You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.
 

CME / ABIM MOC / CE

Are All Biologics Used in Asthma the Same?

  • Authors: News Author: Pam Harrison; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 8/26/2022
  • Valid for credit through: 8/26/2023
Start Activity

  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0.25 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for pulmonologists, allergists/clinical immunologists, family medicine/primary care clinicians, internists, pediatricians, nurses, pharmacists, physician assistants, and other members of the health care team for patients with severe eosinophilic asthma.

The goal of this activity is for learners to be better able to describe the safety and efficacy of the monoclonal antibodies mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma.

Upon completion of this activity, participants will:

  • Assess the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma, based on a systematic review and network meta-analyses
  • Evaluate the clinical implications of the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma, based on a systematic review and network meta-analyses
  • Outline implications for the healthcare team


Disclosures

Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated according to Medscape policies. Others involved in the planning of this activity have no relevant financial relationships.


News Author

  • Pam Harrison

    Freelance writer, Medscape

    Disclosures

    Pam Harrison has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.


Accreditation Statements



In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

    For Physicians

  • Medscape, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

    Contact This Provider

    For Nurses

  • Awarded 0.25 contact hour(s) of nursing continuing professional development for RNs and APNs; 0.25 contact hours are in the area of pharmacology.

    Contact This Provider

    For Pharmacists

  • Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number: JA0007105-0000-22-275-H01-P).

    Contact This Provider

  • For Physician Assistants

    Medscape, LLC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credits. Approval is valid until 8/26/2023. PAs should only claim credit commensurate with the extent of their participation.

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 75% on the post-test.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.

CME / ABIM MOC / CE

Are All Biologics Used in Asthma the Same?

Authors: News Author: Pam Harrison; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 8/26/2022

Valid for credit through: 8/26/2023

processing....

Clinical Context

Although less than 10% of individuals with asthma have severe disease, these account for most asthma-related morbidity and mortality. Since 2003, several biologic agents targeting various interleukin signaling pathways have been available for those with severe disease.

In placebo-controlled trials, mepolizumab, benralizumab, and dupilumab have been shown to reduce exacerbation rates, improve lung function, and improve quality of life among individuals with severe eosinophilic asthma (SEA). Bayesian network meta-analyses allows simultaneous comparisons of these treatments, rather than pairwise comparisons, and generation of a probability-based ranking of their safety and efficacy.

Study Synopsis and Perspective

Differences in the safety and efficacy between the biologics approved for the treatment of severe eosinophilic asthma are so minimal as to not meet clinically important thresholds, a network meta-analysis shows.

"We know relatively little of the comparative effectiveness or safety of biologics approved for the treatment of asthma [but since] the number of these biologics continue to rise--and their indications are increasing--the opportunities to use these biologics will only continue to increase, and we need to know more about their comparative effectiveness to optimize their use," Ayobami Akenroye, MD, MPH, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, told Medscape Medical News in an email.

"But the decision to use one biologic or not is complex and goes beyond comparative effectiveness, and factors such as insurance coverage, convenience of self-administration, and comorbidities all play a role in the choice of biologics," she said. She noted that all the outcomes assessed in the study contribute to or reflect a patient's underlying asthma control.

The study was published online June 27 in the Journal of Allergy and Clinical Immunology.

Interleukin Pathways

Drugs that target various interleukin signaling pathways involved in the pathogenesis of asthma include mepolizumab, benralizumab, and dupilumab, all of which have been shown to decrease exacerbation rates, improve lung function, and enhance quality of life for patients with severe eosinophilic asthma. In a Bayesian network meta-analysis that allows for simultaneous comparisons of these 3 treatments, investigators analyzed 8 randomized, placebo-controlled trials that compared each of the drugs with placebo. In total, the trials involved 6461 patients; the duration of follow-up was between 24 and 56 weeks.

"In the subgroup of patients with eosinophil counts of ≥300 cells/mcL, all three biologics were significantly better than placebo in reducing exacerbations," Dr Akenroye and colleagues report. For example, dupilumab reduced the exacerbation risk by 68% at a risk ratio (RR) of 0.32 (95% credible interval [CI], 0.23-0.45), whereas mepolizumab reduced it by almost as much, at 63% (RR, 0.37; 95% CI, 0.30-0.45).

Benralizumab was slightly less effective than the other 2 biologics, reducing exacerbation risk by 51% (RR, 0.49; 95% CI, 0.43-0.55). "In patients with eosinophil counts of ≥300 cells/mcL, all three biologics had a probability of 1 in improving the exacerbation rate by 20% or more. . .in comparison to placebo," the authors emphasize.

Regarding each drug's effect in improving forced expiratory volume in 1 second (FEV1), the mean difference in milliliters (MD) with dupilumab before and after treatment was 230 (95% CI, 160-300), whereas for benralizumab, the MD was 150 (95% CI, 100-220) before and after treatment. With mepolizumab, the MD in FEV1 before and after treatment was also 150 (95% CI, 66-220). In the same subgroup of patients with eosinophil counts of at least 300 cells/μL, all 3 biologics again had a probability of 1 in improving FEV1 by 50 mL or more above the placebo effect. A third endpoint that was analyzed was the potential reduction in Asthma Control Questionnaire (ACQ) scores. With mepolizumab, the MD before and after treatment was −0.65 (95% CI, −0.81 to −0.45), with dupilumab it was −0.48 (95% CI, −0.83 to −0.14), and with dupilumab it was −0.32 (95% CI, −0.43 to −0.21).

