Biologics were the first targeted therapies for rheumatoid arthritis (RA), 
having in common high clinical efficacy. Being proteins, they are administered 
parenterally. The first oral targeted small molecules approved for RA are 
competitive inhibitors of the Janus kinase (JAK) enzyme family which mediate 
signalling for a cytokine subset important in RA pathogenesis. Areas covered: 
Several JAK inhibitors have been developed with differing selectivity for the 
four JAK enzymes with a view to generating oral, multi-cytokine inhibitors. Here 
we review the pharmacology and clinical trial data for efficacy and safety of 
filgotinib, an investigational selective JAK1 inhibitor. We contextualise the 
contemporary approach to RA management and substantial unmet needs that remain. 
Expert opinion: The selectivity of filgotinib for JAK1 may have theoretical 
advantages in terms of limiting toxicity. However, establishing whether this is 
so before larger numbers of patients are exposed in phase III and beyond in the 
real word setting, will be difficult. Filgotinib clinical trial data to date has 
been encouraging with rapid, sustained efficacy with promising safety and 
tolerability. We are likely to see an expanding choice of approved JAK 
inhibitors in the clinic but it may not be straightforward to distinguish safety 
and efficacy differences.