Steroids Pros and Cons

Published on 01 January 2010
Source: Arthritis Today

Nicky Talbot and 7 year old daughter Emelye, who has JIA

Steroids have gone from being feted to feared – and hated for their side-effects. Do they still have a place in the treatment of inflammatory arthritis?

When the anti-inflammatory effects of glucocorticoids were discovered by Philip Hench and his collaborators back in the 1940s they were hailed as wonder drugs, very much in the same way that anti-TNF therapy is acclaimed now.

They transformed the treatment of rheumatoid arthritis (RA) and other forms of inflammatory conditions, and Hench went on to be awarded the Nobel Prize for his groundbreaking research.

However, although steroids were hugely effective in suppressing the effects of inflammation, it became clear in the 1950s that they were also responsible for some very unpleasant side-effects such as osteoporosis, diabetes, high blood pressure, thinning skin, weight gain and mood swings. Nor did they work for everyone.

The tide of medical opinion turned against steroids. “A whole generation of rheumatologists were very reluctant to use them,” recalls rheumatologist and now director of the Arthritis Research UK epidemiology unit Professor Deborah Symmons. “As a trainee, I had to get permission to prescribe them.”

Professor Symmons and many other rheumatologists and medics in current practice believe that the pendulum has now swung, if not all the way, but back towards the middle ground, and that steroids have their place – primarily as a means of getting inflammation under control in early disease while other more-long term therapies are started, and in damping down severe flares.

“Steroids are very useful in reducing the symptoms of rheumatoid arthritis in patients with early disease; they are also important in creating trust and confidence in the patient,” says Dr Arthur Pratt, a specialist registrar at the Freeman Hospital in Newcastle and an Arthritis Research UK clinical research fellow.

"Our practice at the Freeman is to use them as a tool for inducing remission in early RA, for example in an intramuscular pulse, or an intra-articular injection, as steroids work much more quickly than methotrexate. They are also useful to provide short-term relief if a patient is between drugs or is switching to a different disease-modifying anti-rheumatic drug (DMARD).”

Deborah Symmons concurs. “Steroids buy time. They make it possible for people to go to their wedding, or to celebrate their Golden Wedding anniversary. They also have a place in reducing flares. What we try not to do these days is to use them in tablet form as maintenance therapy over a long period, because of the side-effects.”

Professor Symmons ran a recent Arthritis Research UK clinical trial of more than 200 patients with very early inflammatory arthritis which showed that three intramuscular steroid injections given at weekly intervals postponed the need for the prescription of a DMARD in one in five people, and actually prevented one in ten people from developing RA. Interestingly, there was also no evidence that giving people who developed RA three steroid injections at weekly intervals very early in the disease process came to any harm by having their treatments delayed by the course of injections.

In conditions other than RA, side-effects of long-term steroid use are seen as a necessary evil. In lupus, where there are fewer newer, effective drugs than in RA, the doses have to be higher to control the potentially life threatening disease, and in lupus patients whose kidneys and brain are affected, the dose can be up to 60mg daily or more.

“Nothing acts faster than a steroid, so if time is of the essence, you give it, and tomorrow you think about trying something else, and get the steroid dose down,” explains Professor Symmons. “Very sick people with lupus have high doses of steroids to save their lives – although this may lead to long term problems it is a matter of balancing the benefit over the risk.”

Although the use of long-term oral steroids may be less common than in past years, there can be exceptions. Dr Pratt says he would only use them in special circumstances, for example in an elderly woman with longstanding RA to whom he would not want to give an anti-TNF drug.

And rheumatologist and Arthritis Today’s resident doctor Philip Helliwell has used long-term low dose (7.5 – 10mg) steroids in combination with other DMARDs on working men with manual jobs and kept them in work without any side-effects.

He thinks the use of steroids in treating inflammatory arthritis is more widespread than some clinicians would have us believe.

“If you look at any rheumatology department a quarter to a third of their patients – people with RA, connective tissue conditions like lupus and polymyalgia rheumatica – will be on oral steroids. And they still have many benefits – when used correctly,” he says. “A lot of us use them covertly – 90 per cent of all RA patients are given steroid injections into the joint to quell their flares or before they are put on methotrexate. They are seen as old-fashioned, and the current teaching orthodoxy is not to put people on them anymore – but it still happens. Steroids are ubiquitous.”

One condition for which a long-term low maintenance dose of steroids is usually prescribed is polymyalgia rheumatica, or PMR, with a bisphosphonate (bone-building drug) administered to counter any osteoporotic side-effects. “Steroid tablets are very effective in PMR,” says Deborah Symmons. “Most people are on them for two to three years, and we try to taper the dose down to 7.5mg fairly quickly, and slowly wean them off. A small number of people find their condition comes back once the dose is reduced, and will need other drugs, such as methotrexate or azathioprine which reduce the need for high dose steroids.”

