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Recent developments in Crohn's disease have helped determine when to intensify therapy, provided new treatment options, and suggested better strategies for patients who lose treatment response.

Top-Down Treatment Beat Step-Up Approach

Early and intensive "top-down" therapy outperformed conventional "step-up" therapy for patients with newly diagnosed Crohn's disease, and clinical trial researchers said it should become the standard for most patients.

Among the 386 patients randomized in the PROFILE trial, sustained steroid- and surgery-free remission at 48 weeks was significantly more common in the group assigned to top-down therapy (immunosuppression with anti-TNF plus an immunomodulator), as compared with those assigned to an accelerated step-up approach with conventional treatment and steroids (79% vs 15%, P<0.0001).

There were fewer adverse events, including disease flares, in the top-down group (168 vs 315), as well as fewer serious adverse events (15 vs 42) and fewer complications requiring surgery (one vs 10), the researchers reported in The Lancet Gastroenterology & Hepatology.

Given that most newly-diagnosed patients fit the trial's inclusion criteria -- active symptoms, raised C-reactive protein or calprotectin of 200 μg/g or more, plus active inflammation on ileo-colonoscopy -- "the case appears clear-cut for implementation of top-down treatment as the standard of care for most patients is as soon as possible after diagnosis," the study authors concluded.

Biosimilar Approved for Stelara

The FDA approved a biosimilar version of the biologic ustekinumab (Stelara), but this new option may not be available until 2025.

The biosimilar, manufactured by Amgen, carries the brand name Wezlana and can be swapped interchangeably with Stelara, the FDA said. Indications for both drugs in adults are the same, including the treatment of moderate to severe Crohn's disease.

Both drugs are also approved for children ages 6 and older who have plaque psoriasis or psoriatic arthritis. Neither product has yet been okayed for pediatric bowel disorders. The labels for both drugs will contain all the same cautions and warnings, such as heightened infection risk.

An agreement between Amgen and Stelara's manufacturer, however, may keep Wezlana off pharmacy shelves until next year. Johnson & Johnson sued Amgen for patent infringement. The companies settled out of court. Full terms of the settlement , but Amgen said they will allow the company to sell its biosimilar of Stelara "no later than January 1st, 2025."

Promising Data on Dose Escalation of CT-P13

Escalating the dose of CT-P13, an infliximab (Remicade) biosimilar, in patients with IBD who lost response after infliximab induction improved clinical response and remission, according to data presented at the Crohn's & Colitis Congress.

Dose escalation of IV infliximab is an option for patients who lose response after induction therapy, but there is limited data for CT-P13 subcutaneous dose escalation in IBD patients, the researchers noted.

They conducted a post-hoc analysis of LIBERTY-UC and LIBERTY-CD, two parallel-designed randomized controlled trials that evaluated maintenance therapy with CT-P13 in patients with ulcerative colitis and Crohn's disease. Participants randomly received either subcutaneous CT-P13 120 mg or placebo as maintenance therapy starting at week 10 after induction and then dosed every 2 weeks. At week 22, participants who initially responded but lost response could escalate the CT-P13 dose to 240 mg.

Of the 231 trial participants with Crohn's disease, 16.9% escalated the CT-P13 dose. Their clinical response rate was 61.5%, and the clinical remission rate was 53.8%. Furthermore, 28.2% of Crohn's patients had endoscopic responses, 12.8% had endoscopic remission, and 31.8% achieved corticosteroid-free remission. There were no new safety concerns.

Skyrizi Outdid Stelara in Previously Treated Crohn's

Adults with Crohn's disease who failed tumor necrosis factor (TNF) inhibitor therapy had better responses to risankizumab (Skyrizi) compared with ustekinumab, according to clinical trial data presented at the European Crohn's and Colitis Organization Congress.

The open-label SEQUENCE trial enrolled 527 adult Crohn's patients with an inadequate response to at least one previous anti-TNF agent. One group received 600 mg of IV risankizumab at weeks 0, 4, and 8, followed by 360 mg of subcutaneous risankizumab every 8 weeks through week 48. The other group received baseline IV ustekinumab according to their weight and then 90 mg of subcutaneous ustekinumab every 8 weeks.

At 24 weeks, clinical remission based on Crohn's Disease Activity Index score occurred in 59.6% of patients who received risankizumab versus 42.6% of those who received ustekinumab (P=0.0001). The clinical remission rates at 48 weeks were similar. Clinical response rates for patients on risankizumab were significantly better at week 24 (69.8% vs 54.3%, P<0.001) and week 48 (67.5% vs 46.8%, P<0.0001).

Risankizumab, an interleukin (IL)-23 p19 inhibitor, gained FDA approval for the treatment of adults with moderately to severely active Crohn's disease in June 2022. Ustekinumab, an IL-12/23 p40 inhibitor, was approved for the same indication in 2016.

Anti-TNF Prevented Perianal Fistulas in Kids

Early anti-TNF therapy was associated with significantly lower risk of perianal fistulizing complications (PFCs) in children and teens with Crohn's disease, according to a post-hoc analysis of an observational study reported at the Crohn's & Colitis Congress.

Researchers analyzed data from 447 patients under the age of 18 who had been prospectively enrolled in the from 2008-2012. The patients were divided into three treatment groups: those receiving no immunosuppressive drugs; those taking immunomodulators, such as thiopurines or methotrexate, but no anti-TNF therapy; and those taking TNF inhibitors with or without immunomodulators or other medications.

Compared with the immunomodulator recipients, those on anti-TNF treatment had a 78% risk reduction for PFCs (OR 0.22, P=0.035). Compared with patients who received no immunomodulating treatment, the risk reduction was 83% (OR 0.17, P=0.0041).

Approximately 30% of children develop PFCs within 6 years of their Crohn's diagnosis. These complications are difficult to treat and commonly recur, the researchers noted. Prevention would save the cost of treatment and improve children's quality of life, they added.

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