Towards the end of June 2021, biopharmaceutical company AbbVie shared that Upadacitinib (RINVOQ) reached both its primary and all secondary endpoints in a Phase 3 maintenance study evaluating the therapy for patients with ulcerative colitis (UC). In the trial, researchers evaluated both 15mg or 30mg upadacitinib daily. Ultimately, the therapy showed significant efficacy over placebo and helped 42% of patients (15mg) and 52% of patients (30mg) reach clinical remission.
According to AbbVie, upadacitinib is:
a JAK1 selective inhibitor being investigated to treat rheumatoid arthritis, Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, axial SpA Giant Cell Arteritis and Takayasu Arteritis and Hidradenitis Suppurativa.
While it is not yet approved in patients with UC, it is approved for patients with rheumatoid arthritis (RA) in both the United States and Europe. Additionally, upadacitinib is approved in Europe for patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) whose conditions do not respond well to other therapies. The therapy works by inhibiting JAK1 or JAK1/3.
Altogether, upadacitinib has been shown to be relatively safe and well-tolerated. However, some serious or life-threatening adverse reactions have occurred. Common side effects include:
- Upper respiratory infections
Please speak to your doctor if you experience any of the following adverse reactions, as they can be serious:
- Tears in the stomach or intestines
- Signs or symptoms include changing bowel habits, an unexplained fever, or stomach/abdominal pain.
- Blood clots
- Signs or symptoms include shortness of breath, pain or tenderness in the affected area, swelling, or sudden unexplained chest pain.
- Any symptoms of an infection (fever, fatigue, muscle aches)
Phase 3 Study
Within this Phase 3 maintenance study, researchers evaluated the safety, efficacy, and tolerability of upadacitinib – compared to a placebo – in patients with moderate-to-severe UC. During the trial, researchers used two doses of upadacitinib: 15mg and 30mg. Altogether, the primary endpoint was clinical remission after 52 weeks, with secondary endpoints being endoscopic improvement, HEMI, and corticosteroid-free clinical remission after a 1 year period. Patients included those who achieved any sort of clinical response after an 8-week induction/study period of 45mg upadacitinib.
Through the trial, findings included:
- Patients receiving either upadacitinib dose achieved histologic-endoscopic mucosal improvement (HEMI) and remission at a much higher rate than patients receiving a placebo. As a result, the trial met all secondary endpoints.
- Altogether, the treatment was relatively safe and well-tolerated, with no new safety-related issues. Common side effects included worsening UC symptoms, rising blood creatine phosphokinase, and the common cold. Patients receiving a placebo had more adverse reactions and worse infections than those receiving upadacitinib.
- 3 patients receiving upadacitinib experienced some sort of malignancy, compared to only one in the placebo group. Additionally, patients receiving upadacitinib also experienced more deep vein thrombosis and pulmonary embolisms than those receiving a placebo. However, no patient died during the study.
Ulcerative Colitis (UC)
An estimated 700,000 Americans currently live with ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD) which causes irritation, sores, and ulcers in the large intestine. Altogether, UC is largely immune driven. The immune system mistakenly believes that food, gut bacteria, or cells are foreign invaders, so the immune system attacks and causes symptoms. Typically, UC affects either those between 15-30 or older than 60; those of Jewish heritage; or those with a family history of UC. Altogether, patients may experience “flares” or symptomatic periods. During these, symptoms include:
- Abdominal pain and cramping
- Bloody stool/diarrhea
- Anemia (low red blood cell count)
- Joint pain
- Appetite loss
- Canker sores
- Sudden urgency to use the bathroom
- Unintended weight loss
- Nausea and vomiting
- Fecal incontinence