FDA Approves Rinvoq for Giant Cell Arteritis Save

Based on the results of the SELECT-GCA study, the US FDA has approved upadacitinib (Rinvoq or UPA) for the treatment of adults with giant cell arteritis (GCA), also known as temporal arteritis. This is the 9th FDA approved indication for upadacitinib in the U.S. for use in rheumatology, gastroenterology, and dermatology.

GCA affects elderly adults with a large vessel vasculitis; and isthe most common vasculitis affecting adults in Western countries.  Earlier this month, the EMA uropean Commission also approved upadacitinib for the Treatment of Adults with GCA throughout the EU.

The approvals are supported by results of the pivotal Phase 3 SELECT-GCA trial, which was recently published in the New England Journal of Medicine.  In this 52 week RCT the primary endpoint of sustained remission* (46.4% for UPA 15 mg  vs. 29% on placebo)  in combination with a 52-week steroid taper regimen; p=0.002). Other important secondary endpoints were also achieved including: a) reduction in disease flares (34.3% UPA 15 mg   vs 55.6% PBO); and b) lower cumulative steroid use by 52 weeks (median exposure of 1615 mg versus 2882 mg, respectively; p<0.001).

"Glucocorticoids remain a mainstay of treatment of GCA but lead to substantial drug-associated toxicities. Additionally, relapse remains common for patients with this disease," said Peter A. Merkel , M.D., MPH, chief of rheumatology at the University of Pennsylvania , Philadelphia , and SELECT-GCA trial investigator. "We now have a new option to treat GCA. The results of this clinical trial show that upadacitinib offers patients the chance to reach sustained remission."

The product label has changed to add GCA as an indication for the treatment of adults with giant cell arteritis. The PI notes that upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine. 

• Dose: recommended dosage  15 mg once daily in combination with a tapering course of corticosteroids. RINVOQ 15 mg once daily can be used as monotherapy following discontinuation of corticosteroids
• Warnings: the same boxed warning for all JAK inhibitors, applies with use in GCA. Specifically warnings regarding risk of:
  • Increased risk of serious bacterial, fungal, viral, and opportunistic infections
  • Higher rate of all-cause mortality (CV mortality)
  • Certain malignancies (eg, lymphomas and lung cancers)
  • MACE (cardiovascular death, myocardial infarction, and stroke) 
  • Thrombosis (arterial and venous thromboembolic events) 
• Adverse reactions (≥ 5%) reported in GCA studies included upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea.