Lupus Expert Calls for Better Research, Outcomes of Clinical Trials

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July 12, 2016 • By

The Rheumatologist

CHICAGO—A lupus expert recently issued a call for action to improve outcomes of lupus clinical trials, a field that has had so many failed potential therapies that he said it seems to be “cursed.”

Richard Furie, MD, chief of rheumatology at Northwell Health in New York, said at the ACR’s 2016 State-of-the-Art Clinical Symposium that the field has had “just three wins, and I can’t tell you how many losses.”

The three achievements he counted are the BLISS-52 and BLISS-76 (Belimumab in Subjects with Systemic Lupus Erythematosus) trials, which led to the approval of belimumab, and the maintenance phase of ALMS (Aspreva Lupus Management Study), which found that mycophenolate mofetil was superior to azathioprine for lupus nephritis (LN) maintenance therapy.1,2

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Pitfalls of Potential Lupus Diagnosis

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June 13, 2016 • By

The Rheumatologist

Spotting the signs of autoimmunity as early as possible is often viewed as a positive goal for rheumatologic research. The premise: Patients may begin treatment years before their disease is active and destroying joints and tissue.

Although much progress has been made in identifying early stages of rheumatoid arthritis pathogenesis, the clues are not as clear in systemic lupus erythematosus (SLE). Many patients who test positive for autoantibodies that could be signs of potential SLE, such as antinuclear antibodies (ANA), never actually develop the disease. Describing a patient as having potential SLE could cause unnecessary anxiety and medication prescription in these individuals, say two lupus researchers.

“Previous reports have shown that only about 20% of patients with potential SLE go on to develop definite SLE. So if we use potential SLE as a diagnosis, we would be over-treating the majority of these patients,” say Graciela S. Alarcón, MD, MPH, MACR, Jane Knight Lowe Emeritus Professor of Medicine at the University of Alabama at Birmingham, and Manuel F. Ugarte-Gil, MD, a rheumatologist at the Hospital Nacional Guillermo Almenara Irigoyen in Lima, Peru, in a joint, written response to questions from The Rheumatologist.

Unnecessary Treatment

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New SLE Drug May Allow Patients to Reduce Steroid Use

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December 16, 2015 • By Michele B. Kaufman, PharmD, CGP, RPh
The Rheumatologist

Anifrolumab for Moderate to Severe SLE
The efficacy and safety of anifrolumab (ANIFR), an anti-interferon receptor monoclonal antibody, was assessed in 305 adults with sero-positive moderate to severe systemic lupus erythematosus (SLE), despite standard-of-care medication. This study was a randomized, double-blind, placebo-controlled Phase 2 study.1

Patients received either 300 mg or 1,000 mg ANIFR intravenously or placebo every four weeks for 48 weeks. The primary endpoint was a composite of Systemic Lupus Erythematosus Responder Index [SRI4] response at Day 169 with sustained reduction in oral steroid use (less than 10 mg daily and less than the Day 1 dose, maintained between Days 85 and 169).

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Epratuzumab Results Disappointing, but Adalimumab Promising

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The Rheumatologist

August 19, 2015 • By

Epratuzumab is a monoclonal antibody targeting CD22, which modulates B cells. Epratuzumab is thought to bind to CD22, resulting in diminishedsystemic lupus erythematosus (SLE)–related hyperactivity of B cells without depleting them.

In each study, patients (n = 786 for EMBODY 1; n = 788 for EMBODY 2) received placebo or treatment with 2,400 mg epratuzumab over four, 12-week treatment cycles administered as 600 mg every week for four weeks or 1,200 mg every two weeks for four weeks. Patients were all receiving corticosteroids at the beginning of the studies, along with either epratuzumab or placebo. Immunosuppressant and antimalarial drugs were given per their standard therapy regimen.

Adalimumab Effective in Juvenile ERA
In other drug news, adalimumab was recently studied in a Phase 3, multicenter, randomized, double-blind trial in patients age 6 years to younger than 18 years withenthesitis-related arthritis (ERA) for 12 weeks (n = 46).2 Patients received 24 mg/m2 adalimumab (maximum dose of 40 mg every other week) or placebo, followed by adalimumab for up to 192 weeks in an open-label design. If a predefined worsening occurred, early escape to the open-label adalimumab treatment period was available at Week 4. Adverse events were evaluated throughout the study. The primary endpoint was the percentage change from baseline at Week 12 in the number of active joints with arthritis (AJC). At baseline, the mean patient age was 12.9 years, with a mean duration of ERA symptoms being 2.6 years. The mean AJC was 7.8 and the mean enthesitis count was 8.1.

At Week 12, there was a 63% reduction in the number of joints with active disease in the adalimumab-treated patients compared with placebo-treated patients (12% reduction). By Week 52, there was an 89% reduction from baseline in the number of joints with active disease. (All patients had been receiving adalimumab after Week 12.) By Week 52, 35% of patients had stopped taking non-steroidal antiinflammatory drugs, 15% had stopped taking corticosteroids, and 11% were no longer taking other disease modifying antirheumatic drugs (e.g., sulfasalazine or methotrexate).

The most common adverse effects were upper respiratory infections, injection site pain, gastroenteritis, ALT elevations, abdominal pain nausea and syncope. Serious adverse events included worsening of ERA and appendicitis.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

  1. UCB. News release: UCB announces Phase 3 clinical trial program for epratuzumab in systemic lupus erythematosus did not meet primary endpoint. 2015 July 28.
  2. Burgos-Varga R, Tse SML, Horneff G, et al. Adalimumab in pediatric enthesitis-related arthritis A randomized, double-blind, placebo-controlled, multicenter study of adalimumab in pediatric patients with enthesitis-related arthritis.Arthritis Care Res (Hoboken). 2015 Jul 20. doi: 10.1002/acr.22657. [Epub ahead of print]