Tocilizumab holds little potential for treatment of COVID 19 patients with pneumonia: JAMA

Written By :  Medha Baranwal
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2020-10-23 23:45 GMT   |   Update On 2020-10-24 09:03 GMT

Delhi: Three JAMA studies have shed light on the use of the immunosuppressive drug tocilizumab for COVID-19 patients with pneumonia. One of them suggested some promise while the other two found no benefit. The studies are published in the journal JAMA Internal Medicine.The first study by Shruti Gupta, Brigham and Women's Hospital, Boston, Massachusetts, and colleagues, involved 3,924...

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Delhi: Three JAMA studies have shed light on the use of the immunosuppressive drug tocilizumab for COVID-19 patients with pneumonia. One of them suggested some promise while the other two found no benefit. The studies are published in the journal JAMA Internal Medicine.

The first study by Shruti Gupta, Brigham and Women's Hospital, Boston, Massachusetts, and colleagues, involved 3,924 adult COVID-19 patients admitted to intensive care units (ICUs) at 68 hospitals in the United States from Mar 4 to May 10. 

Key findings of the study include:

  • Patients treated with tocilizumab were younger (median age, 58 vs 63 years) and had a higher prevalence of hypoxemia on ICU admission (47.3% vs 37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab.
  • After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups.
  • 39.3% patients died, including 28.9% treated with tocilizumab and 40.6% not treated with tocilizumab.
  • In the primary analysis, during a median follow-up of 27 days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71).
  • The estimated 30-day mortality was 27.5% in the tocilizumab-treated patients and 37.1% in the non-tocilizumab–treated patients.

"Among critically ill patients with COVID-19 The risk of in-hospital mortality was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include the early use of tocilizumab," wrote Gupta and colleagues.

The second study by Carlo Salvarani, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy, and colleagues, involved 123 adult COVID-19 patients hospitalized from Mar 31 and Jun 11 with respiratory failure, a fever of at least 38°C (100.4°F) for at least 2 days, and/or elevated levels of C-reactive protein, an indicator of inflammation. 

Key findings of the study include:

  • Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses.
  • 28.3% in the tocilizumab arm and 27.0% in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05).
  • Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively.
  • The trial was prematurely interrupted after an interim analysis for futility.

"In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care," wrote Salvarani and colleagues. 

In the third study by Olivier Hermine, Assistance Publique - Hôpitaux de Paris, France, and colleagues, analyzed data on 130 patients hospitalized with COVID-19 and moderate to severe pneumonia in nine teaching hospitals from Mar 31 to Apr 18. 

Key findings of the study include:

  • In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the usual care alone (UC) group with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold.
  • At day 14, 12% fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold.
  • The HR for MV or death was 0.58.
  • At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92).
  • Serious adverse events occurred in 32% patients in the TCZ group and 43% in the UC group.

"Tocilizumab may reduce the need for mechanical and noninvasive ventilation or death by day 14 but not mortality by day 28; further studies are necessary to confirm these preliminary results," wrote Hermine and colleagues. 

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Article Source : JAMA Internal Medicine

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