Sarilumab

Introduction to Sarilumab

Sarilumab is a human monoclonal antibody that functions as an interleukin-6 (IL-6) receptor antagonist. It was developed by Regeneron Pharmaceuticals and Sanofi and received FDA approval in 2017. Sarilumab is primarily used in the treatment of moderate to severe rheumatoid arthritis (RA) in adults who have not responded adequately to or are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs).

Mechanism of Action

Sarilumab works by specifically binding to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), inhibiting IL-6-mediated signaling. IL-6 is a pro-inflammatory cytokine implicated in various inflammatory processes, including T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. By blocking IL-6 signaling, sarilumab reduces inflammation and other disease activities associated with rheumatoid arthritis.

Indications

Sarilumab is FDA-approved for:

  • Treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more DMARDs.

Off-label uses being investigated include:

  • Treatment of severe COVID-19 in hospitalized adults with elevated inflammatory markers
  • Management of other inflammatory conditions such as giant cell arteritis and polymyalgia rheumatica

Administration

Sarilumab is administered as a subcutaneous injection. The recommended dosage for adult RA patients is:

  • 200 mg once every two weeks
  • Dosage can be reduced to 150 mg once every two weeks for management of neutropenia, thrombocytopenia, or elevated liver enzymes

It can be used as monotherapy or in combination with methotrexate or other conventional DMARDs. The drug is supplied in single-dose pre-filled syringes or pre-filled pens.

Efficacy and Safety

Efficacy:

  • Clinical trials have shown significant improvement in RA symptoms, physical function, and radiographic progression compared to placebo.
  • Sarilumab has demonstrated efficacy in patients who had an inadequate response to TNF inhibitors.

Safety:

  • Common adverse effects include neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.
  • Serious infections, including tuberculosis, have been reported.
  • Sarilumab may mask signs of acute inflammation, potentially delaying diagnosis of infections.
  • Regular monitoring of neutrophils, platelets, and liver enzymes is recommended.

Pediatric Use

As of 2024, sarilumab is not FDA-approved for use in pediatric patients. However, research is ongoing:

  • A Phase 2 study evaluating sarilumab in polyarticular-course juvenile idiopathic arthritis (pcJIA) in patients aged 2-17 years is underway.
  • Case reports have described off-label use in severe pediatric inflammatory conditions, but more research is needed to establish safety and efficacy in children.

Pediatricians should be aware of ongoing trials and potential future indications in pediatric rheumatology.

Special Considerations

- Infections: Serious and sometimes fatal infections have been reported. Patients should be screened for latent tuberculosis before starting sarilumab.
- Vaccinations: Live and live-attenuated vaccines should not be given concurrently with sarilumab.
- Laboratory Abnormalities: Monitor neutrophils, platelets, and liver enzymes before and during treatment.
- Pregnancy: Limited data available; may cross the placenta in the third trimester. Use during pregnancy only if potential benefit justifies potential risk to the fetus.
- Drug Interactions: Sarilumab may affect the metabolism of CYP450 substrate drugs. Dosage adjustments may be necessary for medications such as warfarin or oral contraceptives.



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