Most Read Articles
Elaine Soliven, 20 May 2020
Early treatment with a triple antiviral combination of lopinavir-ritonavir, ribavirin, and interferon beta-1b significantly shortens the duration of virus shedding and reduces symptoms in patients with mild-to-moderate COVID-19 compared with lopinavir-ritonavir only, according to a recent study.
Pearl Toh, 26 Sep 2019
The Singapore Health Sciences Authority (HSA) has recalled eight brands of ranitidine products containing trace amounts of the nitrosamine impurity NDMA*, which is a potential human carcinogen.
Roshini Claire Anthony, 27 May 2020

The use of a vaginal cleansing intervention prior to Caesarean delivery reduced the incidence of surgical site infections (SSIs), according to a study presented at ACOG 2020. However, the addition of intravenous (IV) azithromycin prophylaxis had no added impact on SSI rates. 

Jairia Dela Cruz, 27 Mar 2020
Use of antioxidants for treating male factor infertility appears to be of little benefit, improving neither semen parameters nor DNA integrity, according to the results of the Males, Antioxidants and Infertility (MOXI) trial.

Another rheuma drug steps up in the battle against COVID-19

Audrey Abella
12 May 2020
Use of the interleukin(IL)-1 inhibitor anakinra led to clinical improvements in patients with coronavirus disease (COVID)-19, acute respiratory distress syndrome (ARDS), and systemic inflammation who are under noninvasive ventilation outside the intensive care unit (ICU), an Italian retrospective study has shown.
 
“Effective treatments for this population are needed urgently … [Our findings show that] administration of high-dose IV anakinra dampened systemic inflammation and was associated with progressive improvement in respiratory function in [this patient subgroup] in a setting overwhelmed by the COVID-19 pandemic and with a shortage of ICU resources. This allowed us to postpone or avoid intubation in most patients,” said the researchers.
 
Fifty-two consecutive patients (median age 62 years, 83 percent male) were included. Of these, 29 received high-dose anakinra (5 mg/kg BID IV) while seven received low-dose anakinra (100 mg BID SC) on top of a standard oral regimen (hydroxychloroquine 200 mg BID and lopinavir 400 mg with ritonavir 100 mg BID). The remaining 16 patients received the standard regimen only. All patients received respiratory support via CPAP*. [Lancet Rheumatol 2020;doi.org/10.1016/ S2665-9913(20)30127-2]
 
Low-dose anakinra was discontinued at day 7 due to the lack of meaningful clinical or anti-inflammatory effects. As such, comparisons were between the high-dose anakinra and the standard treatment arms only.
 
At 21 days, more anakinra vs standard treatment recipients (n=21 vs 8) achieved reductions in serum C-reactive protein and progressive improvements in respiratory function.
 
This translated to 13 anakinra recipients being discharged, three patients not requiring supplemental oxygen, three receiving low-flow supplemental oxygen, and two no longer having ARDS and weaning from CPAP. Among those who improved in the standard treatment arm, seven were discharged while one remained hospitalized on low-flow supplemental oxygen, explained the researchers.
 
While there were more patients in the anakinra vs the standard treatment arm who remained mechanically ventilated (n=5 vs 1), there were fewer deaths with the former than the latter (n=3 vs 7).
 
Survival rate was higher with anakinra vs standard treatment (90 percent vs 56 percent; p=0.009).
 
Anakinra was generally well tolerated, except for seven patients who discontinued treatment due to adverse events after a median treatment duration of 9 days. The rates of bacteraemia were similar between the anakinra and standard treatment arms (n=4 and 2, respectively).
 
Considering the frailty and risk factors of participants, termination of anakinra was deemed practical. Nonetheless, doing so did not result in relapses or worsening. These findings support the safety profile and short half-life of anakinra, which allows prompt discontinuation. “[Therefore, it is] suitable for use in critically ill patients,” said the researchers.
 
Going off-label
The sense of urgency during this pandemic has compelled the rollout of agents for off-label or compassionate use on a global scale (eg, remdesivir, immune-modulating compounds, and convalescent plasma). [N Engl J Med 2020;doi:10.1056/NEJMoa2007016; Antiviral Res 2020;177:104762; JAMA 2020;doi:10.1001/jama.2020.4783] “Our study arose from a specific need: medical management of [this patient population] to prevent death or escalation of intensity of care,” explained the researchers.
 
“Anakinra was one of the immediately available anti-inflammatory therapeutic options at the time of the COVID-19 outbreak,” said the researchers. Moreover, it is approved by the US FDA** and EMA***. Thus, anakinra may be a safe and controllable off-label alternative to curb the detrimental inflammatory effects of COVID-19, they added.
 
However, caution is warranted in interpreting the findings due to the retrospective design, small sample size, and uncontrolled nature of the study, the researchers pointed out. “[V]alidation is absolutely required in a controlled setting.” Moreover, longer trials are warranted to evaluate long-term outcomes in treated patients.
 
“[Nonetheless,] together with pre-existing evidence of the efficacy and safety of anakinra in patients with hyperinflammatory syndromes, [our findings] suggest that [anakinra] deserves consideration and controlled testing for the treatment of COVID-19,” they said.
 
A randomized phase 2 trial of lower doses of IV anakinra in patients with COVID-19 but not ARDS is underway.
 
Why target IL-1 in COVID-19?
Studies have identified associations between inflammatory biomarkers and the development of ARDS and death. [JAMA Intern Med 2020;doi:10.1001/jamainternmed.2020.0994; Lancet 2020;395:497-506] “IL-1 inhibition has transformed the care of many autoinflammatory diseases,” commented Drs Kate Kernan and Scott Canna from the UPMC Children’s Hospital of Pittsburgh in Pittsburgh, Pennsylvania, US, in a separate editorial. [Lancet Rheumatol 2020;doi.org/10.1016/ S2665-9913(20)30129-6]
 
In view of the study limitations however, the findings should be interpreted as “exploratory”, noted Kernan and Canna. “Also, the study did not detect a between-group difference in progression to mechanical ventilation, which tempers enthusiasm for the findings.”
 
Nonetheless, considering the biological, pharmacokinetic, and safety profiles of anakinra, as well as supporting literature, the findings are promising and support prioritizing this approach when rolling out randomized trials in the future, the editorialists added.
 
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Pharmacist - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Elaine Soliven, 20 May 2020
Early treatment with a triple antiviral combination of lopinavir-ritonavir, ribavirin, and interferon beta-1b significantly shortens the duration of virus shedding and reduces symptoms in patients with mild-to-moderate COVID-19 compared with lopinavir-ritonavir only, according to a recent study.
Pearl Toh, 26 Sep 2019
The Singapore Health Sciences Authority (HSA) has recalled eight brands of ranitidine products containing trace amounts of the nitrosamine impurity NDMA*, which is a potential human carcinogen.
Roshini Claire Anthony, 27 May 2020

The use of a vaginal cleansing intervention prior to Caesarean delivery reduced the incidence of surgical site infections (SSIs), according to a study presented at ACOG 2020. However, the addition of intravenous (IV) azithromycin prophylaxis had no added impact on SSI rates. 

Jairia Dela Cruz, 27 Mar 2020
Use of antioxidants for treating male factor infertility appears to be of little benefit, improving neither semen parameters nor DNA integrity, according to the results of the Males, Antioxidants and Infertility (MOXI) trial.