Steroids in Rheumatoid Arthritis

(These are also known as corticosteroids or, more correctly, glucocorticoids).

What are steroids?

Steroids are naturally occurring chemicals that help to make the body work, and are also used as medicines. There are many different types of steroid, for example there are those used by weightlifters and body builders (anabolic steroids), but usually when we talk about treatment for arthritis we mean the glucocorticoids. Sometimes doctors also use the word corticosteroids. The glucocorticoids produced by the body are called cortisone and hydrocortisone and they help to control metabolism (the chemical reactions in the body's cells that convert fuel from food into energy). During the day, when you are active, there are more glucocorticoids produced. During the night, when you sleep, there are less glucocorticoids produced. Because of this, a new delayed-release tablet has been developed especially to deliver glucocorticoids in the middle of the night and  there is some evidence that this is more effective than controlling morning symptoms. If you have been a night shift worker for a long time, this day-night variation will swap over. If your body needs to work harder than usual, for example when you get an infection or other ilness, it produces extra glucocorticoids to help.

Do steroids affect inflammation?

One of the effects of glucocorticoids, especially if extra glucocorticoids are made by the body or taken as tablets, is to change the way the body's immune system works. The body's immune system usually protects you from infection and helps to repair cuts, bruises and other injuries. In some diseases, however, the immune system attacks part of the body. Rheumatoid arthritis is one of these diseases, and the immune system attacks the joints, causing inflammation inside them. It is this inflammation that causes the pain, swelling and stiffness in joints affected by rheumatoid arthritis. When there is a lot of inflammation in the body, we would expect extra glucocorticoids to be made. These would help to cut down the inflammation. One of the mysteries of rheumatoid arthritis is that, in spite of inflammation often occurring in many joints, the body does not produce very much extra glucocorticoid.

What is in steroid tablets?

Cortisone or hydrocortisone are used up by the body very quickly and so if these naturally occurring glucocorticoids were to be taken as tablets, their effects would wear off in just a few minutes. The synthetic glucocorticoid tablets used for prescriptions of prednisone and prednisolone last much longer (as do some injectable forms of glucocorticoid, such as depomedrone and triamcinolone). In the average person, all the cortisone and hydrocortisone produced in 24 hours would add up to the same amount of glucocorticoid as about 5 or 6mg of prednisone or prednisolone.

How do steroid tablets help rheumatoid arthritis?

The first and most obvious effect is to reduce inflammation. A low dose (for example 7.5 mg prednisone or prednisolone daily) will usually have a clear noticeable effect within a few days of starting treatment. Joint pain, stiffness and swelling will be less, particularly in the mornings when the body needs higher levels of glucocorticoid. A larger dose (for example 25 mg daily) will usually have a larger and quicker effect. Very large doses, given as one-off injections (called pulses), can often provide a quick improvement that can sometimes seem almost miraculous.

A second effect, more obvious to some patients than to others, is that glucocorticoids make you feel better in yourself. They provide a 'sense of well-being'. We do not know why this happens but in some people given large doses of glucocorticoid this can result in them becoming enthusiastically over-active and have difficulty sleeping at night.

A third effect is not obvious at all to patients. This is because glucocorticoids seem to work on another process in rheumatoid arthritis, different from inflammation. In most patients, the arthritis gradually damages the joints slowly, over the years (known as joint erosions). This damage can show up on x-rays of the joints (usually the hands and feet) but takes a long time to be visible from the outside. There is now very strong evidence that glucocorticoids (prednisone and prednisolone) are able to reduce this joint destruction.

If steroids are so good, why doesn't everyone take them?

The problem is firstly, that the benefits of glucocorticoid medication on symptoms often do not last and secondly that glucocorticoids can cause side effects.

The biggest improvements in symptoms, from injections, last the shortest time (days or weeks). Large regular doses of tablets can provide relief of pain and stiffness for many months, but the arthritis usually eventually breaks through. Low doses maintain a smaller but useful effect on inflammation for up to a year or so (and may continue to provide a 'sense of well being' for longer). In the end, however, if the rheumatoid arthritis remains active the symptoms of inflammation will gradually show themselves.

The other effect of glucocorticoids (protecting the joints from damage) has continued for as long as they have been tested. Indeed, the evidence now shows that patients treated early in their condition will continue to benefit from reduced joint damage many years later, even after the glucocorticoids have been stopped. However, this has not yet been properly tested in patients who have had their arthritis for many years. As the evidence is now so strong, the National Institute of Health and Clinical Excellence (NICE) recommends the use of low dose glucocorticoids to prevent joint destruction in newly diagnosed patients.

