Rheumatoid Arthritis New Treatments
Treatments in rheumatoid arthritis (RA) are constantly developing and operate via a number of different mechanisms. The most commonly used are painkillers, biological agents and DMARDs, or disease-modifying anti-rheumatic drugs; the last two are discussed here.
Types of biologic
There are two main types of biologic therapy: anti-TNF and non-TNF agents. Anti-TNF drugs inhibit tumour necrosis factor alpha (TNFa), which controls production of the immune proteins IL-1 (interleukin 1) and IL-6 (interleukin 6), which stimulate enzymes that destroy bone and cartilage.
Anti-TNF biologics are antibodies, or proteins of the immune system which attack TNFa. They are monoclonal antibodies, meaning they are produced as clones from a single cell. Examples are adalimumab (Humira), certolizumab pegol (Cimzia) and infliximab (Remicade). Etanercept (Embrel) is also an anti-TNF drug but acts slightly differently. They are given if your disease activity score (DAS28) is greater than 5 on more than one occasion and you have already tried two DMARDs. Normally they are combined with methotrexate.
Cimzia is recommended as second or third-line for severe RA after other anti-TNFs have been tried. Anakinra (Kineret) is sometimes used in juvenile RA, but the evidence is not strong enough for it to be recommended in most countries for adults, unless you are already taking it.
Most biologics are given by injection
Non-TNF agents include abatacept (Orencia), which inhibits T cells, rituximab (Rituxan or MabThera) and toculizimab (RoActemra). Abatacept isn’t recommended for adults in the UK but can be useful in juvenile idiopathic arthritis. Rituximab (Mabthera) is an anti-B cell drug which causes the death of B cells, which can break down bone and cartilage. It is usually reserved for second- or third-line therapy. Toculizimab is usually given after DMARDs and anti-TNF drugs have been tried, particularly if you cannot have rituximab for medical reasons. It is usually combined with methotrexate.
Taking the drugs
This type of drugs is usually given by injection. A study has recently been launched in the UK looking at the effects of reducing the dose of biological agents, which could have a knock-on effect on costs and side effects. The patients have been placed into three groups: the first receive the standard dose, the second have their doses reduced by a third and the third have doses reduced by two-thirds for six months. This trial is called OPITTRA (Optimising Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis).
Reasons that you should not take this therapy
You may not be given certain biologics if your arthritis is stable or not active, or before you have tried the standard treatments. Many are not suitable for those who are pregnant or breastfeeding, or if you have an infection, as they can cause birth defects and compromise your immune system. If you’ve had TB, other recurrent infections such as chickenpox, multiple sclerosis or cancer in the past, these can also be re-activated with biologics. Finally, they may affect the lungs and heart and may not be given if you have lung fibrosis (thickening) or certain heart conditions.
Some of the common side effects of biologics are mentioned above. Others include nausea, vomiting, diarrhoea, weight gain, heartburn, fatigue, sinusitis, pins and needles and night sweats. More serious effects where you should tell a doctor include stomach pain, bleeding, abnormal bruising, skin peeling, visual problems or chest tightness. Biologics are also associated with an increased risk of skin cancer.
New DMARDs are also being developed. Recently the drug company Pfizer developed the drug tofacitinib (Xeljanz), a Janus Kinase inhibitor which acts on an immune system enzyme, for moderate to severe RA. At present, it has been approved in Japan, Russia and the US but not Europe, who felt it was not effective enough and had risks of serious adverse effects including gastrointestinal perforation and cancer. However, Pfizer is looking to appeal this since the drug does not require injection and therefore could be beneficial for patients.
Trends in RA management
In this video Dr Gary Owens MD of Gary Owens Associates talks about the 2012 American College of Rheumatology guidelines and recent changes in treatment: https://www.youtube.com/watch?v=2Kv3FFl7IuY
Treating ‘to target’
Recently there has been a focus on achieving certain levels of test results such as swollen joint count, C-reactive protein blood levels and disease activity scores in RA, in a similar way to blood sugar levels in diabetes or cholesterol in heart disease. This method has been shown to have better outcomes than a non-targeted method.
Drug therapies which are currently under development include newer-generation monoclonal antibodies such as ocrelizumab and ofatumumab, which both deplete B cells. Some smaller molecules which inhibit protein kinases (enzymes in the immune system such as Janus Kinase, p38 or Spleen Tyrosine Kinase), which could be given by mouth rather than injected, are also showing promise.
1. Tadman J. It’s all about the dose. Arthritis Research UK. Accessed 25 April 2013. http://www.arthritisresearchuk.org/arthritis-information/arthritis-today-magazine/150-autumn-2010/all-about-the-dose.aspx.
2. CG79: Rheumatoid arthritis: The management of rheumatoid arthritis in adults. National Institute for Health and Care Excellence. April 2009, UK.
3. Rituximab. Medline Plus Drug Information. Accessed 25 April 2012. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a607038.html
4. Golumimab. Arthritis Research UK. Accessed 25 April 2013. http://www.arthritisresearchuk.org/arthritis-information/drugs/golimumab.aspx
5. Buch M, Emery P. New therapies in the management of rheumatoid arthritis. Current Opinion in Rheumatology. 2011 May;23(3):245–251.
6. Scott D, et al. OPTTIRA: Optimising Treatment With Tumour Necrosis Factor Inhibitors In Rheumatoid Arthritis: Is Dose Tapering Practical In Good Responders? A “Proof Of Principle” And Exploratory Trial. Accessed 25 April 2013. http://www.kcl.ac.uk/medicine/research/divisions/diiid/centres/ctu/research/trials/opttira/index.aspx.
Written by Dr Anne Parfitt-Rogers, Medical Writer, UK