Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum characterised by intermittent flares of active disease with diarrhoea, rectal bleeding and rectal urgency, alternating with periods of remission. Although it is a chronic relapsing-remitting disease for which there is no known cure, symptoms can be manged with appropriate treatment.

Patients are classified into those who have mild-to moderate active UC, which is defined as <4-6 bloody stools per day with systemic disturbance, while severe disease is classified as >6 stools per day. In patients with severe active UC hospitalisation is advised.

In a recent webcast, hosted by Ferring and presented by Prof Simon Travis, Consultant Gastroenterologist at Oxford University and the John Radcliffe Hospital in the UK, the management of mild-moderately active UC through guideline-driven clinical practice was discussed. The focus was on optimising conventional therapy to decrease rectal bleeding and stool frequency and improve mucosal healing to achieve clinical and endoscopic remission. Prof Travis stressed the importance of “getting the basics right” by treating with the optimal drug, the right dose, the optimal route of delivery and providing education about adherence before expensive biological drugs are considered.

He emphasised the recommendations of the ECCO guidelines for the initiation of treatment of mild- to moderate disease that favour the use of the 5-aminosalicyclic acid (5-ASA) compound, mesalazine (PENTASA®) orally or rectally or in combination with the addition of corticosteroids in patients who don’t respond to mesalazine. In patients who don’t respond well to these treatments, who are intolerant or refractory to 5-ASA drugs and who experience side-effects with corticosteroids, the ECCO guidelines also recommend the use of budesonide MMX 9 mg.

Current recommendations for the initiation of treatment in patients with mild- to moderate disease include:

  • ·         PENTASA® enemas 1g daily, or
  • ·         Oral (4g) and rectal (1g) PENTASA® daily, or
  • ·         Other oral and rectal 5-ASA drugs, or
  • ·         Oral prednisolone and rectal 5-ASA
  • ·         Budesonide MMX 9m/d, or
  • ·         Start with prednisolone and 5-ASA with a plan to start early azathioprine

Prof Travis stressed the importance of the drug’s delivery system to ensure that it reaches the inflamed mucosa in the colon to resolve symptoms and induce and maintain remission.

“The problem with using ASA-5 drugs with pH-dependent release systems is that less than 10% of these drugs get to the distal colon in active disease and only a third when the colon is normal. You can overcome that with PENTASA® which is a time-dependent slow-releasing medicine that effectively delivers a high concentration of the drug to the colon compared to pH-dependent and azo-bond preparations,” Prof Travis said.

He referred to a meta-analysis that included three studies on PENTASA® that showed that mesalazine was significantly more effective than placebo in reducing Ulcerative Colitis Disease Activity Index (UCDAI) scores. In the PODIUM study once-daily, PENTASA® 4g was compared to a twice-daily regimen with PENTASA® to assess efficacy in terms remission maintenance and mucosal healing in patients with left-sided disease.

“It found that once-daily treatment with 4g was significantly better compared to 2g twice daily in achieving the study’s primary endpoint of clinical and endoscopic remission at eight weeks which was defined as no bleeding, normal stool frequency and mucosal healing,” Prof Travis noted.

The study also showed that both clinical and endoscopy rates were significantly higher with once-daily (4g) Pentasa in maintaining remission over a 12-month period (69%) compared to the twice-daily dose (60%), while the mucosal healing scores of the once-daily study participants was 84.4% compared to 78.8% in the twice-daily population.

He recommended the continuing use of mesalazine as maintenance therapy, citing the findings of two meta-analyses that confirmed the benefit of these drugs in reducing the risk of colorectal cancer in the long term.

Prof Travis noted that although treatment is effective in treating ulcerative colitis, it is an ongoing disease that requires strict adherence to therapy to prevent the recurrence of symptoms.

Managing refractory disease

Concluding his presentation, Prof Travis, advised on the management of refractory mild- to moderate disease. For these patients, he recommended that clinicians review the diagnosis and retake the history. Consideration should be given to the possibility of other conditions such as inflammatory bowel disease with mucosal prolapse, longstanding proctitis, infections, or the use of medications that could cause colitis. In patients with refractory disease, therapy should be optimised, using the optimal drug, the right dose, the optimal route of treatment and ensuring adherence through education, Prof Travis stressed.

References:

Live webcast: Management of mild-moderately active ulcerative colitis: Guideline-driven clinical practice today. 16 August 2019. https://webstreamlive.com/ferring/sg/160819/main.htm

Superior remission rates for once daily use of Pentasa® (mesalazine) in ulcerative colitis. https://www.ferring.com/en/media/press-releases/superiorplusremissionplusrates/

Bokemeyer B, et al. Mesalazine in left-sided ulcerative colitis: efficacy analyses from the PODIUM trial on maintenance of remission and mucosal healing. J Crohns Colitis. 2012 May;6(4):476-82.