Review of Current Lupus Treatments Highlights Both Potentials and Risks

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by Magdalena Kegel |

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Clinical management of systemic lupus erythematosus (SLE) is challenging, and aims mainly to slow or prevent organ damage, particularly kidney injury. A review, publisThed in the journal ImmunoTargets and Therapy, shows that while immunosuppressive and biological agents form the basis of disease control in lupus, clinicians need to be aware of their potential impact on comorbidities.

The review, Current and emerging treatment options in the management of lupus, was authored by Natasha Jordan and David D’Cruz from the Cambridge University Hospitals and Guy’s and St Thomas’ Hospital NHS Foundation Trusts, respectively, in the U.K.

Because lupus is a complex disease, each clinical manifestation needs a unique treatment approach. Lupus treatment is divided into induction and maintenance phases. No guidelines are available for long-term maintenance treatment beyond three years, but a general consensus exists that corticosteroids should be tapered as soon as possible.

Cardiovascular disease and osteoporosis are among the disease’s most common comorbidities, and risk is heightened in patients on corticosteroids for prolonged periods. Over-reliance on such treatment is a major problem, contributing to organ damage. The study’s authors recommend that clinicians be vigilant and assess risk factors for coexisting diseases and susceptibility to infection.

The main options for lupus nephritis are mycophenolate mofetil (MMF) and cyclophosphamide (CYC), often administered together with corticosteroids. Both drugs give rise to malformations, and are absolutely contraindicated in pregnancy. In addition, azathioprine (AZA) is often used with MMF as maintenance therapy. Tacrolimus might be used to manage lupus nephritis in pregnancy. These drugs are also frequently used for hematologic lupus.

Non-renal lupus management choices are dependent on the underlying cause of disease. Neuropsychiatric lupus is often managed using the drugs employed for renal disease. Hydroxychloroquine and immunosuppressants are used for musculoskeletal symptoms while methotrexate and biological drugs are used to control inflammatory arthritis.

In addition to these treatments, the immunomodulatory agent dapsone, along with biological drugs such as rituximab and belimumab, can be employed to manage skin manifestations.

Biological treatments for lupus can be divided into those that target B-cells and those that don’t. Rituximab selectively targets B-cells that have the surface marker CD20. While there is a widespread acceptance of rituximab for lupus treatment, some clinical trials have not reported successful results.

Belimumab also targets B-cells, and two clinical trials have shown that it is effective for lupus management. The trials, however, excluded patients with lupus nephritis and neuropsychiatric disease, and the drug is not approved for these patients.

The drug abatacept also targets interactions between B- and T-cells. The drug was evaluated in two clinical trials — in renal and non-renal lupus, respectively — but failed to show beneficial results. A fresh analysis of trial results in renal lupus, however, suggested that a too strict definition of treatment response was used, and the re-analysis showed that abatacept indeed had favorable effects in lupus nephritis.

Another approach to treatment is to lower interferon-a. The immune factor is elevated in lupus patients and has been associated with disease activity. Phase 3 clinical trials are planned to investigate if lowering interferon-a activity leads to a clinical response.

The antimalarial drug hydroxychloroquine is mainly used to treat musculoskeletal and skin features of lupus, but studies show that it might have a far wider spectrum of advantageous effects. The drug is associated with less frequent disease flares and reduced risk of organ damage accumulation. Moreover, it has beneficial effects on blood lipids and bone mineral density, and possibly reduces cardiovascular and thrombotic risk. While it is associated with a small risk of developing retinopathy, requiring monitoring, the drug might be a good choice to manage other lupus-associated health conditions.

Future clinical trials will likely provide a clearer picture of which biological agents are suitable for lupus treatment. Meanwhile, hydroxychloroquine holds its position as a crucial drug and evidence of its benefits continue to accumulate.