Antibodies

This monoclonal antibody that blacks the inflammatory response to both neutrophils and eosinophils appears to improve health-related quality of life and reduce moderate to severe exacerbations in people with COPD. However, it may not be available yet and is probably going to be very expensive when it is available.

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Rationale
The efficacy and safety of astegolimab, an anti-ST2 monoclonal antibody, was evaluated in participants with chronic obstructive pulmonary disease (COPD) and frequent exacerbations in the pivotal ALIENTO and ARNASA trials.

Objectives
To report the prespecified pooled analysis of ALIENTO and ARNASA.

Methods
ALIENTO and ARNASA were randomized, double-blind, placebo-controlled trials with similar designs and included participants with COPD, a history of frequent exacerbations, and current/former smoking status, irrespective of blood eosinophil count and chronic bronchitis. Participants were randomized 1:1:1 to astegolimab 476 mg every 2 weeks (Q2W), astegolimab every 4 weeks (Q4W), or placebo for 52 weeks, plus optimized maintenance therapy. The primary endpoint was annualized rate of moderate/severe exacerbations. Secondary endpoints included annualized rate of severe exacerbations. A hierarchical statistical plan was followed with hypothesis testing of secondary efficacy endpoints gated on the primary efficacy endpoint success.

Measurements and Main Results
A total of 2682 participants were included in the pooled intent-to-treat population. Astegolimab significantly reduced the annualized rate of moderate/severe exacerbations by 15% in the Q2W arm (adjusted rate ratio, 0.85 [95% CI, 0.76-0.96]; P = .0077) and by 12% in the Q4W arm (rate ratio, 0.88 [95% CI, 0.78-0.99]; P = .0265). A nominally significant reduction in the annualized rate of severe COPD exacerbations (rate ratio, 0.68 [95% CI, 0.52-0.87]; P = .0028) was observed for astegolimab Q2W vs placebo. Astegolimab was well tolerated.

Conclusions
Astegolimab every 2 weeks reduced the annualized rate of moderate/severe exacerbations in a clinically heterogeneous population of participants with COPD and frequent exacerbations.

Clinical trial registration
ClinicalTrials.gov: NCT05037929; NCT05595642

Author/s:

Jadwiga A Wedzicha, Alvar Agustí, Christopher E. Brightling, Peter Calverley, James D. Chalmers, Neil J. Greening, MeiLan K. Han, Divya Mohan, Julie Ng, Papi, Alberto, Nicolas Roche, Rebecca Saenz, Katerina Samara, Ruth Tal-Singer, Claus F. Vogelmeier, Xiaoying Yang, Bartolome R. Celli

Treatment of Atopic Dermatitis

Megan George — Thu, 21 Aug 2025 15:59:01 +0000

Date Added:

August 21, 2025

Journal/Publication:

JAMA

Publication Date:

August 20, 2025

URL:

Treatment of Atopic Dermatitis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.11589

Keywords

dermatology

atopic dermaitis

A review of currently available treatment methods for patients with atopic dermatitis. James W. Mold, MD, MPH

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Author/s:

Aaron M. Drucker

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

Alex Haga — Sun, 30 Jun 2024 18:27:10 +0000

Date Added:

June 30, 2024

Journal/Publication:

New England Journal of Medicine

Publication Date:

May 20, 2024

Issue:

Volume:

390

URL:

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2401304

Keywords

PMID (1):

38767614

MeSH

Antibodies

Monoclonal

Humanized* / adverse effects

Humanized* / therapeutic use

Eosinophils*

Forced Expiratory Volume / drug effects

Inflammation

Leukocyte Count

Pulmonary Disease

Chronic Obstructive* / blood

Dupilumab (Dupixent) appears to reduce exacerbations and improve FEV1 in patients with COPD with elevated blood eosinophil counts. James W. Mold, MD, MPH

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Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.

Methods: In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George's Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52.

Results: A total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P = 0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab.

Conclusions: In patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo.

