylitis, enthesitis, and axial disease.

 However, there are other symptoms, such as fatigue, that may present differently from patient to patient.

 “Despite being a common concern for patients, fatigue is unfortunately often underestimated and misunderstood,”

 said Dr. Chakravarty. “And, although it can be subjective, fatigue is a medical symptom that can be a challenge for patients and interfere with daily activities, so it’s important for providers to consider it when making treatment decisions.”

Many patients may feel disappointed by how the disease impacts their ability to do daily tasks or how they are responding to treatment. That is why it is important for patients and providers to have an open dialogue about what is and is not working to tailor a treatment plan to meet specific needs, which can include nonpharmacological strategies like improving nutrition and physical exercise, and seeking support groups.

 This individualized approach to care should also recognize the personal circumstances and environment of each patient to help ensure their treatment plan fits their lifestyle and can be implemented within different family, work, and cultural dynamics. And lastly, because active PsA is a progressive disease, and its severity can vary from patient to patient, it is important to help patients understand that it can take time to develop an appropriate treatment plan, and recognize it is not a failure if adjustments need to be made over time.

Evaluating Biologic Therapy as a Potential Treatment Option

The introduction and continued development of biologic therapies as a treatment option represents an important development for healthcare professionals treating active PsA and has helped generate improvement in disease symptoms.

“With differences in disease extent, severity and treatment response from patient to patient, it’s important that healthcare providers have access to biologic therapies that can help reduce the burden of active psoriatic arthritis,”

 said Dr. Chakravarty. “Biologics target specific cells in the immunologic pathway of inflammation to help improve symptoms that impact daily living, like joint pain, stiffness, and swelling that make everyday tasks harder to do.”

As the treatment landscape for active PsA continues to evolve and patients remain in need of additional therapeutic options, rheumatologists should evaluate each patient’s active PsA individually and consider whether starting a biologic therapy at an early stage in their journey would be appropriate.

 One biologic therapy that is available today is TREMFYA® (guselkumab), a prescription medicine used to treat adults with active PsA.

 It is the first and only FDA-approved, fully human selective anti-IL-23 therapy for adults with active PsA.

Two pivotal phase 3 multicenter, randomized, double-blind, placebo-controlled studies, DISCOVER 1 and DISCOVER 2, evaluated the efficacy and safety of TREMFYA® administered as 100 mg subcutaneous injections in adults with active PsA who had an inadequate response to standard therapies, including NSAIDs and DMARDs; patients in the DISCOVER 1 trial may have been previously treated with up to two anti-tumor necrosis factor alpha (TNFα) inhibitors, a biologic therapy, while patients in the DISCOVER 2 trial were biologic treatment naïve.

The results showed that a significant percentage of patients treated with TREMFYA® reached the studies’ primary endpoint of ACR20

 at 24 weeks (52% and 64%), compared to patients treated with placebo (22% and 33%) in DISCOVER 1 and DISCOVER 2, respectively.

In addition, treatment with TREMFYA® resulted in an improvement in the skin manifestations of psoriasisin patients with active PsA, an improvement in dactylitis and enthesitis, and an improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F).

In the 24-week, placebo-controlled period of the combined DISCOVER 1 and DISCOVER 2 clinical trials, the overall safety profile observed in patients with active PsA treated with TREMFYA® was generally consistent with the profile in patients with plaque psoriasis with the addition of bronchitis and neutrophil count decreased.

 In the 24-week, placebo-controlled period, combined across the 2 studies:

Bronchitis occurred in 1.6% of patients in the TREMFYA® q8w group and 1.1% of patients in the placebo group

Neutrophil count decreased occurred in 0.3% of patients in the TREMFYA® q8w group compared to 0% of patients in the placebo group. The majority of events of neutrophil count decreased were mild, transient, not associated with infection and did not lead to discontinuation

Results may vary. TREMFYA® is not right for everyone. Click 

 for more information to help determine if TREMFYA® may be right for your adult patients with active PsA.

