Here's an extract from a paper on NSAIDs and AS with reference to the HLA-27 gene. It is from the website www.hopkins-arthritis.som

Ankylosing Spondylitis
Abstract 518 Inhibition of Radiographic Progression in Ankylosing Spondylitis (AS) by Continuous Use of NSAIDs
Wanders, van der Heijde, Dougados
summarized by Jon Giles, M.D. and Joan Bathon, M.D.

NSAIDs remain first line therapy for AS and are associated with rapid improvement in axial signs and symptoms. The potential for this class of drugs to modify/slow disease has never been shown, though few rigorous evaluations have been performed. Here, Wanders et al hypothesize that continuous use of NSAIDs will reduce progression of structural damage in AS compared to intermittent, on-demand use.

Methods: This was a two-year treatment study in which subjects fulfilling modified New York criteria for AS were randomized into one of two treatment groups. Group 1 (continuous NSAID use) was assigned to receive celecoxib 100 mg BID. The dosage could be increased to 200 mg BID or an alternative NSAID could be used for severe symptoms. Group 2 (on-demand use) was assigned to receive celecoxib per patient demand for symptoms. A change to an alternate NSAID was allowed for severe symptoms. Participants underwent lateral plain radiographs of the cervical and lumbar spine at baseline and after two years. Radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (SASSS) by a blinded observer. The primary endpoint was change in SASSS at two years.

Results: 215 patients were randomized, 111 into the continuous NSAID group and 104 into the on-demand NSAID group. Mean age in both groups was approximately 40 years. 70% were male. 80% were HLA B-27 positive. Groups were well matched to baseline characteristics, except for disease activity, which was slightly higher in the on-demand NSAID group.

96 participants in the continuous NSAID group completed the study. At two years, 68 were using celecoxib while 28 had changed to an alternate NSAID. The average dose of celecoxib in this group was 243 mg/day. 86 participants in the on-demand NSAID group completed the study. At two years, 67 were using celecoxib while 19 had changed to an alternate NSAID. The average dose of celecoxib in this group was 201 mg/day.

Efficacy Endpoints — For subjects with complete radiographs (n=76 in the continuous NSAID group, n=74 in the on-demand NSAID group), the mean change in SASSS was 0.4 and 1.5 for the continuous NSAID and on-demand NSAID groups, respectively. BASDAI scores were similar in both groups over two years.

Safety Endpoint — GI symptoms were equivalent in both groups. Hypertension was higher in the continuous NSAID group.

Conclusions: Continuous NSAID use in AS is superior to intermittent, on-demand NSAID use in slowing radiographic progression over two years. Continuous NSAID is as safe as intermittent NSAID.

Editorial Comments: These results are quite surprising since most rheumatologists have assumed that NSAIDs do not slow progression of any inflammatory joint disease. Well designed treatment and radiologic studies of NSAIDs or most DMARDs in AS have been few and far between. However, the current findings are even more surprising given that the mean doses of celecoxib taken by the two groups are only modestly different. Cox-2 has been shown to regulate differentiation of mesenchymal cells to osteoblasts. Thus, slowing syndesmophyte formation via Cox-2 inhibition with NSAIDs is the proposed mechanism of action.

A critical question, as in RA, is whether these radiographic differences in progression will be associated, in the long-term, with better functional and quality-of-life outcomes. It is unlikely that monotherapy with an NSAID or Cox-2 inhibitor (without concurrent DMARD therapy) will be endorsed by most rheumatologists except in the mildest cases of AS.

hope this is of use

8o