MHRA approves Rinvoq for moderate to severe Crohn’s disease

13th February 2023

Upadacitinib (brand name Rinvoq) was previously been approved for ulcerative colitis and is now licensed in moderate to severe Crohn’s disease.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has now approved upadacitinib for use in patients with moderate to severely active Crohn’s disease and who have had either an inadequate response or were intolerant to, conventional therapy or a biological agent.

Crohn’s disease is a form of inflammatory bowel disease that affects any part of the gastrointestinal tract and which is thought to affect around 10 million people worldwide and has a major impact on health-related quality of life.

Patients with Crohn’s will often receive oral corticosteroids to manage a disease flare, although those with more severe disease receive biologics either with or without immunomodulators to induce and maintain remission.

Upadacitinib is a Janus kinase inhibitor and a Phase II trial, evaluating the efficacy of 3 mg, 6 mg, 12 mg 24 mg twice daily or 24 mg daily, concluded that the drug induced endoscopic remission in a significant proportion of patients in comparison to placebo.

The MHRA decision was based on the findings of three other clinical studies and are reported in the press release.

In the first, U-EXCEED, a significantly higher proportion of patients treated with upadacitinib 45 mg daily achieved clinical remission per SF/AP at week 12 compared to placebo (40% vs 14%, p<0.001) and an endoscopic response compared to placebo (35% vs 4%, p<0.001).

In the second trial, U-EXCEL, again more patients given a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission (51% vs 22%, p < 0.001) and endoscopic response (46% vs 13%, p < 0.001) compared to placebo.

In the third study, U-ENDURE which was a maintenance trial, patients who had responded to 12 weeks of upadacitinib 45 mg, were re-randomised to 15 mg, 30 mg or placebo and assessed at week 52.

The results showed that clinical remission occurred in 36 and 46% respectively (i.e., for 15 and 30 mg) compared to 14% for placebo (p < 0.001).

Similarly, endoscopic response occurred in 28 and 40% compared to 7% in the placebo group (p < 0.001).

Interestingly, a recently published real-world study of upadacitinib in patients with Crohn’s disease has shown that the drug induced subjective and objective responses in 25% and 42% of patients, respectively.

Updated information on the indications for rinvoq can be found in the summary of product characteristics.

Upadacitinib approval for ulcerative colitis given by MHRA

2nd August 2022

Upadacitinib approval has been given by the UK’s MHRA for the treatment of patients with moderate to severe active ulcerative colitis

Upadacitinib approval has been granted by the MHRA for use in patients who have moderate to severe active ulcerative colitis according to a press release from the manufacturer AbbVie.

Ulcerative colitis (UC) represents a chronic idiopathic inflammatory bowel disorder of the colon that causes continuous mucosal inflammation extending from the rectum to the more proximal colon with an estimated prevalence of 7.6-245 cases per 100,000 persons/year. In the UK alone, ulcerative colitis has been estimated to affect 1 in every 420 people, amounting to around 146,000 people.

Symptoms of UC will include abdominal pain, bloody diarrhoea, severe urgency for a bowel movement, weight loss and fatigue. Both the severity of symptoms and uncertainty surrounding flares give rise to a substantial burden and often disability among those living with the disease.

Treatment for UC includes amino-salicylic acid, oral steroids and immunosuppressive drugs such as azathioprine and 6-mercaptopurine. However, 20% to 40% of UC patients do not respond to conventional medications and various biologics that target specific immunological pathways have been studied as potential treatments.

In a 2014 network meta-analysis, the authors concluded that compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. In addition, data also supports the use of Janus kinase inhibitors in the management of UC, with a study of patients having moderately to severely active ulcerative colitis, finding that tofacitinib gave rise to a better clinical response and remission compared to those receiving placebo.

The AbbVie press release describes how the approval of upadacitinib, was based on the results from three phase 3 clinical trials.

Upadacitinib clinical efficacy

The clinical efficacy comes from two induction trials, U-ACHIEVE induction and U-ACCOMPLISH and a single maintenance study U-ACHIEVE maintenance which are detailed in a single publication.

Patients aged 16 -75 years and with moderately to severely active ulcerative colitis for at least 90 days, were randomly assigned 2:1 to oral upadacitinib 45 mg once daily or placebo for 8 weeks. Patients who achieved the primary outcome after 8 weeks, which was an adapted Mayo score ≥2 points and ≥30% from baseline, plus a decrease in rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1, were re-randomised 1:1:1 to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks for the maintenance phase of the study.

The results showed that significantly more patients achieved clinical remission with upadacitinib 45 mg, 26% and 34% in both the induction trials (p < 0.001 for both trials) compared to the placebo group (5% and 4% for the two trials).

In the second phase of the trial, clinical remission was achieved by significantly more patients (p<0·0001) receiving upadacitinib 15 mg (42%) and 30 mg (52%) compared to those receiving placebo (12%).

The press release quotes Professor James Lindsay, Consultant Gastroenterologist at the Royal London Hospital Barts Health NHS Trust, who said that “in clinical trials, upadacitinib showed its ability to rapidly control symptoms in eight weeks for many participants and sustained responses at one year. I believe these results could make a positive difference for many people with ulcerative colitis for whom previous treatment options have not worked.”