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Lupus - better treatment in the pipeline?

Published on 07 October 2013
Source: Arthritis Today
Steroids to treat kidney disease in lupus: are they a necessary evil or drugs to be avoided at all costs? Dr Liz Lightstone's new clinical trial aims to find an alternative. Jane Tadman reports.
Dr Lightstone with Kajal Patel-Shah
Steroids are controversial drugs. They can save lives but also cause a host of deeply unpleasant side-effects when taken over a long period. For many years, steroids were the mainstay in treating inflammatory forms of arthritis, until the medical profession realised that what were once hailed as wonder drugs were actually causing osteoporosis, high blood pressure, weight gain, thin skin and mood swings.

Although in the short-term they can save lives in serious life-threating autoimmune conditions such as lupus, and in particular lupus nephritis (lupus affecting the kidneys), the damage caused by long-term steroid use actually contributes to the higher-than-normal death rate seen in lupus patients.

For the past few years doctors have been wrestling with this dilemma of whether steroids are a necessary evil, and the emerging consensus seems to be that while they still have a place in the short term in getting inflammatory conditions under control before other drugs then kick in, they should be avoided in the long term whenever possible.

Kajal Patel-Shah had a first-hand, distressing experience of steroids. Kajal, now 29, developed severe lupus nephritis seven years ago. She was extremely ill and nearly died after her kidneys were found to be functioning at only 20%.

Employment advisor Kajal, from west London, was put on the immunosuppressive drug cyclophosphamide for three months immediately after her diagnosis, and also high-dose oral steroids – standard treatment at that time for severe lupus. She suffered a very bad reaction.

“I hated the steroids,” remembers Kajal. “They worked as a treatment but I hated what they did to me. I felt sick all the time, lost my appetite, my face swelled up, and my body shape changed.

“They also had a psychological impact: because of what they did to my body, I was very paranoid and became very, very aggressive. I would also go through different types of emotions which I couldn’t explain at the time but now know were a sign of depression.

“I only realised the reason for those feelings was down to the steroids when I stopped taking them after a couple of years and I started to think more clearly.

“The key factor of overcoming these feelings is to realise that this isn’t the real you and that it is important for you to control your lupus, not for the lupus to control you. It’s mentally made me stronger.”

Her then boyfriend, now husband, Bhavesh has equally vivid memories of the effects of the steroids.

“It was probably the most difficult time for us simply because I knew it wasn’t really her, having known her before she was on the medication,” he says.

“She was very, very angry quite a lot of the time. It made things very difficult for us. At the same time, I was very aware of what she was going through and the effect the drug was having on her. I had to bite my tongue and be patient, and eventually she came out on the other side.

“Once her body got used to the medication, she went back to normal.”

Kajal’s nephrologist at Hammersmith Hospital, Dr Liz Lightstone, slowly weaned Kajal off steroids and onto a drug called mycophenolate mofetil (MMF), which held her disease in check for six years. Apart from a couple of steroid injections at the beginning of the treatment she has had no oral steroids since and has been in remission, with her kidneys functioning about 80%. Kajal has experienced one flare-up in that time, which Dr Lightstone treated with a newer lupus drug, rituximab.

The current standard of care for lupus nephritis is a combination of high-dose steroids and drugs such as cyclophosphamide or MMF, but despite such potent therapy only about 10-20%of patients will achieve remission within six months.

Says Dr Lightstone: “A problem as significant as the failure of effectiveness is the toxicity of the treatments. Steroids were first reported as beneficial for the treatment of lupus nephritis 60 years ago, but their continued use has come at a heavy price. Overall, steroids contribute to at least 25% of the damage seen in patients with lupus. There are also dreadful cosmetic side-effects which lead to people stopping their medication, and impairing their quality of life. So we decided that our priority was to mimimise long-term steroid use in our patients with lupus, combined with our increasing use of rituximab.”

