Rheumatoid arthritis drug anakinra in small study to treat COVID-19
14 May 2020. Related: COVID-19: investigational drugs, COVID-19.
Simon Collins, HIV i-Base
A small observational study reported in Lancet Rheumatology used the rheumatoid arthritis drug anakinra, a recombinant interleukin-1 receptor antagonist, for the treatment of COVID-19. [1]
The study was conducted in Milan in 29 patients hospitalised with COVID-19 (median age 62, many with comorbidities) who received daily high-dose intravenous infusions of anakinra at 10 mg/kg bodyweight for 21 days in addition to standard of care standard care (non-invasive ventilation (CPAP), hydroxychloroquine, and lopinavir/r). Results were compared to a non-randomised control group of 16 people who only received standard of care.
Respiratory improvements and reduced signs of cytokine activity including reduced C-reactive protein was reported in 72% (21/29) of patients. Survival was 90% (26 out of 29). Five of 29 patients (17%) needed mechanical ventilation.
This compared to persistent or recurrent increases in C-reactive protein in most of the control group. Respiratory function improved for half of the patients (8 patients, 50%), and 56% (nine of 16) survived. One patient received mechanical ventilation (6%).
The authors commented that anakinra has a stronger safety record compared with other cytokine-blocking agents and a shorter half-life, making it suitable for critically ill patients, but that their findings needed to be tested in larger randomised studies.
The study is also part of the prospective 1000-person COVID-19 Biobank study looking for predictors of response and outcomes to COVID-19. [2]
comment
A second study, reported in Lancet Rheumatology, included 52 adults hospitalised with COVID-19 from 26 March to 6 April 2020, who were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days). Results were compared to 44 historical controls with similar baseline characteristics. [3]
The study reported lower rates of ICU admission (for invasive mechanical ventilation) or death with anakinra: 13 (25%) vs 32 (73%); hazard ratio: 0.22 (95%CI 0.11 to 0.41), p<0·0001. This remained significant in multivariate analysis; HR: 0.22 (95%CI: 0.10 to 0.49), p=0·0002. Increases in liver aminotransferases were reported in seven (13%) vs four (9%) patients, respectively.
Reference
- Cavalli G et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatology DOI: 10.1016/S2665-9913(20)30127-2. (7 May 2020).
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30127-2/fulltext - clinicaltrials.gov. COVID-19 Patients characterization, biobank, treatment response and outcome predictor (COVID-BioB).
https://clinicaltrials.gov/ct2/show/NCT04318366 - Huet T et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatology. DOI: 10.1016/S2665-9913(20)30164-8. (29 May 2020)
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30164-8/fulltext
This report was updated to included comments about the second study on 29 May 2020.