Antibodies

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.

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.

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. 

Not available.