"Dupilumab was significantly better than benralizumab in improving exacerbations," the authors note (RR, 0.66; 95% CI, 0.47-0.94), whereas mepolizumab was also better than benralizumab (RR, 0.75; 95% CI, 0.60-0.95). In contrast, both dupilumab and benralizumab led to greater improvements in FEV1 than mepolizumab, although the effects of dupilumab and benralizumab on ACQ scores were not significantly different for patients whose lower eosinophil counts were between 150 and 299 cells/μL.

As for safety outcomes, both mepolizumab and benralizumab were associated with a lower risk for serious adverse events, but dupilumab was not different from placebo in terms of overall safety, according to the authors.

"[However], these results may be helpful to clinicians as they optimize patient care," they conclude. Limitations to the analysis include the fact that indirect comparisons cannot replace randomized trials that compare the 3 drugs directly.

Dr Akenroye has disclosed no relevant financial relationships.

J Allergy Clin Immunol. Published online June 27, 2022.[1]

Study Highlights

  • Bayesian NMA included 8 randomized clinical trials (n=6,461) of biologics for SEA identified from systematic review of peer-reviewed literature from 2000 to 2021.
  • In individuals with at least 300 eosinophils per microliter (eosin/μL), RRs for exacerbation rates vs placebo were 0.32 for dupilumab (95% CI, 0.23-0.45), 0.37 for mepolizumab (95% CI, 0.30-0.45), and 0.49 for benralizumab (95% CI, 0.43-0.55).
  • For improving FEV1, MDs were 230 milliliters for dupilumab (95% CI, 160-300), 150 for benralizumab (95% CI, 100-200), and 150 for mepolizumab (95% CI, 66-220).
  • For reducing ACQ, MDs were −0.63 for mepolizumab (95% CI, −0.81 to −0.45), −0.48 for dupilumab (95% CI, −0.83 to −0.14), and −0.32 for benralizumab (95% CI, −0.43 to −0.21).
  • In individuals with eosinophil counts of 150 to 299 eosin/μL, benralizumab (RR, 0.62; 95% CI, 0.52-0.73) and dupilumab (RR, 0.60; 95% CI, 0.38-0.95) were linked to lower exacerbation rates; only benralizumab (MD, 81; 95% CI, 8-150) significantly improved FEV1.
  • Compared with clinically important thresholds, these differences were minimal.
  • In the overall population, odds of serious adverse events (SAE) were lower for mepolizumab (OR, 0.67; 95% CI, 0.48-0.92) and benralizumab (OR, 0.74; 95% CI, 0.59-0.93), but no different from placebo for dupilumab (OR, 1.0; 95% CI, 0.74-1.4).
  • The investigators concluded that in SEA, efficacy and safety differences among mepolizumab, benralizumab, and dupilumab were minimal, based on low to moderate certainty of evidence from only 8 eligible placebo-controlled trials identified, leading to a sparse network with no direct head-to-head trials.
  • All 3 biologics were associated with significant improvement of exacerbation rates compared with placebo, but relative ranking of the treatments varied, based on eosinophil thresholds.
  • Effects on exacerbations, FEV1, and ACQ were similar for all 3 agents, and differences in exacerbation rates, FEV1, and ACQ did not meet clinically important thresholds (≤5% probability that any of these biologics would halve the exacerbation rate compared with another biologic).
  • Considering SAEs and exacerbation rates together and SAEs and FEV1 together, mepolizumab and benralizumab had a higher Surface Under the Cumulative Ranking (SUCRA) value than dupilumab in both subgroups based on eosinophil count, but overall differences were minimal.
  • There is ample evidence supporting a dose-response relationship between blood eosinophil count and the efficacy of mepolizumab, benralizumab, and dupilumab, with individuals with higher eosinophil counts experiencing greater benefits when compared with placebo.
  • Benralizumab was particularly effective in individuals with an eosinophil count of 150 to 299 cells/μL, but differences between biologics were not statistically significant.
  • This may be related to interleukin-5 receptor blockade, which usually causes near-complete eosinophil depletion.
  • Some patients may prefer self-administration, first approved for dupilumab but now approved for all 3 biologics, or bimonthly dosing of benralizumab vs monthly dosing of mepolizumab or biweekly dosing of dupilumab.
  • Study limitations include inability of indirect comparisons to replace randomized trials directly comparing these 3 drugs and use of aggregated data, which limit applicability of the findings to individual patients.
  • In addition, findings from randomized placebo-controlled trials may not be representative of real-world populations.

Clinical Implications

  • In SEA, efficacy and safety differences among mepolizumab, benralizumab, and dupilumab were minimal.
  • The study findings offer valuable information for clinicians and patients to help balance safety and efficacy of these biologics.
  • Implications for the Health Care Team: The ultimate choice of biologic for each patient depends on multiple factors including cost considerations, insurance coverage, and timing of administration. A team approach should be taken when selecting the most appropriate biologic.

 

Earn Credit