Another of my concerns relates to standardization to the treatment regimen. In fact, there were four different regimens of rituximab given, and seven steroid treatments (consisting of three preparations) at the time of study entry. Whether these differences influenced outcome is unknown, although a more uniform regimen would have simplified interpretation of the study. With respect to laboratory studies, the assessment appears to be extensive and includes the IgG index and IL-6 from cerebrospinal fluid, MRI, SPECT scan, and FTG–positron emission tomography. The analysis of costimulatory molecule expression also appears complete, with a reduction in functional molecule expression on B and T cells reported. From these findings, the authors suggest that rituximab may work by modulating B and T cell interaction via these molecules.
Despite the methodologic concerns I have noted, the study is important because it reports all 10 patients experienced clinical improvement, with six experiencing some radiologic improvement in at least one reported modality. (See Table 1) The results are certainly intriguing. However, because of the manner in which results are reported and the differences in the treatment regimens, it is difficult to draw firm conclusions about the value of rituximab in this setting. For now, I think I’ll keep rituximab in my back pocket for my patients with CNS lupus who are either unable to tolerate or in whom I would like to minimize use of other cytotoxic therapies, and in those patients not responding to more traditional therapies.
Clearly, the rheumatology community needs a well-conceived and -executed study to examine the clinical effects of rituximab for lupus CNS manifestations. I hope that either a large center or group of centers take on this challenge and provide a prospective study with well-defined patient groups, standardized imaging protocols, pre-defined follow-up criteria, and a control group. One possible protocol could randomize patients with severe CNS manifestations (seizures, coma, optic neuritis, transverse myelitis) to pulse steroids plus IV cytoxan therapy versus pulse steroids plus rituximab. Immunologic studies could also be performed so that we gain knowledge not only on clinical outcomes, but immunologic mechanisms and effects of this drug in lupus patients.
BACK PAIN
Timing of Herniated Disc Surgery
By David G. Borenstein, MD
Peul WC, van Houwelingen HC, van den Hout WB, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med. 2007;356:2245-2256.
Abstract
Background: Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within six weeks, but the optimal timing of surgery is not known.
