Higher anti-TNF drug levels could improve radiological outcomes in perianal fistulising Crohn’s disease patients, according to a study by Australian gastroenterologists.

A review of 193 Crohn’s perianal fistula patients on infliximab or adalimumab showed those with radiological healing or remission had higher median drug levels than patients with active disease.

At median 2.5 and 2.1 years of maintenance therapy, 47% and 45% of patients achieved radiological healing and 17% and 16%, radiological remission on infliximab and adalimumab respectively.

Patients experiencing radiological healing had 6.0 vs 3.9 µg/mL infliximab or 9.1 vs 6.2 µg/mL adalimumab (both, P < 0.05), while those in remission had 7.4 vs 3.9 µg/mL (P < 0.01) infliximab or 9.8 vs 6.2 µg/mL adalimumab (P = 0.07), according to a study led by Dr Michael De Gregorio from St Vincent’s Hospital, Melbourne.

Previous studies had linked anti-TNF levels to improved clinical healing and closure on physical examination though their impact on radiological outcomes was unclear, the authors wrote.

This study “is just really solidifying and fortifying data we already have about clinical outcomes and showing that it holds true for deeper remission or healing based on MRI”, Dr De Gregorio told the limbic.

This is important, because, “anecdotally, I think, we know radiological outcomes are a deeper form of remission, they’re more sensitive and sometimes you can see radiological activity even if clinically, everything looks ok.”

“The study didn’t evaluate it, but I would suspect that having radiological remission or deeper control of disease radiologically would be associated with better and longer term outcomes — so decreased risk of relapse etc. — although that’s speculation because that’s not what the study looked at,” he said.

Despite finding similar benefits with higher anti-TNF levels to those studies, the researchers produced different results regarding optimal cut-offs.

“The median trough levels associated with radiological healing [4.0 µg/mL] and remission [6.5 µg/mL] in our study were numerically lower than those previously reported in association with clinical healing and closure … with optimal infliximab cut-offs for clinical healing and closure of 10.1 μg/mL,” they noted.

The “counterintuitive” outcome may be partly explained by assay variability and selection bias, the study investigators said. Patients with refractory disease would typically receive escalated and/or more frequent doses of anti-TNF therapy, “skewing the average drug levels in patients with active perianal disease, with subsequent over-estimation of recommended targets”, they explained, noting that their study featured a relatively low proportion of patients on escalated doses.

Additionally, there was “marked variability in individual response at a given drug level, with a proportion of patients achieving radiological healing and remission with low drug levels and others displaying persistently active disease despite drug levels above optimal cut-offs”.

“Although we quoted the optimal drug levels from when we did our analyses, I think you can’t really take them by themselves,” Dr De Gregorio said.

“The takeaway is that you should use levels to guide [treatment], but they’ve got to be taken in the whole clinical context — so if you’ve got a patient that’s got active disease and they have low levels, then we know that higher levels will be focused with better outcomes. But be mindful that the optimal cut-offs that we calculated, the receiver operator characteristic curve is not great, so I wouldn’t be using those to say: ‘if you haven’t got this, you’re not going to heal’.”

Essentially, prescribers should not necessarily make treatment decisions based on drug levels alone, Dr De Gregorio explained.

Longer anti-TNF therapy duration was associated with a greater likelihood of radiological healing while increased disease duration, perianal fistula complexity and/or number impeded therapy response.

“This emphasises the reality that anti-TNF drugs are only one component of the optimal management for perianal fistulising disease,” the authors wrote.

Drainage during examination under anaesthetic within 12 months of perianal imaging helped reduce anatomically complex perianal fistulas and “further [supported] a multimodal approach, as per current guidelines”, they added.

The findings are published in Clinical Gastroenterology and Hepatology.