SAVE-MORE subgroup analysis further reinforces anakinra benefit in COVID-19

The benefit of anakinra treatment in patients hospitalized with COVID-19 is consistent regardless of age, sex, comorbidities, and suPAR* levels, according to subgroup analysis of the SAVE-MORE trial.

“Anakinra represents an important therapeutic tool in the management of COVID-19 being equally effective in all subgroups of patients,” the authors noted.

Participants in the multicentre (37 centres in Greece and Italy), prospective, double-blind trial were 606 patients with confirmed SARS-CoV-2, lower respiratory tract infection, and plasma suPAR ≥6 ng/mL who required hospitalization. They were randomized 1:2 to receive subcutaneous placebo (n=189) or anakinra (100 mg; n=405) QD for 10 days, in addition to standard of care.

Previous results of the trial showed a reduced odds of worse clinical outcome (based on the 11-point World Health Organization Clinical Progression Scale [WHO-CPS]) with anakinra compared with placebo at 28 days (median 3 vs 4 points; odds, 0.36, 95 percent confidence interval [CI], 0.26–0.50). [Nat Med 2021;27:1752-1760]

The present analysis demonstrated that at day 28, the lower odds of experiencing worse outcomes with anakinra vs placebo were consistent regardless of age (≥65 years; odds ratio [OR], 0.41, 95 percent CI, 0.25–0.66; <65 years: OR, 0.29, 95 percent CI, 0.19–0.45) or sex (male: OR, 0.32, 95 percent CI, 0.21–0.49; female: OR, 0.44, 95 percent CI, 0.27–0.72). [eClinicalMedicine 2023;56:101785]

Similarly, the benefit with anakinra over placebo at 28 days was noted regardless of Charlson’s comorbidity index (CCI) score (CCI ≥2; OR, 0.34, 95 percent CI, 0.22–0.50; CCI <2: OR, 0.38, 95 percent CI, 0.21–0.68) or suPAR levels (suPAR >9 ng/mL: OR, 0.35, 95 percent CI, 0.19–0.66: suPAR 6–9 ng/mL; OR, 0.35, 95 percent CI, 0.24–0.52). Time between symptom onset and anakinra/placebo initiation also did not affect the benefit of anakinra vs placebo with odds of worse outcomes of 0.47, 0.43, 0.27, and 0.21 for patients who initiated anakinra at 0–7, 8–9, 10–11, and >11 days since symptom onset.

Additionally, anakinra demonstrated a significant benefit with regard to the absolute decrease of WHO-CPS at day 14 from baseline among patients aged <65 years, men, patients with CCI ≥2 or suPAR 6–9 ng/mL, and those who initiated treatment at 0–7 days from symptom onset. A significant benefit with anakinra was also noted in the absolute decrease in SOFA** score at day 7 among patients aged ≥65 years, men, patients with CCI ≥2, suPAR 6–9, and suPAR >9 ng/mL, and those who initiated treatment at 0–7 days from symptom onset.

Exploratory analysis showed that the benefit of anakinra persisted over the long term with a reduced risk of worse outcomes compared with placebo at day 60 (OR, 0.40, 95 percent CI, 0.28–0.57) and day 90 (OR, 0.46, 95 percent CI, 0.32–0.67). At day 60, more patients in the anakinra than placebo group were fully recovered with no viral RNA detected (71.1 percent vs 49.7 percent), and death rate was lower in the former vs latter group (5.2 percent vs 9.5 percent). A similar outcome was noted at day 90 (fully recovered with no viral RNA detected: 77.8 percent vs 61.4 percent; deaths: 5.4 percent vs 10.1 percent).

Anakinra also significantly reduced multiple costs compared with placebo, including that of general ward and ICU stay, medication, and total hospitalization cost until 90 days.

“In our study, use of anakinra reduced the total cost of hospitalization by almost 40 percent. This is of particular importance in a current era of stringent budgetary pressure, with expenditures needing to be reallocated to ensure best cost-effective quality of care for all,” the authors said.

*suPAR: Soluble urokinase plasminogen activator receptor

**SOFA: Sequential organ failure assessment