Australian researchers have developed a biomarker-derived model for predicting which patients with Crohn’s disease will benefit from early biologic therapy.

The Crohn’s Immunomodulator CRP-Albumin (CICA) Index uses the readily available measures of an elevated CRP and low albumin to predict the likelihood of immunomodulator failure.

A retrospective study of 410 adults with luminal Crohns’ disease found 56% experienced immunomodulator failure – defined as a new stricture, abscess or fistula, need for surgery or treatment escalation to biologic therapy. The median time to treatment failure was 16 months.

“In the full multivariable model, independent predictors of treatment escalation to biologic therapy included maximum CRP ≥ 5 mg/L (HR 3.96), minimum albumin < 35 g/L (HR 1.90), complex disease behaviour (HR 1.82), ileal location (HR 1.59), age < 40 years (HR 1.38) and baseline steroid requirement (HR 1.35),” the study said.

However in developing a predictive model for the risk of failing immunomodulator treatment, the researchers found a formulae utilizing maximum CRP and minimum albumin was the best discriminator.

CICA outperformed other models such as CRP-albumin ratio and faecal calprotectin.

Essentially, patients in the low risk group (CICA < –1.06) had a 2% probability of failing immunomodulators by one year, and 18% probability by 3 years.

“It would therefore be reasonable to initiate immunomodulator monotherapy in this group, especially if additional risk factors such as latent infection preclude early biologic therapy,” the study said.

“Patients in the high-risk group [CICA > –0.20] had a 47% probability of failing immunomodulators at 12 months, and by 36 months the majority had failed. Hence, based on these data, such patients should ideally be considered for early or upfront biologic therapy.”

“The disease course for patients in the moderate risk category [CICA –1.06 to –0.20] is less clear and individualised decision making should be undertaken, with consideration of additional risk factors such as complex disease behaviour, ileal disease location and concomitant perianal involvement.”

“Understanding which patients are likely to benefit from earlier biologic introduction is beneficial to patients, clinicians and society alike, by potentially reducing disease progression and uncontrolled disease activity, as well as saving costs for the healthcare system.”

Senior investigator on the study Dr Abhinav Vasudevan, from Eastern Health, told the limbic that PBS restrictions mean Australian patients have to try an immunomodulator before a biologic.

“The model shows there are a group of people that will likely not benefit from this approach and would be better off going straight to a biologic.”

He said in some countries like the US, people have the choice of starting on a biologic.

“In our system, it would be more that you have a low threshold to move them up to a biologic; even if it’s not upfront, but early biologic therapy.”

This was consistent with a proactive approach to disease control.

“The modern approach would be if someone is not resolving on current medication, proactively move them towards the more effective therapies.”

He said STRIDE guidelines recommend an objective assessment such as endoscopy or faecal calprotectin every 3-6 months to guide therapy.

Meanwhile, the CICA Index required prospective validation and should be incorporated or compared to “…faecal markers, as well as potentially imaging, endoscopic and/or histologic findings to enhance discriminative performance,” the study said.