TREMFYA® is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients. Serious hypersensitivity reactions, including anaphylaxis, have been reported. TREMFYA® may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a clinically important or serious infection develops, discontinue TREMFYA® until the infection resolves. Evaluate for tuberculosis before treating with TREMFYA®. Avoid use of live vaccines in patients treated with TREMFYA®. Please see related and other Important Safety Information below.

Continuing Patient Support Along the Treatment Journey

Support programs can be an important resource for both patients and healthcare providers to help ease some of the challenges patients face when starting and staying on treatment. For example, if a patient has been prescribed TREMFYA® for approved on-label use and is 18 or older, they are eligible for the TREMFYA withMe program.* TREMFYA withMe provides a range of dedicated support to help make it easier for patients as they begin, and continue, their TREMFYA® treatment journey. At the core of the program is a TREMFYA withMe Guide, a dedicated and qualified healthcare professional† who can work one-on-one with patients to answer questions about prescription fulfillment and cost support, connect patients to injection support, help with treatment expectations, and provide regular updates and reminders at the patient’s request.

TREMFYA withMe is limited to education for patients about TREMFYA®, its administration, and/or their disease, and is not intended to provide medical advice, replace a treatment plan from the patient’s doctor or nurse, or provide case management services.

*For those eligible, TREMFYA withMe is completely free. Eligibility for program components may vary.


TREMFYA® is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients.


Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of TREMFYA®. Some cases required hospitalization. If a serious hypersensitivity reaction occurs, discontinue TREMFYA® and initiate appropriate therapy


TREMFYA® may increase the risk of infection. Treatment with TREMFYA® should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated.

Consider the risks and benefits of treatment prior to prescribing TREMFYA® in patients with a chronic infection or a history of recurrent infection. Instruct patients receiving TREMFYA® to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection, or is not responding to standard therapy, closely monitor and discontinue TREMFYA® until the infection resolves.

Pre-Treatment Evaluation for Tuberculosis (TB)


Evaluate patients for TB infection prior to initiating treatment with TREMFYA®. Initiate treatment of latent TB prior to administering TREMFYA®. Monitor patients for signs and symptoms of active TB during and after TREMFYA® treatment. Do not administer TREMFYA® to patients with active TB infection.


Prior to initiating TREMFYA®, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TREMFYA®.


Most common (≥1%) adverse reactions associated with TREMFYA® include upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.

The overall safety profile observed in patients with psoriatic arthritis is generally consistent with the safety profile in patients with plaque psoriasis, with the addition of bronchitis and neutrophil count decreased.

 for TREMFYA®. Provide the Medication Guide to your patients and encourage discussion.


TREMFYA® is indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

TREMFYA® is indicated for the treatment of adults with active psoriatic arthritis.

DISCOVER-1 and DISCOVER-2 were two phase 3, multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of TREMFYA® administered q8w subcutaneously after starter doses at Week 0 and Week 4 (n=127 and n=248, respectively) or placebo (n=126 and n=246, respectively), with starter doses at Week 0 and then every 4 weeks in patients with active PsA (fulfilling ClASsification criteria for Psoriatic ARthritis [CASPAR]) despite standard therapies (nonbiologic DMARDs, apremilast, and NSAIDs. A stable dose of 1 selected nonbiologic DMARD, corticosteroids, and NSAIDs was permitted but not required. In DISCOVER-1, eligible patients (≥18 years of age) had active PsA (swollen/tender joints ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) for at least 6 months and included patients with prior biologic experience of ≤2 anti-TNFα treatments. Patients with other inflammatory diseases and those who had previously received Janus kinase (JAK) inhibitors or biologics other than TNFα inhibitors were excluded. In DISCOVER-2, eligible patients (≥18 years of age) had active PsA (swollen/tender joints ≥5, CRP ≥0.6 mg/dL) for at least 6 months and no prior JAK inhibitor or biologic experience. At Week 16, patients in all treatment groups who had <5% improvement from baseline in both swollen and tender joint counts were considered as meeting early escape and were allowed to initiate or increase the dose of one of the permitted concomitant medications up to the maximum dose allowed. The primary endpoint in DISCOVER-1 and DISCOVER-2 was ACR20 response at Week 24.

a. ACR20=American College of Rheumatology 20% improvement criteria.

b. Functional Assessment of Chronic Illness Therapy –Fatigue (FACIT-F) Scale: measured on a 4-point Likert scale (4 = not at all fatigued to 0 = very much fatigued).

