Rheumatoid arthritisInflammation of one or more joints of the body. is a common autoimmuneAny condition caused by the body’s immune response against its own tissues. condition resulting in progressiveContinuously increasing in extent or severity. joint damage. This article will be of help to anyone who would like more information about the latest treatments for rheumatoid arthritisA type of autoimmune arthritis featuring chronic inflammation of the small joints, especially in the hands and feet, and eventually leading to joint destruction and deformity.
Rheumatoid arthritis is a type of inflammatory arthritis that affects 1% of our population. In keeping with many autoimmune conditions it is more common amongst women. It is thought to arise through a complex interplay of geneticRelating to the genes, the basic units of genetic material. and environmental factors which leads to activation of the immune systemThe organs specialised to fight infection. and inflammationThe body’s response to injury. of the lining of the joint. This process results in redness, warmth, pain and swelling of the joints. The treatments we use in rheumatoid arthritis aim to suppress the inflammation, thus improving symptoms and also crucially preventing progressive damage to the joints. The inflammatory burden in rheumatoid disease is associated with osteoporosisA condition resulting in brittle bones due to loss of bony tissue. and increased cardiovascular risk, it is therefore important to screen for and address risk factors for these conditions also.
Rheumatoid arthritis can present in different ways but is classically a symmetrical arthritis involving joints on both sides of the body and primarily affecting the wrists and small joints of the hands and feet. Other joints which are commonly affected include the shoulders, knees and ankles. One third of patients present with quite an abrupt or acuteHas a sudden onset. onset of disease which is often associated with more generalised features such as fatigue, weight loss and low grade fevers. In others, the arthritis comes on gradually, or in older patients may present with pain and stiffness affecting the hip and shoulder girdle. Less commonly, patients may have involvement of a single joint or inflammatory disease outside the joints.
The early diagnosis of rheumatoid arthritis is important: research has shown that early initiation of treatment is more effective in the long-term and reduces the development of progressive joint damage. A diagnosis of rheumatoid arthritis requires review by a Rheumatologist who will take a history, perform a physical examination and request further bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. tests, x-rays and may consider referring you for an ultrasoundA diagnostic method in which very high frequency sound waves are passed into the body and the reflective echoes analysed to build a picture of the internal organs – or of the foetus in the uterus. or MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field. scan.
Particular blood tests of interest include the Erythrocyte Sedimentation Rate (ESRAn abbreviation for erythrocyte sedimentation rate, the speed with which red blood cells settle out of suspension in the blood. This indirectly measures inflammation in the body.), C Reactive Protein (CRPAn abbreviation for C-reactive protein, found in the blood. Raised levels of this protein suggest tissue damage or necrosis (death of cells).), Cyclic Citrullinated Peptide antibodiesSpecial proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. (CCP) and Rheumatoid Factor (RF). An elevated ESR or CRP is indicative of an inflammatory response which is seen in rheumatoid arthritis. RF is positive in 50% to 80% of rheumatoid arthritis patients but is also found in up to 5% of the population with no disease. It is therefore not a good test in isolation for diagnosing rheumatoid arthritis. CCP is a newer more specific test for rheumatoid arthritis. The presence of RF and CCP suggests the presence of more severe disease.
In early disease, x-ray radiographs of the hands and feet may only show soft tissueA group of cells with a similar structure and a specialised function. swelling or reduced bone mineralisation on either side of the involved joints. In established disease, erosions of the joint may be visible. Ultrasound and MRI scanning allow a more detailed assessment of the joints. Power Doppler Ultrasound has the ability to detect low velocity blood flow in small blood vessels which is often seen in inflammatory joint disease.
The treatment of rheumatoid arthritis has progressed dramatically over the last decade. Rheumatoid arthritis remains a spectrum of disease with some patients having very mild symptoms ranging to those with rapidly progressive joint destruction. Once joints have been damaged they do not heal very well, it is therefore important to suppress the inflammation early to limit any damage to the joints. If treatment is started early it is more likely to be effective. In choosing the appropriate treatment we need to balance the disease severity and likelihood of progressive joint damage against the possible side effects of therapy. There are four main groups of drugs used in the treatment of rheumatoid arthritis:
Non-Steroidal Anti-Inflammatory Drugs
Disease Modifying Anti-Rheumatic Drugs
NSAIDs such as naproxen can help to reduce pain and swelling in rheumatoid arthritis but are unable to control progressive joint destruction. If taken regularly they can cause ulcerationThe presence or formation of an ulcer - an abnormal break in epithelium, the outer layer of cells covering the open surfaces of the body. of the lining of the stomachthe organ or the body where food is stored and broken down and also carry a slightly increased risk of heart attackThe death of a section of heart muscle caused by an interruption in its blood supply. Also called a myocardial infarction. or strokeAny sudden neurological problem caused by a bleed or a clot in a blood vessel.. Although these drugs may be needed to control pain in the short term, it is preferable for them to be used on an occasional basis only.
Corticosteroids are used to achieve rapid control of inflammation whilst other medications take time to start working. They can be administered as an intra-muscular injection, directly into an inflamed joint or as tablets. Use of joint or muscleTissue made up of cells that can contract to bring about movement. injections is preferable as this approach minimises the long-term steroid exposure. However, sometimes patients may require oral prednisolone.
DMARDs control the underlying disease process in rheumatoid arthritis and slow or prevent progressive joint damage. They usually take a period of six weeks or more to start working and the dosage of these drugs may need to be increased gradually over time. This group of drugs includes oral DMARDs such as Hydroxychloroquine, Sulphasalazine, Methotrexate and Leflunomide. There is evidence that when these drugs are used in combination they can be more effective in controlling inflammation.
