By Phoebe Starr
Washington, DC—The goal of treating lupus is to induce improvement and maintain it, said Bevra Hahn, MD, Chief, Department of Rheumatology and Arthritis, University of California at Los Angeles. Improvement can be induced in 75% of patients with currently available therapies, some of them off-label, she told listeners at the 2012 meeting of the American College of Rheumatology.
“New agents for lupus hold the promise of effective treatment for patients who are not doing well on their current therapy or have a lot of side effects,” she stated.
Antimalarials plus nonsteroidal anti-inflammatory drugs are the mainstays of treatment, Dr Hahn said, but most patients will have a suboptimal response and require additional treatments.
Anecdotal evidence supports the use of low-dose corticosteroids for patients who do not respond to initial therapy. Two small trials suggested that the addition of methotrexate may be helpful in patients with nonrenal lupus and suboptimal response to initial therapy.
“In my opinion, azathioprine [Imuran] appears to be helpful in about 50% of patients,” Dr Hahn said. Leflunomide (Arava) is another option; one study showed this drug achieved improvement in 30% of patients, and improvement was sustained while taking the drug.
Other off-label options are mycophenolate mofetil (CellCept), belimumab (Benlysta), abatacept (Orencia), tumor necrosis factor inhibitors, and tocilizumab (Actemra) for lupus patients who have arthritis, but it is difficult to get reimbursement for these agents, she continued.
Mycophenolate mofetil was as equally effective as intravenous cyclophosphamide (Cytoxan) for extrarenal manifestations of lupus in one study, but the benefits would have to outweigh the risks of this drug. Abatacept appears to be effective in some patients with polyarticular manifestations of lupus, Dr Hahn added.
Belimumab is effective in treating patients with systemic lupus erythematosus (SLE), she stated. In a total of 1684 patients who were studied in phase 3 clinical trials of SLE, 51% responded to belimumab versus 38% for placebo at 1 year (P <.001). Belimumab reduced flares (including renal flares), reduced fatigue, and improved quality of life.
Adverse events (AEs) of belimumab include infusion-related reactions in approximately 10% of patients, and this can be serious in approximately 1% of patients. Antihistamine and acetaminophen are advised before the first 2 infusions as prophylaxis, Dr Hahn said.
In the large phase 3 clinical trials of belimumab, the rate of AEs was similar with belimumab and placebo—approximately 15%. Serious infections were reported in approximately 6% of patients in the belimumab cohort. Other relatively common side effects include headache, low-grade fever, increased arthralgia, nausea, and suicidal thinking.
“Reconsider using belimumab in a patient with depression,” she stated.
The recommended dose of belimumab is 10 mg/kg intravenously at days 0 and 2, at 4 weeks, and once monthly thereafter. Response is slow and can take up to 6 months. Patients with improved serum complement levels by 8 weeks are likely to respond. Stopping the use of belimumab should be considered after 6 months if there is no response.
Patients who are antithyroglobulin antibody positive are candidates for belimumab, as are patients with active SLE despite standard therapy.
Rituximab (Rituxan) has achieved response rates of 70% to 80% in open-label trials, and responses are seen in patients who fail with other treatments, Dr Hahn said.
However, 2 prospective randomized trials found no difference between rituximab and placebo in patients receiving background immunosuppressive therapy.
“Post-hoc analysis showed significantly fewer flares in patients with nonrenal lupus who took rituximab. Some patients will have a good response to this drug,” Dr Hahn noted.
Neuropsychiatric criteria have been incorporated into the Systemic Lupus International Collaborative Clinics criteria for central nervous system (CNS) lupus, which refers to neurologic and psychiatric symptoms in lupus. Symptoms include seizures, psychosis, mononeuritis, myelitis, peripheral neuropathy, cranial neuropathy, and acute confusional state.
“I believe worsening depression is a symptom of oncoming lupus flare,” Dr Hahn stated.
The treatment of CNS lupus is an evolving area. First, determine whether the symptoms are caused by lupus, which will be the case in approximately 50% of patients, she said. Then determine whether the symptoms are vascular or nonvascular and inflammatory versus noninflammatory with laboratory tests and magnetic resonance imaging (MRI).
The European League Against Rheumatism guidelines for CNS lupus include MRI analysis and treatment with steroids plus immunosuppressive therapy. Other causes of neuropsychiatric symptoms should be excluded. If stroke or transient ischemic attack occur, treat these and other cardiovascular conditions as you would patients without lupus, she said.