Canakinumab hits mark in COVID-19-related pneumonia

The interleukin (IL)-1β antibody canakinumab has demonstrated a promising efficacy signal in patients with COVID-19-related pneumonia, reducing the need for invasive mechanical ventilation and improving clinical status, according to a study.

“Blockade of the cytokine storm with [the drug] prevents clinical deterioration of patients with COVID-19 pneumonia, thereby favouring earlier hospital discharge and better prognosis,” the investigators said.

“To date, the use of other immunomodulatory agents such as tocilizumab and anakinra for the treatment of the cytokine storm related to COVID-19 has highlighted the potential importance of modulating this pathway in preventing worsening of disease,” they added. [Eur J Intern Med 2020;76:43-49; Lancet Rheumatol 2020;2:e325-e331; Microorganisms 2020;8:695]

The current analysis included 48 patients (79.17 percent male) with moderate COVID-19-related pneumonia treated with hydroxychloroquine, lopinavir/ritonavir or remdesivir, alone or in combination before entering the study. Of these, 33 patients received canakinumab 150 mg (administered subcutaneously on days 1 and 7) and heparin, while 15 were given high-dose heparin (10,000 IU) only.

Median age was similar in the two groups, 70 and 69 years, respectively. The patients presented the classical symptoms of COVID-19, including fever, cough, dyspnoea, and fatigue, and more than half of the population had cardiovascular comorbidities.

At baseline, among patients in the canakinumab group, 30.4 percent were on continuous positive airway pressure (CPAP), 45.4 percent were on supplemental oxygen, and 24.2 percent had a noninvasive ventilation (NIV) mask. The corresponding proportions of patients in the control group were 46.7 percent, 40 percent, and 13.3 percent.

By day 21, more than half of the patients in the canakinumab group were discharged from the hospital, while none of those in the control group were. This follows that the duration of hospitalization was shorter among those who received the IL-1β antibody (14 vs 26 days; p<0.001). [Int J Infect Dis 2020;doi:10.1016/j.ijid.2020.12.073]

Canakinumab exposure was associated with meaningful clinical improvement in ventilation regimens (p<0.001), the investigators said. “At 10 days after [its] last administration, we observed no clinical need for NIV, a reduction in the use of CPAP, [and] an improvement [in] use of supplemental oxygen; 21.2 percent [of the patients] restored breathing with ambient air.”

Moreover, patients treated with the drug achieved a significant increase in the ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction (PaO2:FiO2; p<0.001) and reduction in lung damage (p=0.01), along with considerable declines in immune/inflammation markers (C-reactive protein [CRP], IL-6, and ferritin) that were not seen in the control group. These data, according to the investigators, support the role of canakinumab in modulating the immune response/cytokine storm.

The IL-1β antibody was relatively safe, with patients experiencing only mild side effects such as injection site reactions, nausea, and headache. Heparin was also well tolerated and did not induce any serious adverse events. Survival at 60 days was higher with canakinumab plus heparin than with heparin alone (90.0 percent vs 73.3 percent).

“It is likely that canakinumab is more efficacious before the patient’s condition progresses from mild to severe (eg, increase of lung opacity, increased IL-6, CRP, and hypoxaemia), as early treatment may effectively control the deterioration of symptoms and complications related to the massive cytokine storm observed in patients with severe forms of COVID-19,” the investigators pointed out.

“However, the long-term safety of IL-1 inhibition remains to be investigated. Specifically, canakinumab produces sustained IL-1 suppression, and therefore vigilance is necessary to monitor for adverse events,” they added.

A randomized phase III clinical trial of intravenous canakinumab in hospitalized patients with COVID-19-induced pneumonia is ongoing, although the trial evaluates the efficacy of a higher dose (administered intravenously and by body weight).