High-Dose Upadacitinib Maintenance Therapy for Refractory Crohn's Disease: A Case Series and Review of the Literature.

Introduction: Crohn's disease (CD) is a chronic, relapsing-remitting disorder affecting the gastrointestinal tract that falls under the umbrella term of inflammatory bowel disease (IBD). Its etiology is unknown, but it is suggested that there is a strong genetic and environmental interaction, leading to its development. The mainstay of treatment for patients with moderate to severe CD is advanced therapy, such as biologics or small molecules. Despite the use of these medications, the disease may be unresponsive to these agents, leading to refractory disease. The use of novel therapies expanded the treatment options for patients with refractory CD or those who failed multiple biologics. Upadacitinib (UPA), a small molecule drug, belongs to a class of medications known as Janus kinase (JAK) inhibitors. UPA is known to be effective against CD with a dosage of either 15 or 30 mg. However, this dose deemed to be ineffective in the cases we reported. A higher maintenance dose of 45 mg was introduced and the patient's reported resolution of symptoms. It is important to note that larger studies are required to prove the efficacy of this treatment for CD. Case Presentations: This is a case-series of 3 patients with a history of refractory CD and prior exposure to at least 1 biologic agent, who achieved clinical remission and endoscopic healing on UPA maintenance therapy 45 mg orally once daily. Conclusion: This case series illustrates potential benefit and supports the rationale for larger controlled studies evaluating high-dose UPA maintenance therapy.