Background/Purpose:

Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment of  spondyloarthritis (SpA) which is frequently associated with inflammatory bowel disease. Biologic disease modifying anti-rheumatic drugs (bDMARDs) should be considered in patients with persistently high disease activity despite conventional treatments. Current recommendation suggests that NSAIDs should only be prescribed if patients are symptomatic due to the potential side effects when administered chronically. However, clinical trial data have suggested that the continuous use of NSAIDs in patients with an elevated CRP results in reduced progression of structural damage in comparison to on-demand use only.

The purpose of this study is to investigate the benefits and harms of NSAIDs when used with bDMARDs on the bony overgrowth and the bowel inflammation in a SpA animal model.

Methods:

ZAP-70W163C–mutant (SKG) mice were housed under specific pathogen free conditions. All of the mice were injected intraperitoneally with 1,3-glucan (curdlan). Mice were treated with celecoxib and/or etanercept (ETN). Clinical manifestations were scored and the expression of inflammatory molecules were examined. Arthritis, spondylitis, and ileitis were assessed histologically at 8-week experimental end points. A bone mineral density tests (BMD) were conducted as well.

Results:

Combination therapy of celecoxib with ETN significantly suppressed the morphology scores (MS) and the infiltration of inflammatory cells in the axial and peripheral joints (Table 1). However, ETN monotherapy did not show any efficacy and celecoxib tended to decrease the disease activity. The expression of myeloperoxidase (MPO) was decreased in peripheral and axial joints by celecoxib but not by ETN. The generation of osteophyte was inhibited by celecoxib but not by ETN in a bone CT. Interestingly, combination therapy of celecoxib with ETN showed an additive effect on the inhibition of new bone formation.

Next, we investigated the effect of celecoxib and ETN on ileitis of the SKG mice (Table 2). Celecoxib did not make any further harmful effects on ileitis, but ETN significantly aggravated the ileitis which was restored with combination therapy with celecoxib. In addition, we looked into a BMD of SKG mice depending on the treatment groups (Table 3). Celecoxib increased BMD while ETN decreased which was compensated by co-use of celecoxib.

Conclusion:

These results indicate that celecoxib has beneficial effects on the arthritis, ileitis, and bone mineral density when used with ETN in SKG mice. Further clinical studies are warranted.