In their new scientific publication, Professor Jon Rhodes and colleagues report that hydroxychloroquine in combination with two antibiotics, ciprofloxacin and doxycycline, induces a long-lasting remission in some people with Crohn’s Disease.
The malaria medicine hydroxychloroquine has had its fair share of news coverage recently because of its proposed use as a treatment for coronavirus. But long before the controversy of hydroxychloroquine and coronavirus, we funded Professor Rhodes’ project investigating this medicine as a treatment for Crohn’s Disease.
But how might this malaria treatment help people with Crohn’s? It’s believed that the inflammation in Crohn’s might, at least in part, be due to an altered immune response to bacteria found in the gut. Although antibiotics can be used to try to keep the gut bacteria under control, they don’t always work because the bacteria ‘hide’ inside immune cells. Experiments in the lab show that hydroxychloroquine counteracts the normally acidic environment inside immune cells called macrophages – and bacteria such as E. coli need this acidic environment to survive and multiply.
There is some evidence that bacteria, particularly E. coli, may be part of the problem in Crohn’s Disease. In this trial a combination of antibiotics (ciprofloxacin and doxycycline) with the anti-malarial hydroxychloroquine, previously shown to help immune cells to kill E. coli, induced remission in a small proportion of patients with active Crohn’s. There is sufficient promise to justify a further larger trial but this treatment meanwhile should not be used outside of a therapeutic trial.
The "Antibiotics and Hydroxychloroquine in Crohn's" (APRiCCOT) Clinical Trial
The APRiCCOT trial was led by Professors Jon Rhodes and Chris Probert and their team based at the University of Liverpool. The team found that the combination of antibiotics and hydroxychloroquine induced remission at a rate that was similar to a standard “mild” steroid – budesonide. Some patients also maintained remission long-term after their treatment with antibiotics and hydroxychloroquine stopped.
As the number of patients in this trial were small, a larger scale study with more patients is needed to uncover whether this treatment really does result in long-lasting remission. Importantly, this research has taken the first steps towards a bigger trial by showing that this drug combination is safe for people with Crohn’s, despite some mild side effects that were reported (including sensitivity to sunlight and nausea).
Trials like this offer an exciting opportunity to improve treatment options quickly. If we can repurpose existing treatments, then the time and cost involved in new clinical trials can be bypassed.
There are some promising signs, but more work is needed to definitively prove that the antibiotic/hydroxychloroquine combination can help people with Crohn’s Disease in the long-term.