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TREMFYA® (guselkumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

Nowell WB, Gavigan K, Kannowski CL, et al. Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower. 

 23, 53 (2021). https://doi.org/10.1186/s13075-021-02430-0

Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W. Fatigue - an underestimated symptom in psoriatic arthritis. 

. 2017;55(3):125-130. doi:10.5114/reum.2017.68911

Creaky Joints. Psoriatic arthritis and mental health: Link to depression, anxiety, fatigue. Accessed September 26, 2022. 

https://creakyjoints.org/about-arthritis/psoriatic-arthritis/psa-treatment/psoriatic-arthritis-mental-health/

D'Angelo S, Tramontano G, Gilio M, Leccese P, Olivieri I. Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders. 

. 2017 Mar 2;9:21-28. doi: 10.2147/OARRR.S56073. PMID: 28280401; PMCID: PMC5338946.

Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis (DISCOVER 2): a double-blind, randomized, placebo-controlled phase 3 trial. 

Singh JA, Guyatt G, Ogdie A, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. 

2019 Jan;71(1):5-32. doi: 10.1002/art.40726. PMID: 30499246; PMCID: PMC8218333.

McInnes I, Sawyer LM, Markus K, et al. Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesities and dactylitis outcomes. 

. 2022;8:e002074. doi:10.1136/rmdopen-2021-002074

Boehncke WH, Brembilla NC, Nissen MJ. Guselkumab: the first selective IL-23 inhibitor for active psoriatic arthritis in adults. 

. 2021 Jan;17(1):5-13. doi: 10.1080/1744666X.2020.1857733. PMID: 33251833.

Deodhar A, Helliwell PS, Boehncke WH, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naïve or had previously received TNFα inhibitor treatment (DISCOVER 1): a double-blind, randomised, placebo-controlled phase 3 trial. 

Nash P, McInnes I, Ritchlin CT, et al. AB0525 Guselkumab treatment shows rapid onset of effect on components of American College of Rheumatology response criteria: results of 2 randomized phase 3 trials. 

 Janssen Biotech, Inc. 2022 11/22 cp-343015v1

Kavanaugh A, Helliwell P, Ritchlin CT.l. Psoriatic arthritis and burden of disease: patient perspectives from the population-based multinational assessment of psoriasis and psoriatic arthritis (MAPP) survey. 

 Janssen Biotech, Inc. 2022 10/22 cp-343015v1

Building Patient-Centric Management Plans to Help Improve Symptoms for People with Active Psoriatic Arthritis

Globally, an estimated 850 million and 64 million people live with some form of kidney disease and heart failure (HF), respectively. Patients with chronic conditions of HF, chronic kidney disease (CKD), and diabetes, as well as those taking certain medications like RAAS inhibitors, are at an increased risk of developing hyperkalemia (HK) - a higher-than-normal potassium level in the blood.

HK can be a chronic condition and has been associated with increased hospitalizations and death. In a US-based retrospective study from integrated health delivery networks, HK was found to be an independent risk factor for all-cause mortality in almost 1 million patients including those with CKD, HF, and/or diabetes.

 In a second US-based retrospective analysis of a medical claims database of 39,626 matched pairs of patients with or without HK, 40% of patients with HK experienced 2 or more hyperkalemic events during the 1-year post index period.