The consensus among medics then, is that steroids still have an important part to play. “In an ideal world we wouldn’t give them at all because of the side- effects, but for inducing remission, and as an adjunct to other treatment they have to be considered,” says Dr Pratt. “In 2009, steroids still do have a role.”

Steroids in childhood arthritis

It’s in the treatment of juvenile idiopathic arthritis (JIA), where the use of steroids has changed most dramatically over the past few years, believes one of the country’s leading academic paediatric rheumatologists, Professor Helen Foster.

“The use of steroids has changed; we can’t use anti-TNF from the start of the disease but those who are on methotrexate and have an increasing number of flares can go onto anti-TNF, which is very effective and therefore enables us to reduce the amounts of steroids. Long-term side-effects are what we try to avoid,” she says.”

"You’re much less likely these days to see a child with a steroid-induced ‘moon face’, and one of the other side-effects – stunted growth – is now much less common. We rarely have to give growth hormone treatments now.”

Helen FosterThe current best use of steroids is to bring immediate relief to a sick child who is in distress. “A child can be miserable and unwell and within 12 hours of administering a steroid you have a different child – the effect is very dramatic,” adds Helen Foster (pictured left).

“It’s particularly effective in the case of systemic JIA which starts with a rash and fever; an intramuscular steroid pulse brings relief that can last several weeks. Then we’d prescribe methotrexate and possibly a low dose oral steroid too.”

Steroid injections into the joint are also given to children with arthritis, and are considered to be safe and effective. The down side is that a general anaesthetic has to be administered to very young children first because the injections are very painful and sometimes have to be given in up to eight joints.

Dr Madeleine Rooney, a paediatric rhematologist in Belfast, is heading an Arthritis Research UK funded clinical trial which aims to reduce thin bones (osteopenia) in children with JIA, and also rheumatic diseases such as juvenile dermatomyositis, lupus and vasculitis, who are taking steroids for their condition, by prescribing bisphosphonates. She is hoping the ongoing UK-wide trial will lead to world-wide guidelines on how to prevent steroid-induced osteopenia.

Nicky Talbot, whose seven-year-old daughter Emelye was diagnosed with JIA at the age of ten months, and has only recently stopped taking oral steroids, says she has an extremely positive view of the drugs.

“They got her through those initial years when she was too young to take anything else, and luckily for Emelye she didn’t suffer any of the associated side-effects such as the moon face or weight gain,” says Mrs Talbot, from Bangor in Northern Ireland.

Emelye, who is now on methotrexate, has also had steroid injections into her many affected joints over the years, which helped her retain a relatively normal and active life. “She is great at understanding her disease, and she knows what has to be done is for her own good, even though it might not be very nice at the time,” added Mrs Talbot.

Because of their side-effects and the fact they don’t work in everyone, researchers are keen to find alternatives to steroids. Several Arthritis Research UK funded scientists are currently engaged in this activity, including a team at the Kennedy Institute in London, who are investigating the ways in which glucorticoids function at the cellular level.

Another researcher is Dr Stuart Cooper, senior lecturer and clinical endocrinologist at the University of Birmingham, who has shown that the level of steroids within the bone rather than in the blood is a critical factor regulating the effects of glucocorticoids, and that these levels are determined by a particular enzyme that converts inactive steroids to their active forms. His team is examining the impact of this enzyme in the formation of bone-forming and bone-resorbing cells, its effects on osteoporosis, and its role in the adverse effects of steroids.

His research is ongoing, but so far he has found that the same process that sensitises bone to steroids also sensitises the synovial tissue. This would limit the usefulness of steroids that are designed to bypass these mechanisms, as the reduced effect on bone would be offset by a reduction in their anti-inflammatory effect. Dr Cooper is also in the process of finding out why bones are so affected by steroids. The aim is to enable better prediction of side- effects in people given glucorticoids, and develop new drugs with reduced bone effects.

What arthritis patients say about steroids:

“Five years ago I wasn’t able to do anything! Then I started prednisolone and I noticed the effect within a day!”

“I live by virtue of it; would have died without it.”

“When you get it, you feel on top of the world.”

“I wasn’t at all happy about my buffalo hump or the fact that I looked like I had eaten a small family. Any ideas where my huge face should go?”

“I don’t notice any positive effect at all and I have joint inflammation all the time.”

“I frequently feel I have to defend myself for my use of glucocorticoid therapy.”