Biologics, biosimilars and JAK inhibitors

Biologic medicines are proteins made by living, genetically engineered cells, rather than chemicals assembled in a laboratory. Most are antibodies: versions of the proteins the immune system itself uses, engineered so that each one recognises and blocks a single chemical messenger or cell type involved in inflammation.

That precision is what separates biologics from conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and sulfasalazine, which quieten the immune system in a broader, less targeted way. Both families share the same aim: to switch off the inflammation driving conditions such as rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, not simply to mask pain. Our guide to DMARDs in rheumatology covers the conventional medicines; this one covers the targeted treatments.

Because biologics are proteins, they would be digested like food if swallowed, so they cannot be made as tablets. They are given by injection under the skin or by infusion into a vein. In UK practice they are usually considered when conventional DMARDs have not controlled the disease well enough or have not been tolerated, and they are often taken alongside a conventional DMARD rather than instead of one.

Different biologics block different signals, and three groups cover most of those used in rheumatology.

TNF blockers. TNF (tumour necrosis factor) is one of the main chemical messengers driving joint inflammation. Anti-TNF medicines such as adalimumab and etanercept intercept it before it can act. This is the oldest and most widely used group, in use since the late 1990s, effective across rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, and some anti-TNF drugs also treat linked problems such as uveitis.

Interleukin blockers. Interleukins are another family of messengers, and different ones matter in different conditions. Tocilizumab blocks interleukin-6, an important driver in rheumatoid arthritis, while secukinumab blocks interleukin-17, which is particularly involved in psoriatic arthritis and axial spondyloarthritis.

B-cell therapy. Rituximab works differently. Rather than intercepting a messenger, it temporarily removes B cells, the immune cells that make antibodies, including the ones that attack the joints in rheumatoid arthritis. It is given as an infusion in a hospital day unit, and the effect of a course lasts many months.

No one target is simply stronger than another, which is why a biologic that fails to help one person may work well for the next: if the first target was not the right one for that person's disease, another can be tried.

When a biologic is first developed, its maker holds a patent. Once that expires, other manufacturers can produce their own versions. A medicine made in living cells cannot be copied exactly, in the way a simple chemical such as paracetamol can, so these versions are called biosimilars: medicines shown to match the original so closely that there is no meaningful difference in how they work, how well they work or how safe they are. The UK regulator approves a biosimilar only after detailed comparison with the original, and adalimumab, for example, is now available as several biosimilar versions under different brand names.

Being moved from an original biologic to a biosimilar, or between biosimilars, is a normal and closely regulated part of UK practice, and studies of these switches have found that effectiveness and safety are maintained. If your medicine changes name, the treatment itself has not changed in any way that matters. Even so, mention anything new you notice to your team.

JAK inhibitors, such as tofacitinib, baricitinib and upadacitinib, are the newest of the targeted treatments. They are not biologics: they are small chemical molecules, which is why they can be taken as tablets, and they are classed as targeted synthetic DMARDs. They work inside immune cells, blocking enzymes called Janus kinases that pass inflammatory signals from the cell surface to its control centre, so one tablet can quieten several messengers at once.

Their practical appeal is easy to see: a tablet rather than an injection, and an effect that often comes on quickly, sometimes within a few weeks.

They also come with a safety consideration that deserves a calm, honest airing. A large study of one JAK inhibitor, carried out in people aged 50 or over who had existing risk factors for heart disease, found more heart attacks and strokes, blood clots and certain cancers than in comparable people taking an anti-TNF biologic. As a precaution, the UK medicines regulator, the MHRA, now advises that in people aged 65 or over, in current or past long-term smokers, and in those with risk factors for heart disease, blood clots or cancer, JAK inhibitors should be used only when no suitable alternative exists. That is not a ban, and for people outside these groups JAK inhibitors remain effective, widely used medicines. It simply means the choice is made individually, with your own risk profile weighed openly, and with other options usually considered first in the higher-risk groups.

All of these medicines quieten part of the immune system, so a set of checks comes first. Blood tests are taken, and everyone is screened for tuberculosis and hepatitis B, sometimes hepatitis C as well, usually with blood tests and occasionally a chest X-ray. The reason is that these infections can sit dormant in the body for decades, held in check by the immune system. A treatment that lowers those defences can allow them to stir, so they are looked for first and, if found, treated before the new medicine begins.

It is also the moment to bring vaccinations up to date, because live vaccines, such as MMR and yellow fever, are generally avoided once treatment has begun. Non-live vaccines, including the flu, COVID-19 and pneumonia vaccines, are safe and recommended. Shingles deserves a particular mention with JAK inhibitors, as it is more common on these medicines, and a non-live shingles vaccine is available for those eligible.

The infection risk itself deserves perspective. It is real, but modest. Most infections that occur on treatment are the ordinary coughs, colds, skin and urine infections everyone gets, and they usually respond to standard treatment; serious infections are uncommon. The practical skill is not avoiding life, but acting on infections promptly rather than waiting them out. Our guide to infections and arthritis medicines covers this in detail.