“It is important to take hyperkalemia seriously, as it is a potentially fatal condition,” says Pamela Kushner, MD, FAAFP, a primary care physician (PCP) and clinical professor at the University of California Irvine Medical Center. “People with CKD, and/or HF, or other cardio-renal comorbidities, if they are diagnosed with chronic hyperkalemia, they may need long-term management due to the underlying condition. As a PCP, I often support my patients with a diagnosis of hyperkalemia, and I make regular potassium monitoring a part of their long-term care plans as soon as possible.”

RAASi therapy are a group of medicines recommended by the 2021 European Society of Cardiology (ESC) and the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) for the treatment of patients with HF. The 2022 and 2021 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines recommend the use of ACEi or ARB for the treatment of patients with CKD and hypertension with/or without diabetes.

Javed Butler, MD, MPH, MBA, a cardiologist at Baylor Scott and White Health in Dallas, Texas, and a professor of medicine at the University of Mississippi Medical Center in Jackson, Mississippi, explains, “RAASi therapy is one of the most important management approaches for HF patients. These lifesaving treatments reduce the number of HF-related hospitalizations and reduce mortality risk.”

Unfortunately, RAASi therapy has been associated with HK, which is often treated with a reduction or discontinuation of RAASi therapy. In a US-based medical records analysis of patients prescribed a RAASi, including ACE inhibitors, ARBs, direct renin inhibitors and select MRAs, mortality was at least 2x higher for patients with CKD whose RAASi had been reduced (20.3%) or discontinued (22.4%) compared to patients on maximum RAASi doses (9.8%).

Given the impact that HK can have on patients, a long-term and continued approach to treating HK is needed.

 diet is a non-therapeutic approach to managing HK, however, there is a lack of high-quality evidence demonstrating its effectiveness as a HK management strategy. A major contributor to HK in patients with advanced CKD is inadequate excretion of K

 through the kidneys, so reduction in dietary K

 alone may not be sufficient. In addition, a low K

 diet may deprive patients of important nutrients or could conflict with some aspects of a heart-healthy diet. Dietary modifications can be challenging to achieve and adhere to in patients with CKD as well.

There are several guideline recommended options for managing HK which include both therapeutic and non-therapeutic approaches.

According to one practice point from the 2021 KDIGO clinical practice guidelines for the management of blood pressure in CKD, HK associated with RASi use can often be managed by measures to reduce the serum K

 levels rather than decreasing dose or stopping RASi. Strategies to control chronic HK include dietary potassium restriction; discontinuation of potassium supplements, certain salt substitutes, and hyperkalemic drugs; adding potassium-wasting diuretics; and oral potassium binders. In CKD patients receiving RASi who develop HK, the latter can be controlled with newer oral K

 binders in many patients, with the effect that RASi can be continued at the recommended dose.

The 2022 KDIGO Clinical Practice Guideline for Diabetes Management in CKD recommends that treatment with an ACEi or ARB be initiated in patients with diabetes, hypertension, and albuminuria, and that these medications be titrated to the highest approved dose that is tolerated. Hyperkalemia associated with the use of an ACEi or ARB can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the ACEi or ARB immediately. Measures to manage HK include: review concurrent drugs including over the counter and herbal drugs as well as supplements to avoid/discontinue drugs that impair K

 excretion, moderate potassium intake, and consider diuretics, sodium bicarbonate, and potassium binders. Potassium binders should be considered to decrease serum K

 levels after other measures have failed, rather than decreasing or discontinuing ACEi or ARB treatment.

Among patients with HF, the ESC 2021 guideline refers to the use of potassium binders for the treatment of acute and chronic HK in patients with HF which may allow initiation or uptitration of RAASi in patients with renal dysfunction or HK.

Rethinking Episodic Hyperkalemia Management in Support of Current Guideline Recommendations

HK can present as a single episode, but the reality for many patients with CKD is that their HK will, or already has, become a chronic condition. HK remains an ongoing threat in patients with comorbidities such as HF, CKD, and/or diabetes, as many within this patient population have recurrent HK episodes.

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