Rheum Drugs & IDSA Guidelines to Treat COVID-19 Save

The Infectious Diseases Society of America (IDSA) has a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists who have developed treatment guidelines and evidence based position statements since early 2020. They recently updated their recommendations, especially with regards to the treatment of severely ill, hospitalized COVID-19 infected patients and also about the appropriate use of anti-IL-6, JAKs and colchicine.

Therapies have evolved as the evidence has evolved from many trials in treating the coronavirus disease 2019 (COVID-19). These recommendations from the panel looks at prioritized questions and outcomes, performs asystematic review of the peer-reviewed and grey literature and uses the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations.

The new document updates the recommendations of May 31, 2022, wherein the IDSA guideline panel made 32 recommendations for the treatment and management of the following groups/populations: pre- and post-exposure prophylaxis, ambulatory with mild-to-moderate disease, hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines.

The following recommendations pertain to rheumatologic drugs:

Hydroxychloroquine

• Hydroxychloroquine/Chloroquine + Azithromycin
  • Recommendation 1: Among patients with COVID-19, the IDSA guideline panel recommends against hydroxychloroquine. (Strong recommendation, Moderate certainty of evidence) Remark: Chloroquine is considered to be class equivalent to hydroxychloroquine.
  • Recommendation 2: Among hospitalized patients with COVID-19, the IDSA guideline panel recommends against hydroxychloroquine plus azithromycin. (Strong recommendation, Low certainty of evidence)  Remark: Chloroquine is considered to be class equivalent to hydroxychloroquine.
• Hydroxychloroquine for Prophylaxis
  • Recommendation 3: In persons exposed to COVID-19, the IDSA guideline panel recommends against hydroxychloroquine. (Strong recommendation, Moderate certainty of evidence)

Glucocorticoids

• Recommendation 7: Among hospitalized critically ill patients* with COVID-19, the IDSA guideline panel recommends dexamethasone rather than no dexamethasone. (Strong recommendation, Moderate certainty of evidence)   Remark: If dexamethasone is unavailable, equivalent total daily doses of alternative glucocorticoids may be used. Dexamethasone 6 mg IV or PO for 10 days (or until discharge) or equivalent glucocorticoid dose may be substituted if dexamethasone is unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.
• Recommendation 8: Among hospitalized patients with severe**, but non-critical, COVID-19, the IDSA guideline panel suggests dexamethasone rather than no dexamethasone. (Conditional recommendation†, Moderate certainty of evidence)   Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge) or equivalent glucocorticoid dose may be substituted if dexamethasone is unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.  
• Recommendation 9: Among hospitalized patients with mild-to-moderate*** COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation††, Low certainty of evidence)

Interleukin-6 Inhibitors

• Recommendation 11: Among hospitalized adults with progressive severe* or critical** COVID-19 who have elevated markers of systemic inflammation, the IDSA guideline panel suggests tocilizumab in addition to standard of care (i.e., steroids) rather than standard of care alone. (Conditional recommendation†, Low certainty of evidence)Remarks: Patients, particularly those who respond to steroids alone, who put a high value on avoiding possible adverse events of tocilizumab and a low value on the uncertain mortality reduction, would reasonably decline tocilizumab. In the largest trial on the treatment of tocilizumab, criterion for systemic inflammation was defined as CRP ≥75 mg/L. 
• Recommendation 12: When tocilizumab is not available, for patients who would otherwise qualify for tocilizumab, the IDSA guideline panel suggests sarilumab in addition to standard of care (i.e., steroids) rather than standard of care alone. (Conditional recommendation†, Very low certainty of evidence)   Remark: Patients, particularly those who respond to steroids alone, who put a high value on avoiding possible adverse events of sarilumab and a low value on the uncertain mortality reduction, would reasonably decline sarilumab.

Pre-Exposure Prophylaxis    Neutralizing Antibodies for Pre- and Post-Exposure Prophylaxis

• Recommendation 20: In moderately or severely immunocompromised individuals at increased risk for inadequate immune response to COVID-19 vaccine or for persons for whom COVID-19 vaccine is not recommended due to a documented serious adverse reaction to the vaccine, the IDSA guideline panel suggests pre-exposure prophylaxis with tixagevimab/cilgavimab rather than no tixagevimab/cilgavimab, when predominant regional variants* are susceptible** to the agent (Conditional recommendation†, Low certainty of evidence)Remarks: Dosing for tixagevimab/cilgavimab is 300 mg of tixagevimab and 300 mg of cilgavimab administered as two separate consecutive intramuscular injections once.
• Recommendation 21: In persons exposed to COVID-19 who are at high risk of progression to severe COVID-19, the IDSA guideline panel suggests post-exposure casirivimab/imdevimab only when predominant regional variants* are susceptible** to the agent. (Conditional recommendation†, Low certainty of evidence)

Janus Kinase Inhibitors

• Recommendation 23: Among hospitalized adults with severe* COVID-19, the IDSA panel suggests baricitinib with corticosteroids rather than no baricitinib. (Conditional recommendation†, Moderate certainty of evidence)
  • Baricitinib 4 mg per day (or appropriate renal dosing) up to 14 days or until discharge from hospital.
  • Baricitinib appears to demonstrate the most benefit in those with severe COVID-19 on high-flow oxygen/non-invasive ventilation at baseline.
  • Limited additional data suggest a mortality reduction even among patients requiring mechanical ventilation.
• Recommendation 24: Among hospitalized patients with severe* COVID-19 who cannot receive a corticosteroid (which is standard of care) because of a contraindication, the IDSA guideline panel suggests use of baricitinib with remdesivir rather than remdesivir alone. (Conditional recommendation†, Low certainty of evidence)   
  • Baricitinib 4 mg daily dose for 14 days or until hospital discharge. The benefits of baricitinib plus remdesivir for persons on mechanical ventilation are uncertain.
• Recommendation 25: Among hospitalized adults with severe** COVID-19 but not on non-invasive or invasive mechanical ventilation, the IDSA panel suggests tofacitinib rather than no tofacitinib. (Conditional recommendation†, Low certainty of evidence)
  • Tofacitinib appears to demonstrate the most benefit in those with severe COVID-19 on supplemental or high-flow oxygen.
  • Patients treated with tofacitinib should be on at least prophylactic dose anticoagulant.
  • Patients who receive tofacitinib should not receive tocilizumab or other IL-6 inhibitor for treatment of COVID-19.
  • The STOP-COVID Trial did not include immunocompromised patients.

Colchicine

• Recommendation 31: In hospitalized patients with COVID-19, the IDSA panel recommends against colchicine for treatment of COVID-19. (Strong recommendation, Moderate certainty of evidence)
• Recommendation 32: In ambulatory persons with COVID-19, the IDSA panel suggests against colchicine for treatment of COVID-19. (Conditional recommendation††, Moderate certainty of evidence)