The decision itself is made with your specialist, weighing your diagnosis, what you have already tried, your other health conditions and your preferences, including how you feel about injections versus tablets.

For a self-injected biologic, the medicine usually comes as a pre-filled pen or syringe kept in the fridge, and a specialist nurse teaches you the technique before you take it on yourself. Medicines given by infusion, such as rituximab, are administered in a hospital day unit over a few hours with observation. A JAK inhibitor is simply a tablet.

Monitoring continues once treatment starts: regular blood tests, and specialist reviews to check the disease is actually being controlled. Biologics typically begin to help within a few weeks, with the full effect building over about three months, while JAK inhibitors often act sooner; a difficult patch while you wait can be bridged, as covered in our guide to managing flares. Where it is unclear whether ongoing symptoms reflect active inflammation or something else, point-of-care ultrasound at a review can show directly whether the joints are still inflamed, which helps decide whether a treatment is doing its job.

These are high-cost, specialist-only medicines, and the way they are prescribed, supplied and monitored differs between NHS and private care. Dr Borukhson advises on whether one of these medicines is appropriate and, where treatment is needed, discusses how prescribing and monitoring would be organised, including where NHS services fit in.

Do not stop the medicine on your own. Stopping without advice commonly lets the disease return, and some biologics work less well when restarted after a gap.

Contact your GP or rheumatology team the same day if you develop a fever or signs of infection while on any of these medicines, such as a productive cough, burning when passing urine, or a hot, spreading area of skin. Significant infections are treated promptly, and the arthritis medicine is often paused until they clear, on your team's advice, which is quite different from stopping it yourself.

Call 999 or go to A&E for possible sepsis: fever with confusion or drowsiness, fast breathing, a racing heart, or feeling dramatically and rapidly unwell. A hot, swollen joint with a fever needs same-day emergency assessment, never a routine appointment, because infection in the joint must be excluded.

Sudden chest pain or breathlessness is always a 999 call. If you take a JAK inhibitor, also seek urgent same-day advice for a painful, swollen or red calf, which can signal a clot.

If you have never had chickenpox and have close contact with chickenpox or shingles while on treatment, seek advice promptly rather than waiting to see what happens.

Targeted treatments have transformed rheumatology. Conditions that once meant steadily accumulating joint damage can now usually be brought under control, and most people on these medicines live and work normally. The counterpart of that effectiveness is oversight: the right medicine chosen for the right person, screening done properly before the first dose, monitoring kept up rather than allowed to drift, and sensible decisions when infections, operations or pregnancy plans intervene. None of this is difficult, but all of it needs owning by a team that knows you. If one of these medicines is being considered for you, or you already take one and have questions, a specialist review can walk through the options and the practicalities, so it is understood as well as taken.

What is the difference between a biologic and a conventional DMARD like methotrexate?

Both are disease-modifying medicines: they treat the disease process itself rather than just the pain. Conventional DMARDs such as methotrexate are chemical tablets that quieten the immune system broadly, while biologics are engineered proteins that block one specific signal, such as TNF or an interleukin. In UK practice conventional DMARDs usually come first, with biologics or JAK inhibitors added or substituted when they are not enough. Our guide to DMARDs in rheumatology covers the conventional medicines in more detail.

I am being switched to a biosimilar. Should I be worried?

No. A biosimilar is a closely matched version of an original biologic, made by another manufacturer once the patent has expired, and approved only after the regulator is satisfied there is no meaningful difference in effectiveness or safety. Switching to a biosimilar is a normal, closely regulated part of UK practice, and studies of these switches are reassuring. The name on the pen may change; the treatment stays the same. If anything does feel different after a switch, tell your team rather than stopping.

Are JAK inhibitors safe? I have read about heart and clot risks.

They are effective medicines that most people take without problems, and the concern deserves accurate framing rather than alarm. A large safety study in older patients with heart-disease risk factors found more cardiovascular events, clots and certain cancers with a JAK inhibitor than with an anti-TNF biologic. The UK regulator therefore advises that in people aged 65 or over, current or past long-term smokers, and those with risk factors for heart disease, clots or cancer, JAK inhibitors are used only when no suitable alternative exists. Outside those groups they remain a widely used option, and the right approach is an individual discussion of your own risk profile before starting.

Will I have to inject myself?

Only for some medicines, and you will be taught properly first. Most self-injected biologics come as pre-filled pens designed for home use, a specialist nurse shows you the technique, and most people find it far easier than they feared. A few biologics, such as rituximab, are given as an infusion in a hospital day unit instead. JAK inhibitors are tablets, so no injections are involved at all.

How soon will my treatment work, and can I stop once I feel well?

Biologics usually begin to help within a few weeks, with the full effect building over about three months; JAK inhibitors often act faster. Feeling well on treatment usually means the medicine is doing its job, not that you no longer need it. Do not stop without specialist advice: the disease commonly returns, and some biologics work less well when restarted after a gap. If you become unwell, contact your team, who can advise whether to pause. Our guide to infections and arthritis medicines covers what to do when you are ill.