SAN ANTONIO, Texas – In an effort to help identify more effective ways of managing and assessing systemic lupus erythematosus (SLE), new research shows that autologous stem-cell transplant and rituximab show promise in refractory disease, and that an inexpensive test may be more accurate at gauging disease activity than 2 more expensive modalities.

A small trial shows that autologous stem cell transplantation (ASCT), followed by high-dose ablative chemotherapy, has promise as a treatment option for refractory SLE,¹ according to principal investigator Tobias Alexander, MD, a rheumatologist in the Division of Rheumatology and Clinical Immunology at University Hospital Charité in Berlin, Germany. "Our data show that ASCT can induce long-term and treatment-free clinical and serological remission in patients with refractory disease," he said in an interview at the annual meeting of the American College of Rheumatology. "This treatment may also resolve organ damage at advanced stages, such as proteinuria following lupus nephritis."

However, Dr. Alexander pointed out, 2 of the 6 patients who underwent treatment died; one of post-transplant aspergillosis and one of a pulmonary embolism that developed 38 months after transplantation and 17 months after being symptom-free. Also, one patient developed Hashimoto's thyroiditis 36 months after ASCT, and another patient was diagnosed with monoclonal gammopathy of undetermined significance (MGUS) 24 months after ASCT.

Therefore, Dr. Alexander said, the next challenges are to improve the safety of ASCT. After those issues have been addressed, investigators will need to demonstrate in a clinical trial that it is more effective than standard therapy in such cases.

Because this treatment strategy is being explored for several severe autoimmune diseases, Dr. Alexander and his co-investigators wanted to see if it was effective in severe SLE. After patients underwent this treatment, the investigators assessed disease activity with the SLE Disease Activity Index (SLEDAI) and monitored post-transplant organ involvement and serological response.

The patients all had long-lasting histories of severe SLE with multiple organ involvement, including the kidneys, brain, and heart. At a median follow-up of 48 months, 4 patients were in complete clinical remission accompanied by serological remission, with a complete disappearance of autoantibodies and a normalization of complement factors C3 and C4. The patient with relapsing SLE showed a change in the types of antibodies expressed after relapse. The patients with lupus nephritis proteinuria either normalized or showed a dramatic decrease in symptoms after treatment, Dr. Alexander said.

The rituximab (Rituxan) study enrolled 5 female SLE patients with organ-threatening disorders who were resistant to intensive conventional therapies, reported principal investigator Yoshiya Tanaka, MD, Professor and Chair of Internal Medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan. The patients received weekly doses of rituximab (375 mg/m² x2). All patients showed clinical improvement of SLE manifestations, including central nervous system involvement, nephritis, hemolytic crisis, cardiomyopathy, and sensory disturbance. All had a reduction in the SLEDAI, ranging from 2 points to 36 points. The efficacy lasted for 20 months, with patients able to decrease corticosteroid use.²

Dr. Tanaka said that the results from the pilot study were promising enough that he and his co-investigators are planning a Phase I-II study to begin next year. "We don't really have good choices for treatment of SLE," Dr. Tanaka said. "Our findings show promise for reducing B cells, because they play an important role in SLE."

In other research, principal investigator Luis Vilá, MD, and co-investigators found that C-reactive protein (CRP) levels are less predictive of disease activity than elevations in the erythrocyte sedimentation rate (ESR).³ "This finding was surprising," said Dr. Vilá, Professor of Medicine and Director of the Rheumatology Clinic at the University of Puerto Rico's Medical Sciences Campus in San Juan, Puerto Rico. "The results have practical implications for rheumatologists, because the ESR is a much less expensive test than the CRP test, and we found that it is more accurate," he said.

The investigators, based in Puerto Rico, Texas, and Alabama, recruited 449 patients with SLE and compared their CRP levels with measures of their disease activity, as well as with their ESR and anti-double strand DNA (anti-dsDNA). The goal of the study was to assess CRP's predictive ability. Surprisingly, they found that CRP was only weakly associated with SLE disease activity (P = 0.058), as was anti-dsDNA (P = 0.053). However, ESR was strongly associated with disease activity (P <0.0001).

References:

Alexander T, Massenkeil G, Gromnica-Ihle E, et al. Treatment of severe systemic lupus erythematosus (SLE) with autologous stem-cell transplantation: long-term clinical outcome in 6 cases. Presented at: Annual Meeting of the American College of Rheumatology; October 19, 2004; San Antonio, Texas. Abstract 1025.

Tanaka Y, Tokunaga M, Fujii K, et al. A pilot study of rituximab (anti-CD20) for refractory systemic lupus erythematosus: relevance of quantity and quality reduction of B cells to clinical efficacy. Presented at: Annual Meeting of the American College of Rheumatology; October 19, 2004; San Antonio, Texas. Abstract 1027.

Vilá LM, Alarcón GS, Calvo-Alén J, et al. Association of C-reactive protein with disease activity and damage accrual at initial evaluation in patients with systemic lupus erythematosus. Presented at: Annual Meeting of the American College of Rheumatology; October 19, 2004; San Antonio, Texas. Abstract 1013.