What side effects do they have?

It is the side effects of glucocorticoids that have given them a bad name in some peoples' eyes. There is no doubt that high doses of glucocorticoids over many months or years can (and usually do) cause serious side effects. We know this from the early enthusiasm of doctors to treat patients with high doses to control their symptoms when glucocorticoids were first discovered over 50 years ago. (In those days, the possible side effects were not known about until much later.) We also see these effects in patients with serious and life-threatening diseases (such as severe asthma, or even some rare but serious complications of rheumatoid arthritis) who need high doses of glucocorticoids just to stay alive. However, in lower doses the side effects take a long time to appear and are much less serious. Nevertheless, there needs to be a good reason for taking even low doses of glucocorticoids to balance against the side effects which might develop.

The biggest side effects of glucocorticoids usually only occur after high doses for long periods of time. They include diabetes, heart disease, high blood pressure and obesity. Other side effects can occur even on moderate or low doses. They include fragility of the skin (leading to bruising), thinning of the bones (called osteoporosis) and a tendency to put on weight and make the face more rounded in appearance. Patients who already have diabetes might find it harder to control. Also, once your body has got used to taking glucocorticoid tablets, it complains if the dose is reduced too quickly because it re-sets its internal glucocorticoid controls. Stopping suddenly can in theory be dangerous, and even stopping slowly can make you feel as if your arthritis is getting worse.In the UK (but no other country) patients taking glucocorticoids are often given a 'steroid alert card'. There are some side effects that might build up slowly over many years in some patients, even on a low dose of glucocorticoid. These are not easy to measure but probably mean that patients are slightly more likely to get heart problems and osteoporosis; although the latest evidence is that when treating rheumatoid arthritis these risks are very small, certainly very small when compared with, for example, the risk of getting lung cancer from smoking cigarettes.

Can the risks of steroids be reduced?

The risks depend on the total amount of glucocorticoid taken over the years (and the condition for which it is prescribed) so the best way to reduce the risks is to only take the lowest dose of glucocorticoid that is needed to do the job. There is now good evidence that the risk of osteoporosis can be reduced by taking bone protective treatment with the glucocorticoid. This anti-osteoporosis treatment will usually be prescribed if you are going to take more than 7.5 mg prednisolone for more than 6 months. Some doctors recommend anti-osteoporosis treatment for any long-term dose of glucocorticoids.

Are steroids safe to take during pregnancy/breastfeeding?

Glucocorticoids are taken during pregnancy and breastfeeding by many RA patients and are often considered safer than the other options of disease control during this period. Indeed, when pregnancy is being thought of we often stop the patient's routine anti-rheumatoid treatment and switch over to glucocorticoids instead. Your rheumatologist should be able to tell you if this is the most appropriate treatment for you to take during pregnancy/breastfeeding.

How do I know if I should be taking steroids?

The best treatment for an individual patient is best discussed between the patient and their doctor. A few people develop serious complications to their rheumatoid arthritis, which means that, in spite of the risks, it is still best for them to take even quite high doses of glucocorticoid. Patients who need rapid short-term control of symptoms might be given glucocorticoids by injection (which can be given into the muscle or directly into an affected joint) or as tablets for a few weeks or months. Patients who develop new rheumatoid arthritis are often offered prednisolone either at a low dose of 7.5 mg daily, or sometimes at a high dose (60mg daily) quickly reducing to the low dose over a few weeks, and then continue low dose treatment to control the joint destruction. The length of time that patients will remain on steroid treatment will vary between patients (and rheumatologists). Some patients may only be given low-dose oral steroids for the first few months following diagnosis, while others may stay on steroids for longer. There is evidence to suggest that patients can experience a continued reduction in the progression of the disease from steroids for 1 to 2 years, but this will not be appropriate for everyone, so the decision will be made on an individual basis. These patients can also get symptom improvement for a year or two as a kind of 'beneficial side effect'.

We should all try to avoid the trap of varying the dose of glucocorticoid to match the changes in the way arthritis inflammation causes symptoms. This usually leads to gradually increasing doses (as the effects of lower doses wear off) and then the risk of side effects becomes serious. As patients, you are well-placed to keep an eye on this and to look after your long-term future with the help of your healthcare team.

References available on request

Professor John Kirwan BSc MD FRCP, Consultant & Professor of Rheumatic Diseases at the University of Bristol

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