Rituximab looks promising in lupus

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Oct 28, 2002

Rituximab looks promising in lupus

New Orleans, LA - The B-cell depleting therapy rituximab has attracted an

enormous amount of interest in rheumatology circles, as it offers a new

approach to the treatment of autoimmune disease and has already shown

promising efficacy in several disorders, including rheumatoid arthritis and

systemic lupus erythematosus. It featured in several presentations at the

American College of Rheumatology meeting, and clinicians flocked to hear

first-hand about how the drug handles.

Among the presentations was a poster detailing a phase 1/2 clinical trial in

18 SLE patients, which concluded that rituximab looks promising for lupus,

but it may need to be used in combination with other therapies, perhaps

high-dose steroids and/or other immunosuppressants [1].

The patients enrolled in the study had moderately active lupus; all

continued on treatment with prednisolone, and some were also taking

hydroxychloroquine (Plaquenil®, Sanofi-Synthelabo) and/or azathioprine

(Imuran®, Prometheus Laboratories). Rituximab was administered at 1 of 3

doses1 infusion of 100 mg/m2 (first 6 patients), 375 mg/m2 (next 6), and 4

weekly doses of 375 mg/m2 (final 6 patients).

Dr Anolick (University of Rochester Medical School, NY) and

colleagues reported that 10 patients showed a good depletion (<1%) of

peripheral B cells, and in these patients there was a significant clinical

response (measured on the SLE activity index, SLAM). The clinical responses

were most prominent in mucositis, acute skin lesions, and alopecia. However,

6 other patients had poor B-cell depletion, and in these patients there was

no significant change in the SLAM score.

Overall, serologies did not improve significantly, and in particular

anti-double-stranded-DNA titers did not decrease (with 1 exception), even in

subjects who depleted well for prolonged periods of time (6 to 9 months).

Also, there was a high level of human antichimeric antibodies (HACAs), found

in 25% of the low- and medium-dose groups. Anolick commented that this

finding is unprecedented in the lymphoma experience (for which rituximab is

already marketed). The consequences of these high levels of HACAs are

unknown, but experience with other monoclonal antibodies suggest that they

may be associated with an increased risk of infusion-related reactions or

with an increased clearance of the drug, she commented.

Among the adverse events reported were 3 infectious events, of which 2 were

serious. One patient had an abscess (S aureus) and developed sepsis and went

into respiratory arrest but made a full recovery. Another patient, who had a

past history of septic wrist a year before the trial, developed shingles, a

septic elbow, fasciitis, and then sepsis. There were also 2 cases of

thrombosis (lower extremity deep vein thrombosis and a transient ischemic

attack) and 2 inflammatory events (new diagnosis of Bell's palsy and

enlarged parotid gland).

These complications are not unusual in lupus patients, particularly with

active disease, Anolick commented. However, the severity of the 2 infectious

complications, despite the absence of an absolute correlation with B-cell

depletion, raises concern and warrants close monitoring, particularly in

patients with basis leukopenia or a history of severe infections, she added.

Overall, however, the safety and efficacy seen in this small trial were

good, and further study is warranted, she said. The group is now planning a

further trial and is considering how best to use rituximab in combination

with other therapies.