Dr Lightstone believes that this approach could lead to a fundamental change in the way that lupus nephritis is treated. Following a successful pilot study, she was recently awarded funding over five years by Arthritis Research UK to run an international, multi-centre trial of a new steroid-sparing drug regime called ‘Rituxilup,’ which combines rituximab and MMF, compared with MMF and oral steroids. The pilot study showed that Rituxilup was safe and effective without the need for long-term steroids, with 90% of patients achieving complete or partial remission.
Dr Liz Lightstone with patient Kajal Patel-Shah, who has lupus nephritis
Dr Lightstone describes the subsequent trial, which starts to recruit this autumn, as a ‘game-changer’ for people with lupus. “Stopping the use of oral steroids as the standard of care would be the most significant change in the treatment of lupus in the past 60 years,” she adds.

“If this trial demonstrates that a combination of rituximab and MMF is as good as MMF and oral steroids, and it’s safe, then without a doubt where rituximab is affordable it will become the treatment of choice for people with lupus nephritis.”

Lupus expert Professor Anisur Rahman, a rheumatologist at University College London, has welcomed this new approach and agrees that it could mark a ‘step-change’ in the treatment of lupus nephritis.

“Long-term use of oral steroids in lupus nephritis has been universally accepted, but if we could use a regimen that avoids them altogether, it could make a big difference to patients,” he says.

The trial needs to recruit 252 patients in total andthe hope is that most of these will be from the UK – although centres in continental Europe and the USA are also involved as there is such interest in the study.

The team will be recruiting patients aged 12-75. Children have been included as often have very severe lupus nephritis and suffer severe side-effects with steroids. At the moment 18 adult and four paediatric rheumatology and kidney units are signed up to participate, but they would welcome interest from other centres.

Patients will be randomised to receive either standard care with MMF and steroids or rituximab and MMF. They will all receive some intravenous steroids at the very start. All patients will be followed up for a minimum of two years, and some for up to four years.

Kajal Patel-Shah is delighted that her nephrologist is running the trial which could benefit other sufferers and lead to alternatives to steroids becoming available. She has recently swopped MMF for another drug thought to be safer in pregnancy, azathioprine, as she now planning to start a family.

“Dr Lightstone says if I have any flare-ups during pregnancy, I may have to be put back on steroids, which I don’t want, but there may be no alternative,” she grimaces.

It’s a happy story for Kajal, who is able to lead a near-normal life. If Dr Lightstone’s trial has a positive outcome, many more people with lupus nephritis will be able to avoid what Kajal went through, and will find an effective treatment – with far fewer side-effects.

• Read about our second clinical trial into lupus in the winter edition of Arthritis Today.

What is lupus?

• Lupus (systemic lupus erythematosus or SLE) is a severe disease of unknown cause. in which the immune system attacks various tissues in the body, including the joints and the kidneys (lupus nephritis).
• It affects mainly young women.
• Lupus nephritis, which can result in kidney failure and be life-threatening, can affect up to 60% of patients with lupus and is more common and severe in people of African and Asian descent. 

What are steroids?

Steroids (also known as corticosteroids) are drugs used to reduce inflammation. Prednisolone is the most commonly prescribed steroid tablet for people with inflammatory forms of arthritis such as rheumatoid arthritis, lupus and polymyalgia rheumatica.

The longer steroids are taken and the higher the dose, the more likely they are to cause side-effects. These include:

• weight gain
• mood swings
• thinning of the bones (osteoporosis) and skin
• bruising easily
• indigestion
• a round face.

Lupus: a special report

George Plumptre

Two years ago former Times gardening correspondent George Plumptre donated a kidney to his brother Francis, when lupus caused his kidneys to fail. Now chief executive of the National Gardens Scheme, which made Arthritis Research UK its guest charity in 2010–11, he tells how his donation transformed his brother’s life.

Steroids Pros and Cons

Professor Helen Foster

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?

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