Efficacy of lumiracoxib in osteoarthritis: a review of nine studies.

Lumiracoxib is a cyclooxygenase-2 selective inhibitor in development for the treatment of osteoarthritis (OA), rheumatoid arthritis and acute pain. We reviewed nine clinical studies of 1-52 weeks' duration demonstrating the efficacy of lumiracoxib in OA. Male and female patients aged > or = 18 years with primary OA of the hand, hip or knee received lumiracoxib, placebo or active comparators (diclofenac, celecoxib or rofecoxib). Lumiracoxib provided consistent reductions in OA pain intensity and improvements in the patient's global assessment of disease activity and functional status (assessed using the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire or the Australian/Canadian OA Hand Index). These results were superior to placebo and similar to the active comparators tested. In addition, lumiracoxib was consistently superior to placebo and generally similar to active comparators in terms of the new Outcome Measures in Clinical Trials and Osteoarthritis Research Society International criteria. These were used to provide a single measure of response to treatment, taking into account pain, the patient's global assessment of disease activity and functional status.

Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis.

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.

Mediation by HLA-DM of dissociation of peptides from HLA-DR.

Human leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region, and shares some homology with MHC class I and class II proteins. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.