Longevity
Early aggressive Crohn's treatment cuts surgery risk at five years, trial finds
By Life and Health Today Staff, . Life and Health Today.
Starting newly diagnosed Crohn's disease patients on intensive immune-suppressing therapy from day one leads to far fewer surgeries and hospital admissions over five years than the conventional approach of beginning with milder treatments and escalating only if those fail. That is the finding of a five-year follow-up of the PROFILE trial, reported in The Lancet and discussed by Rick Lange, MD, president of Texas Tech Health El Paso, and Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, on the TTHealthWatch podcast from Texas Tech.
Crohn's disease is a chronic inflammatory condition of the digestive tract. The conventional treatment ladder, known as step-up therapy, typically starts with steroids and adds stronger drugs only when the disease does not respond. The alternative tested here, called top-down therapy, begins immediately with infliximab, a drug that blocks tumour necrosis factor, a protein that drives inflammation, combined with an immunomodulator, a drug that damps down the immune system more broadly.
The trial enrolled 386 adults aged 16 to 80 with newly diagnosed Crohn's disease across 40 hospitals in the United Kingdom. Participants were randomly assigned to top-down or step-up treatment for 48 weeks, after which they returned to whatever their local standard of care was. Researchers then tracked outcomes for up to five years beyond that 48-week period. According to MedPage Today's account of the podcast, 93 percent of participants had records available for that longer follow-up.
The difference in surgical outcomes was substantial. During the follow-up period, 28 Crohn's-related abdominal surgeries occurred in 26 patients in the step-up group. In the top-down group, there were six surgeries in six patients. Patients in the step-up group also reached surgery sooner and were admitted to hospital more often, with a shorter time to first admission than those treated with the top-down approach.
Critically, the authors reported no meaningful differences in serious side effects between the two groups, according to MedPage Today. That matters because, as Lange noted on the podcast, hesitancy to use aggressive immune suppression early has long rested on concern that it raises the risk of infection and malignancy. The trial did not find that concern borne out.
One finding that Lange highlighted is that the benefit of top-down therapy was not confined to patients already considered high-risk at diagnosis. More than 90 percent of those in the step-up group eventually required maintenance immunosuppression anyway, suggesting the escalation was largely inevitable. The trial found that every patient, regardless of initial risk classification, appeared to benefit from starting intensive treatment earlier.
What this trial does not establish is whether these results translate directly to healthcare systems outside the UK, where treatment infrastructure, drug access and follow-up protocols differ. The study also does not tell us whether top-down therapy changes the underlying biology of Crohn's disease or simply delays complications. The open question, as Lange framed it, is whether earlier and more aggressive treatment genuinely alters the long-term disease course or whether the benefit narrows further out than five years.
The same podcast also covered a separate study, published in JAMA, of a drug called loberamisal for stroke patients who do not qualify for clot-dissolving or clot-removing procedures. In a trial of just under 1,000 patients conducted in China, 70 percent of those who received the drug intravenously for 10 days after a stroke achieved the best functional outcome at 90 days, compared with 56 percent in the placebo group. That finding is specific to the Chinese healthcare context, where fewer acute stroke centres mean more patients fall outside the window for standard interventions, and it would require further study in other settings before its relevance to other populations could be judged.
For anyone with a Crohn's diagnosis or a family member newly diagnosed, the question of which treatment approach to pursue is one that belongs with a gastroenterologist who knows the individual's full history.
Source: https://www.medpagetoday.com/podcasts/healthwatch/123064