The introduction to the UK market of the first JAK inhibitors

We have been waiting for the arrival of a new class of drug which has been in development for a number of years, called JAK inhibitors. Advances in chemical engineering have allowed the production of so called ‘small molecule’ drugs, chemicals which are highly specific for blocking molecules that have been identified within cells that cause chronic inflammation. The advantage of these ‘small-molecular targeted synthetic disease modifying drugs’ is that they can be taken by mouth as tablets, unlike biologic disease modifying drugs. NICE have passed the first of the JAK inhibitors ‘baricitinib’ for use in the NHS with the following stipulations:

Baricitinib, with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to or who cannot have other DMARDs, including at least 1 biological DMARD, only if:

  • disease is severe (a DAS28 of more than 5.1) and
  • they cannot have rituximab and
  • the company provides baricitinib with the discount agreed in the patient access scheme

Baricitinib can be used as monotherapy for people who cannot take methotrexate because it is contraindicated or because of intolerance, when the above criteria are met.

Here NRAS Chief Medical Advisor, Professor Peter Taylor explains about this new class of drug:

The biological (anti-TNF) therapies that came to market at the end of the nineties and those targeting other parts of the immune system, such as IL6, B Cell and T Cell blockers, introduced in the early 2000s, are all ‘large-molecule’ biologic therapies which work by blocking action on the outside of cells. Because they are very large molecules they cannot be taken orally and are injected subcutaneously (under the skin) or given by intravenous infusion (or 'drip'). The JAK inhibitors are new small-molecule therapies that work on the inside of cells to affect cell signalling. Two of these new drugs are coming to the UK market in 2017. Because they are small molecules, they can be taken by mouth and herald a new class of so-called 'targeted synthetic' disease modifying drugs or 'small molecules' because unlike biologic drugs that are made in living cells and comprise large numbers of atoms, the 'small molecules' are chemicals comprising just a relatively few atoms.

What does cell signalling mean? Cell signalling has to do with the way that cells communicate with one another. The tissues and organs of our bodies are comprised of different sorts of cells and the material they secrete around themselves. In order for the organs and the whole body to function as a coordinated and integrated whole, the cells need to communicate with each other. One family of molecules that communicate between cells in this way are known as ‘cytokines’. Cytokines are small proteins that take part in all biological processes involved in health such as growth and repair, movement of cells, manufacture of blood and the regulation of immune function that in health protects us. But cytokines are also involved in the regulation of inflammation. In diseases, such as rheumatoid arthritis, these inflammatory cytokines are over active and fail to 'switch off' immune responses. A very important group of new drugs that have shown very impressive efficacy with an acceptable safety profile are the Jak inhibitors. ‘Jak’ is an acronym for the scientific term for a particular category of signalling molecules within the cell (Janus kinases). Two such drugs have undergone very extensive clinical trials and have approval for use in some parts of the world. Two Jak inhibitors that are expected to become available in the UK in 2017 are tofacitinib (trade name Xeljanz) and baricitinib (trade name Olumiant). These are oral drugs. They have a similar magnitude of benefit to biologic anti-TNFs. There are other Jak inhibitors in clinical trials at an earlier stage of development.

For more information, see NRAS publication: ‘Medicines in RA’ www.nras.org.uk/publications