ObjectivesApremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.MethodsIn the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16.ResultsAt week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.ConclusionsApremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated.Clinical trial registration numberNCT01172938.

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Objective To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors ( TNF i). Methods In this phase III randomized, double‐blind, placebo‐controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNF i and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ ASAS ] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80‐mg subcutaneous ixekizumab every 2 weeks ( IXE Q2W) or 4 weeks ( IXEQ4W ), with an 80‐mg or 160‐mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria ( ASAS 40) at week 16. Secondary outcomes and safety were also assessed. Results A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS 40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events ( AE s) with ixekizumab treatment were more frequent than with placebo. Serious AE s were similar across treatment arms. One death was reported ( IXEQ2W group). Conclusion Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNF i yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.

Physical activity is known to have an anabolic effect on bone tissue. It has been shown to increase the bone mineral density (BMD) in young adults, as well as in teenagers. But there is little information about the effect of intensive physical activity in childhood, particularly at the prepubertal stage. To examine the influence of an early intensive physical training on BMD, we have studied a group of elite prepubertal girls, at the starting phase of their peak bone mass acquisition. Subjects were engaged either in sport requiring significant impact loading on the skeleton, or in sport without impact loading. Forty-one healthy prepubertal girls took part in this study. The sport group consisted of 10 swimmers (10.5 +/- 1.4 years old) and 18 gymnasts (10.4 +/- 1.3 years old), who had performed 3 years of high-level sport training (8-12 h per week for swimmers, 10-15 h per week for gymnasts). Thirteen girls (10.7 +/- 1 years old) doing less than 3 h per week of physical activity served as a control group. BMD measurements were done using dual-energy X-ray absorptiometry. There was no statistical significant difference between groups as regards age, body height and weight, and body composition. There was no statistical significant difference between swimmers and controls for all the BMD measurements. Mean BMD in gymnasts was statistically higher than in the control group for mid-radius (+15.5%, p < 0.001), distal radius (+33%, p < 0.001), L2-4 vertebrae (+11%, p < 0.05), femoral neck (+15%, p < 0.001) and Ward's triangle (+15%, p < 0.01). Moreover, in gymnasts, BMD at radius, trochanter and femoral neck was above normative values. We conclude that physical activity in childhood could be an important factor in bone mineral acquisition in prepubertal girls, but only if the sport can induce bone strains during a long-term program: gymnastics has such characteristics, unlike swimming. Such acquisition could provide protection against risks of osteoporosis in later life, but this remains debatable.

Subchondral bone changes were mainly observed in advanced OA, when cartilage has been deleted and preserved in adjacent area. These data suggest that subchondral bone changes would be rather secondary to the cartilage deterioration than a primitive mechanism of OA. Nevertheless, longitudinal data could bring more accurate conclusions.