Dual biologic therapy may help patients with refractory Crohn’s disease avoid avoid disease progression and recurrent surgery, preliminary data suggest.

A North American study examined outcomes of trials of simultaneous biologic therapy in 22 patients whose disease was refractory to an average of four individual biologics. The vast majority of patients (91%) had experienced prior surgical resection.

Vedolizumab was paired with a TNF-antagonist in 13 trials of therapy (54%), or with ustekinumab in 8 trials (33%), while ustekinumab was combined with a TNF-antagonist in 3 trials (12.5%).

Prior to adding in the second biologic, most patients (79%) were also receiving an immunomodulator. A third of patients were receiving corticosteroids and a third were on antibiotics.

The study found endoscopic improvement ( >50% reduction in the Simplified Endoscopic Score-Crohn’s disease [SES-CD]) in 43% of the therapeutic trials and endoscopic remission in 26% of trials.

“Clinical response occurred in 50% of therapeutic trials, clinical remission was achieved in 41% and steroid-free clinical remission was achieved in 36%,” the study authors said.

“Presence of perianal fistulas declined from 50% at baseline to 33% post-treatment. Surgery was required after 33% (n = 8) of therapeutic trials and these were considered treatment failures.”

There was no significant difference in endoscopic response rates when comparing reasons for prior biologic failure.

At one-year follow-up, 38% of patients remained on dual biologic therapy.

Nonresponse or worsening of disease activity requiring surgery were the most common reasons for discontinuing dual biologic therapy. Adverse events were reported in only three trials.

The study authors concluded that dual biologic therapy was promising

“This is particularly evident when considering the limited available therapeutic options in this cohort of refractory Crohn’s disease patients,” they said in Alimentary Pharmacology and Therapeutics.

Commenting on the study, Associate Professor Graham Radford-Smith told the limbic the trials did appear to show dual biologic therapy was safe and effective.

“Most clinicians are aware of dual biologic therapy and some of them may have considered it but it is difficult because of cost and the way in which we access biologics. The majority of patients in Australia will access a biologic through the PBS due to the costs involved.”

“Attempting to start two biologics is not possible through the PBS and therefore one would have to lobby the company to provide the second biologic and I think general speaking that would be difficult.”

Associate Professor Radford-Smith, from the Royal Brisbane and Women’s Hospital and QIMR Berghofer, said the study also raised the issues of why patients become “refractory”.

“Now have they failed four biologics or have we failed them? We don’t necessarily interrogate what are the key factors that lead to refractoriness and they are not always purely disease-related,” he said.

“There is enormous heterogeneity in clinical practice and also in human behaviour that can generate a refractory case.”

He said the study was a reminder of the need to optimise every single agent.

“There are a number of different mechanisms by which you can try to maximise the value of a very expensive, potentially very valuable drug. If you’re not doing that you are wasting a drug and wasting an opportunity for the patient.”

“Firstly, if you are going to use a chimeric antibody like infliximab, then ideally you should absolutely be trying your best to ensure they are started with a concomitant immunomodulator at least for the first three months but probably the first 12 months.”

“In patient with a significant burden of disease, eg … they have an evolving stricture, do you really want to start the biologic in that patient or may it be best to have a conversation with them and their colorectal surgeon to de-bulk them in the same way we debulk cancer, remove that really inflamed diseased segment and then consider starting the biologic postoperatively?”

“These are examples of where you can really optimise patient care and reduce the risk of that patient evolving into a “refractory” case and failing a biologic.”