New SLE Guideline Aims to Improve Diagnosis, Reduce Steroids

Janis C. Kelly

October 17, 2017

A new guideline on systemic lupus erythematosus (SLE) was released by the British Society for Rheumatology (BSR). The society's Standards, Audit and Guidelines Working Group published the guideline online October 6 in Rheumatology.

SLE affects nearly 1 in 1000 people in the United Kingdom (one-third of whom develop lupus nephritis), and patients with SLE die 25 years earlier than average, the authors write. This guideline is the result of BSR's major effort to improve the situation and is the first comprehensive guidance for the management of SLE in adults.

"We hope that the guideline will improve diagnosis by emphasizing the need to have at least one serological abnormality as well as relevant clinical features, to indicate that there [are] likely to be autoantibodies and immune complex-mediated pathology that will improve with treatments and drugs recommended to manage lupus," lead author Caroline Gordon, MD, professor of rheumatology and consultant rheumatologist, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham College of Medicine, United Kingdom, told Medscape Medical News.

"The 2012 European and American guidelines were specifically dealing with lupus nephritis. Our main focus and literature review were on nonrenal lupus, but we did summarize and include the main recommendations from the European lupus nephritis guideline, which we quoted and referenced," Dr Gordon added.

"We specifically did not review renal management, as this had only just been published when we started our plans for this UK guideline. We support the conclusions of the European renal guideline (which several of the authors including myself contributed to)."

The BSR guideline includes sections on clinical and serological features that should trigger consideration of possible SLE, assessment of patients with SLE, monitoring of SLE, and management of mild, moderate, and severe SLE.

The overall treatment strategy is that the smallest effective dose of corticosteroids should be used. "We anticipate reducing reliance on corticosteroids by recommending hydroxychloroquine (HCQ) as an anchor drug for all patients with lupus unless contraindications or intolerance," Dr Gordon said.

"We also recommend use of immunosuppressants if dose or frequency of steroid therapy is not optimal; for example, maintenance prednisolone of <7.5mg/day or need to reduce/stop/avoid steroids due to adverse effects/comorbidities. This should improve control of disease activity and prevent flares and complications from the disease and corticosteroids," she added.

For mild SLE, the authors recommend prednisolone or methylprednisolone plus HCQ and/or methotrexate (MTX), and/or nonsteroidal anti-inflammatory drugs. The aim is for a maintenance dose of 7.5 mg or less of prednisolone, 200 mg/day of HCQ, and/or 10 mg/week of MTX. For moderate activity or flare, the guideline recommends prednisolone or methylprednisolone; azathioprine or MTX or mycophenolate mofetil or ciclosporin; and HCQ. For severe activity or flare (nonrenal), the guideline recommends prednisolone and/or methyl-prednisolone, and azathioprine or mycophenolate mofetil or cyclophosphamide or ciclosporin, and HCQ. For all three types of SLE, the goal is to taper and stop all drugs except HCQ for stable remission.

"The recommendations in the guidelines are substantially the same as the ways US doctors manage adult SLE," Bharat Kumar, MD, clinical assistant professor of internal medicine, University of Iowa Carver College of Medicine, Iowa City, told Medscape Medical News.

"It is good to have the compendium of resources and references that support the BSR recommendations. There are some differences between the guideline and common clinical practice in the [United States]. For example, the BSR guideline recommends [MTX] for moderate SLE. Typically, we don't use that regimen in the [United States]. We tend to favor azathioprine or mycophenolate mofetil. We would like to see more randomized trials of MTX in lupus." Dr Kumar was not involved in preparation of the BSR guideline.

"We want to ensure that patients are given appropriate immunosuppressants. And those in the reproductive age group who might become pregnant should receive appropriate advice about avoiding pregnancy/contraception if they are taking drugs that are contraindicated in pregnancy," Dr Gordon told Medscape Medical News.

"We hope that the guidelines will ensure that patients are appropriately monitored, particularly with screening for renal involvement and high blood pressure, as well as clinical features of lupus and adverse effects of drug therapies to ensure that they get timely therapy, reduce complications of the disease, and to improve short- and long-term outcomes," she explained.

"Patients that are doing well still need to be monitored as renal disease is silent and patients are at risk of disease recurrence when they reduce or stop therapy." Dr Gordon noted that an example of this is pop star Selena Gomez, who in September underwent a kidney transplant for lupus.

The guideline also includes advice on use of belimumab and rituximab. Dr Gordon said, "[P]atients with severe disease, particularly if unresponsive to or intolerant of conventional immunosuppressants, should be referred to or discussed with specialized centers experienced in managing lupus and be offered belimumab, rituximab or clinical trial participation if they meet the relevant criteria."

"It is good that the guideline mentions belimumab and rituximab. Right now we use rituximab in refractory SLE cases, but this has been based mainly on anecdotal evidence and has not shown clear benefit. Results from RCTs have been disappointing for rituximab in lupus, but that might be because patients with severe refractory lupus were not included," Dr Kumar told Medscape Medical News.

"Belimumab is sometimes used in cutaneous lupus. The guidelines add some subtlety and nuance to guidance on the use of these drugs in lupus," he said.

Dr Gordon and Dr Kumar agreed on the need for better evidence for the use of immunosuppressive and biologic drugs in lupus, as well as the need for new drugs.

As a way forward, Dr Kumar emphasized the need for good biomarkers for lupus activity. Laboratory markers and other clinical markers provide information about lupus activity but are not reliable for predicting lupus flares. He said there is also an urgent need for more data on different lupus subtypes and phenotypes, which may respond differently to treatment.

He said, "We also need more information about the basic immunology of lupus. We still don't understand why lupus develops, what the risk factors are beyond the epidemiological issues, or why some patients develop severe disease while others develop more limited lupus. This has a major impact on clinical trial design because we need this information to properly stratify patients and to develop inclusion and exclusion criteria. How can we tell if a treatment is beneficial or not when we don't have a comprehensive, validated definition of what lupus is?"

The American College of Rheumatology, the British Society for Rheumatology, and the European League Against Rheumatism are working on defining a disease that has many heterogeneous subsets. "These groups are doing the best they can to provide rational guidance on diagnosis and management of SLE based on the best available data, but there are some major holes in the data," Dr Kumar said.

Various study authors report consultancies, honoraria, research funding, or other support from pharmaceutical companies including GlaxoSmithKline/Human Genome Sciences, Roche, Union Chimique Belge, Eli Lilly, Aspreva/Vifor Pharma, Bristol-Myers Squibb, MedImmune, Merck Serono, Parexel, Astra-Zeneca, GlaxoSmithKline, MedImmune, Pfizer, Genzyme Sanofi, INOVA Diagnostics, Actelion INB, AbbVie, Roche/Genentech, Boehringer Ingelheim, Chemocentryx, Aurinia Pharmaceuticals, Celegene, XTLBio, Anthera, Baxalta, and Rigel. A complete list of disclosures is available on the journal's website. Dr Kumar reported no relevant financial relationships.

Rheumatology. Published online October 6, 2017. Full text

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