Methotrexate was one of the first drugs to be used in the treatment of rheumatoid arthritis in the 1980s and remains the ‘anchor drug’ both as a treatment alone and in combination with other therapies. Methotrexate is usually given as a once-weekly oral preparation, although in those patients who develop gastro-intestinalrelating to the intestines, the digestive tract between the stomach and the anus side effects it can be administered as a subcutaneous injection. Sometimes patients can feel nauseous or unwell with methotrexate, this usually settles as the body adapts to the medication and it is worth persevering with the therapy if the side effects are not too severe.
A new group of disease modifying drugs, referred to as the biologic therapies have had a significant impact on the management of rheumatoid arthritis over the last decade. These are injectable drugs that target a specific proteinCompounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. or molecule involved in the inflammatory process. They are only used if patients have failed treatment with oral DMARDs. The Biologic Drugs include the anti-TNFAn abbreviation for tumour necrosis factor, a protein that stimulates inflammation and causes cells to die. drugs (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab), Rituximab, Abatacept and Tocilizumab.
The anti-TNF drugs are the first line biologic agents used when conventional DMARDs fail. There are five different anti-TNF drugs available and whilst no ‘head-to-head’ studies have been undertaken they all appear equally efficacious with similar side effect profiles. The choice of which drug to use is largely governed by convenience of administration and the particular characteristics of the patient. Infliximab is given via an intravenousWithin a vein. infusion whilst etanercept, certolizumab pegol, adalimumab and golimumab are administered via subcutaneous injections. The long-term safety data for these drugs is good with no increase in the rate of solid malignancies although there is evidence of a slight increase in non-melanomaA malignant tumour arising from pigmented cells or melanocytes, most often in the skin skin cancers. An important potential side effect of these medications is the risk of infectionInvasion by organisms that may be harmful, for example bacteria or parasites.. Infection risk is greatest in the first six to twelve months of therapy. Where risk of infection arising through use of these drugs is a concern, a choice of an anti-TNF agent with a shorter half-life is preferable. There is an increased risk of tuberculosisAn infectious disease caused by the bacterium Mycobacterium Tuberculosis. arising during treatment with anti-TNF drugs. Screening patients for evidence of previous tuberculosis exposure and treating accordingly can reduce the risk of active tuberculosis. We routinely undertake a chest x-ray and interferonA substance that can inhibit viral growth.-gamma release assay (blood test) in these patients. We also screen patients for hepatitisInflammation to the liver with accompanying damage to liver cells. B, as there is a risk of fulminant hepatitis developing in the context of active hepatitis B infection. Anti-TNF drugs should not be used in patients with heart failureFailure of the heart to pump adequately. or a history of de-myelinating disease such as multiple sclerosisA progressive disease of the central nervous system..
If despite anti-TNF therapy there is persistent disease activity, an alternative anti-TNF drug can be trialled. However, studies suggest that it may be more effective to start treatment with Rituximab. Rituximab depletes B cells in the peripheral blood. It is administered by two intravenous infusions a fortnight apart and is usually repeated when symptoms return which can be from six months to three years after the initial treatment. Rituximab carries a similar risk of infection to the anti-TNF drugs. This is greatest in the three-month period after an infusion and may be linked to low immunoglobulin G levels, which are routinely checked prior to each infusion. There is no increased risk of tuberculosis reactivation, although screeningA way to identify people who may have a certain condition, among a group of people who may or may not seem to for hepatitis B infection is advised.
Alternative biologic agents for the treatment of rheumatoid arthritis include tocilizumab and abatacept. Tocilizumab blocks the IL-6 receptor and is administered intravenously once a month. Abatacept is also administered intravenously and blocks T cellA type of lymphocyte, a white blood cell that fights infection. co-stimulation. Tocilizumab and abatacept have a similar risk of infection to the anti-TNF drugs. Tocilizumab has been associated with bowelA common name for the large and/or small intestines.perforationThe formation of a hole in an organ or tissue. and should therefore be avoided if there is a history of diverticulitisInflammation of the diverticula in the intestine, particularly in the colon. Diverticula are small pouches that protrude from the walls of hollow organs such as the colon. or stomach ulcers. Abatacept should be used with caution in patients with chronic obstructive pulmonary diseaseEmphysema and bronchitis; often associated with smoking and air pollution. Abbreviated to COPD. in light of an increase in pulmonary complications in this population.
Due to the increased risk of infection with rheumatoid disease and use of biologic therapies, it is advisable to have the pneumovax and influenzaA viral infection affecting the respiratory system. vaccinations, ideally prior to starting treatment. However, the vaccine response on anti-TNF and even rituximab does appear to be sufficient and vaccination is therefore advisable if prior immunisation cannot be achieved. Live vaccines such as yellow fever are not recommended whilst using biologic drugs due to a theoretical risk of developing infection.
For the majority of patients the treatments used are long-term or life-long therapies. After a period of stability we may try to reduce DMARD or biologic therapy. During this time you will need to be monitored closely for reactivation of the disease. If the arthritis does flare it may not be possible to control it with the same dosages or medications previously employed. Research has shown that you are more likely to achieve drug free remissionThe lessening or disappearance of the symptoms or signs of a disease. in the future if treatment is started early.
The outlook for rheumatoid arthritis is good. A large amount of research has been conducted into rheumatoid arthritis and we now have a wide range of effective therapies. There are also new treatments on the horizon. It is important to be reviewed by your specialist regularly and to aim towards tight control of your disease.