Author/s:

Surya P Bhatt, Klaus F Rabe, Nicola A Hanania, Claus F Vogelmeier, Mona Bafadhel, Stephanie A Christenson

Ulcerative Colitis in Adults: A Review

Rowan Hutchins — Tue, 03 Oct 2023 05:00:00 +0000

Date Added:

October 3, 2023

Journal/Publication:

JAMA

Publisher:

AMA

Publication Date:

September 12, 2023

Issue:

Volume:

330

Pages:

951-965

URL:

Ulcerative Colitis in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2023.15389

Keywords

ulcerative colitis

Mesalamine

quality of life

PMID (1):

37698559

MeSH

Antibodies

Anitbodies, Monoclonal

Colitis

Ulcerative* / complications

Ulcerative* / diagnosis

Colorectal Neoplasms* / diagnosis

Colorectal Neoplasms* / epidemiology

A review of ulcerative colitis in adults. James W. Mold, MD, MPH

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Importance: Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, with a prevalence exceeding 400 per 100 000 in North America. Individuals with UC have a lower life expectancy and are at increased risk for colectomy and colorectal cancer.

Author/s:

Gros, Beatriz, Kaplan, Gilaad

Migraine — Treatment and Preventive Therapies

Aubrey Delammermore — Thu, 13 Oct 2022 05:00:00 +0000

Date Added:

October 13, 2022

Journal/Publication:

New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

October 13, 2022

Issue:

e35

Volume:

387

URL:

Migraine — Treatment and Preventive Therapies

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Video

DOI (1):

10.1056/NEJMp2212749

Keywords

migraine treatment

preventative therapies

injectable monoclonal antibodies

patient care

treatment

MeSH

Patient-Centered Care

An 11 minute video review of our current understanding of migraine and an update on newer therapies. James W. Mold, MD, MPH

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In this instructional video, Drs. Cynthia Armand and Elizabeth Loder discuss the clinical presentation and pathophysiology of migraine and treatment options for patients.

This video provides essential and useful information for any clinician caring for patients with this common condition. Newer acute and preventive therapies — including triptans, gepants, ditans, and injectable monoclonal antibodies — are discussed, as are the importance of a patient-centered approach and the need to tackle challenges of access to these newer agents.

Author/s:

Armand, C.E., Loder, E., Ropper, A. H.

Rickettsial Disease Diagnostic Testing and Interpretation

Saige Blanchard — Fri, 28 May 2021 05:00:00 +0000

Date Added:

May 28, 2021

Publisher:

Centers for Disease Control and Prevention

Publication Date:

May 25, 2021

URL:

Rickettsial Disease Diagnostic Testing and Interpretation

Type:

Clinical Decision Aids, Public Health Announcements

Format:

Video

Keywords

MeSH

Polymerase Chain Reaction

Rickettsia Infections

Antibodies

health personnel

Fluorescent Antibody Technique, Indirect

A 10 minute you-tube video discussing current testing recommendations for Rickettsial diseases. James W. Mold, MD, MPH

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This video provides information on rickettsial disease diagnostic methods for healthcare providers, including what tests are available and when it is most appropriate to collect samples. This video focuses on the use of polymerase chain reaction (or PCR) tests, and the indirect immunofluorescence antibody (IFA) assay for rickettsial disease diagnosis.

Author/s:

Centers for Disease Control and Prevention

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

Devin Evans — Thu, 14 Jan 2021 06:00:00 +0000

Date Added:

January 14, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

December 17, 2020

URL:

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1056/NEJMoa2035002

Keywords

PMID (1):

33332778

MeSH

A review of what is currently known about the monoclonal antibody cocktail for outpatient treatment of COVID-19. James W. Mold, MD, MPH

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Background: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

Methods: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change from baseline in viral load from day 1 through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients.

Results: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group.

Conclusions: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group.

Author/s:

Weinreich, David M., Sivapalasingam, Sumathi, Norton, THomas,, Ali, Shazia, Gao, Haitao, Bhore, Rafia, Musser, Bret J., Soo, Yuhwen, Rofail, Diana, Im, Joseph, Perry, Christina, Pan, Cynthia, Hosain, Romana, Mahmood, Adnan, Davis, John D., Turner, Kenneth C., Hooper, Andrea T., Hamilton, Jennifer D., Baum, Alina, Kyratsous, Christos A., Kim, Yunji, Cook, Amanda, Kampman, Wendy, Kohli, Anita, Sachdeva. Yessica, Graber, Ximena, Kowal, Bari, DiCioccio, Thomas, Stahl, Neil, Lipsich, Leah, Braunstein, Ned, Herman, Gary, Yancopoulos, George D.

Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Devin Evans — Wed, 28 Oct 2020 05:00:00 +0000

Date Added:

October 28, 2020

Journal/Publication:

British Medical Journal

Publication Date:

October 22, 2020

Issue:

371

URL:

Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1136/bmj.m3939

Keywords

PMID (1):

33093056

MeSH

Based upon this RCT, once a COVID-19 patient is hospitalized, treatment with convalescent plasma apparently has little effect on outcomes. James W. Mold, MD, MPH

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Abstract

Objective To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India.

Design Open label, parallel arm, phase II, multicentre, randomised controlled trial.

Setting 39 public and private hospitals across India.

Participants 464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm).

Interventions Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study.

Main outcome measure Composite of progression to severe disease (PaO2/FiO2 <100 mm Hg) or all cause mortality at 28 days post-enrolment.

Results Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval −0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54).

Conclusion Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19.

Trial registration Clinical Trial Registry of India CTRI/2020/04/024775.

Author/s:

Agarwal, Anup, Mukherjee, Aparna, Kumar, Gunjan, Chatterjee, Pranab, Bharnagar, Tarun, Malhotra, Pankaj

SARS-CoV-2 (COVID-19) serology: implications for clinical practice, laboratory medicine and public health

Brian Desmarais — Mon, 10 Aug 2020 17:58:44 +0000

Date Added:

August 10, 2020

Journal/Publication:

Canadian Medical Association Journal

Publication Date:

August 3, 2020

URL:

SARS-CoV-2 (COVID-19) serology: implications for clinical practice, laboratory medicine and public health

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.201588

MeSH

severe acute respiratory syndrome coronavirus 2

COVID-19

Serologic Tests

Antibodies

A nice review of serological tests for COVID-19 antibodies and recommendations for when to and when not to use them. James W. Mold, MD, MPH

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Not available.

Author/s:

Caeseele, P.V., Bailey, D., Forgie, S.E., Dingle, T.C., Krajden, M.

Interpreting Diagnostic Tests for SARS-CoV-2

John Bayhi — Thu, 07 May 2020 16:00:45 +0000

Date Added:

May 7, 2020

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 6, 2020

Pages:

[Epub ahead of print]

URL:

Interpreting Diagnostic Tests for SARS-CoV-2

Type:

Clinical Decision Aids

Format:

Article

DOI (1):

10.1001/jama.2020.8259

Keywords

COVID-19

diagnostic tests

SARS-CoV-2

2019 novel coronavirus

2019-nCOV

RT-PCR

ELISA

PMID (1):

32374370

Potentially useful information about when and how to use COVID-19 tests most effectively. James W. Mold, MD, MPH

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Author/s:

Sethuraman, N, Jeremiah, SS, Ryo, A

Benralizumab for the Prevention of COPD Exacerbations

John Bayhi — Thu, 12 Sep 2019 13:39:58 +0000

Date Added:

September 12, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

September 12, 2019

Issue:

Volume:

381

Pages:

1023-1034

URL:

Benralizumab for the Prevention of COPD Exacerbations

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1056/NEJMoa1905248

Keywords

benralizumab

chronic obstructive pulmonary disease

copd

PMID (1):

31112385

MeSH

benralizumab

eosinophils

pulmonary disease, chronic obstructive

interleukin-5 Receptor alpha subunit

Antibodies

Monoclonal

Humanized

Benralizumab (Fasenra) apparently does not reduce COPD exacerbations so probably no reason to try to remember its name. James W. Mold, MD, MPH

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BACKGROUND:

The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.

METHODS:

In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.

RESULTS:

In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.

CONCLUSIONS:

Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Author/s:

Criner GJ, Celli, BR, Brightling CE, Agusti, A, Papi, A, Singh, D, Sin, DD, Vogelmeier, CD, Sciurba, FC, Bafadhel, M, Backer, V, Kato, M, Ramirez-Venegas, A, Wei, YF, Bjermer, L, Shih, VH, Jison, M, O'Quinn, S, Makulova, N, Newbold, P, Goldman, M, Martin, UJ