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Objective-To determine whether azathioprine can prevent relapse in ulcerative colitis.Design-One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.Setting-Outpatient clinics of five hospitals. Subjects-79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.Main outcome measure-Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.Results-For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0-5, 95% confidence interval 0 25 to 1-0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p<001). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.Conclusions-Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.

ObjectiveAxial spondyloarthritis (SpA) is a chronic inflammatory disease characterized by back pain and stiffness. The objective of this study was to determine whether golimumab is superior to placebo in patients with nonradiographic axial SpA.MethodsThis phase III, double‐blind, randomized, placebo‐controlled trial was performed to evaluate subcutaneous golimumab (50 mg) versus placebo in patients ages ≥18 years to ≤45 years who had active nonradiographic axial SpA according to the Assessment of SpondyloArthritis international Society (ASAS) criteria for ≤5 years since diagnosis, high disease activity, and an inadequate response to or intolerance of nonsteroidal antiinflammatory drugs. Patients were randomized 1:1 to receive golimumab or placebo subcutaneously every 4 weeks. The primary end point was 20% improvement according to the ASAS criteria (ASAS20) at week 16. Key secondary end points were an ASAS40 response, ASAS partial remission, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) index for sacroiliac (SI) joint inflammation (SPARCC score).ResultsOf the 198 patients randomized, 197 were treated (97 received golimumab, and 100 received placebo). The mean age of the patients was 31 years, and 57.1% were male. At baseline, the mean ± SD BASDAI was 6.5 ± 1.5, the mean ± SD ASDAS was 3.5 ± 0.9, and the mean ± SD SPARCC score was 11.3 ± 14.0. The primary end point, an ASAS20 response, was achieved by significantly more patients in the golimumab group compared with the placebo group (71.1% versus 40.0%; P < 0.0001). An ASAS40 response was also achieved by significantly more patients in the golimumab group compared with the placebo group (56.7% versus 23.0%; P < 0.0001). The incidence of adverse events did not differ meaningfully between groups.ConclusionPatients with active nonradiographic axial SpA treated with golimumab had significantly greater improvement in symptoms compared with patients treated with placebo. Golimumab was well tolerated and had a favorable risk/benefit profile.

Two cathepsin K inhibitors (CatKIs) were compared with alendronate (ALN) for their effects on bone resorption and formation in ovariectomized (OVX) rabbits. The OVX model was validated by demonstrating significant loss (9.8% to 12.8%) in lumbar vertebral bone mineral density (LV BMD) in rabbits at 13-weeks after surgery, which was prevented by estrogen or ALN. A potent CatKI, L-006235 (L-235), dosed at 10 mg/kg per day for 27 weeks, significantly decreased LV BMD loss ( p < .01) versus OVX-vehicle control. ALN reduced spine cancellous mineralizing surface by 70%, whereas L-235 had no effect. Similarly, endocortical bone-formation rate and the number of double-labeled Haversian canals in the femoral diaphysis were not affected by L-235. To confirm the sparing effects of CatKI on bone formation, odanacatib (ODN) was dosed in food to achieve steady-state exposures of 4 or 9 mM/day in OVX rabbits for 27 weeks. ODN at both doses prevented LV BMD loss ( p < .05 and p < .001, respectively) versus OVX-vehicle control to levels comparable with sham or ALN. ODN also dose-dependently increased BMD at the proximal femur, femoral neck, and trochanter. Similar to L-235, ODN did not reduce bone formation at any bone sites studied. The positive and highly correlative relationship of peak load to bone mineral content in the central femur and spine suggested that ODN treatment preserved normal biomechanical properties of relevant skeletal sites. Although CatKIs had similar efficacy to ALN in preventing bone loss in adult OVX rabbits, this novel class of antiresorptives differs from ALN by sparing bone formation, potentially via uncoupling bone formation from resorption. ß