The advent of biologic therapy has transformed the outcomes of patients with Rheumatoid Arthritis
(RA), but has also highlighted important issues for their development. Early attempts at T-cell driven therapies
gave mixed results with difficulties extrapolating from non-human models to first in man trials. There is currently
one T-cell modulating therapy – abatacept – licenced for use in RA. Cytokine inhibition has proven to be more
fruitful with a number of anti-TNF and IL6 agents either licenced for use in RA or in development. The B-cell depleting
therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed for RA treatment.
Overall the biologics show good efficacy in RA and have been shown to retard progression of radiographic joint
damage. However, this benefit comes with a burden of increased infection risk and a financial cost significantly
higher than conventional disease modifying therapies. As a result current UK licencing holds the biologics in reserve
following failure of a conventional therapy and the presence of moderate to severely active disease.
The long term use of the biologics in RA has highlighted the risk of immunogenicity, with significant proportions of patients developing
anti-drug antibodies and losing therapeutic effect. The side effect profile and cost also raise the question around duration of therapy and
trials of drug tapering following disease remission are now taking place with several biologic agents. Our inability to stratify patients to
the most appropriate biologic drug (stratified or precision medicine) has also catalysed a large and critically important research agenda.
Beyond identifying new biologic targets, the development of biosimilar agents will likely drive the future shape of the RA biologics market
as lower cost alternatives are developed, thereby improving access to these therapies.