Rheumatoid Arthritis: Jackson M

Mason U, Aldrich J, Breedveld F, Davis CB, Elliott M, Jackson M, Jorgensen C, Keystone E, Levy R, Tesser J, Totoritis M, Truneh A, Weisman M, Wiesenhutter C, Yocum D, Zhu J. · GlaxoSmithKline Pharmaceuticals, Greenford, Middlesex, UK. · J Rheumatol. · Pubmed #11838838 No free full text.

Abstract: OBJECTIVE: Double blind studies were conducted with the anti-CD4 monoclonal antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis (RA), to confirm preliminary evidence of efficacy and safety from open. uncontrolled studies. METHODS: We enrolled 136 and 186 patients into 2 consecutive, randomized, double blind trials, with similar populations [apart from inclusion of disease modifying antirheumatic drug (DMARD)-naïve patients in Study 2]. Patients received 4 weeks intravenous placebo or keliximab [40, 80, 120, or 140 mg twice weekly (bw), or 240 mg once weekly (ow)].The primary endpoint was the American College of Rheumatology (ACR) 20 response criteria, one week after the end of treatment. RESULTS: ACR 20 response rates in Study I were 19%, 42%, 51%*, and 69%* (*p < 0.05 compared to placebo), with placebo, 40, 80, or 140 mg keliximab bw, respectively. The response rates in Study 2 were 30%, 39%, 46% and 47% with placebo, 80 or 120 mg bw, or 240 mg keliximab ow, respectively. In the 2 studies, there was a dose dependent increase in peripheral blood CD4+ T cell coating with keliximab, but a different pattern of CD4 depletion was seen. While only 12% of keliximab treated patients in Study I had CD4 counts below 250 cells/mm3 at the end of the treatment period, 47% fell below this level in Study 2. Clinical response was not correlated with CD4 depletion, but was correlated with CD4+ T cell coating with keliximab. CONCLUSION: Coating of peripheral blood CD4+ T cells with keliximab, but not CD4 depletion, is a determinant of clinical response.

Canvin JM, Bernatsky S, Hitchon CA, Jackson M, Sowa MG, Mansfield JR, Eysel HH, Mantsch HH, El-Gabalawy HS. · Arthritis Centre, University of Manitoba, RR-149, 800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada. · Rheumatology (Oxford). · Pubmed #12509617 links to  free full text

Abstract: OBJECTIVES: It is difficult to determine the extent of synovial involvement early in the course of rheumatoid arthritis. A spectroscopic technique was used to characterize the synovium of the small finger joints in both early and late rheumatoid arthritis. This synovium was also compared against normal joints. METHODS: Near-infrared spectroscopy assesses the absorption of near-infrared light by specific joints, giving a characteristic "fingerprint" of the properties of the underlying tissues. Triple measurements by infrared spectroscopy were taken at the bilateral second and third metacarpophalangeal joints. Multivariate analysis was applied. RESULTS: Analysis was able to demonstrate relationships between the specific sources of spectral variation and joint tenderness or swelling as well as radiographic damage. Further use of multivariate analysis allowed recognition of the spectral patterns seen in early disease vs late rheumatoid arthritis and correct classification of over 74% of the joints. CONCLUSIONS: The spectral regions where differences occurred were in the absorption bands related to tissue oxygenation status, allowing the provocative implication that this technique could be detecting ischaemic changes within the joint. Near-infrared spectroscopy may thus be able to provide us with some information about the biochemical changes associated with synovitis.