Progression of sacroiliitis in men and women according to the cohort of early axial spondyloarthritis (CORSAR) over 3 years of follow-up

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with predominant involvement of the sacroiliac joints (SIJ) and/or the spine. Despite the fact that the prevalence of axSpA is almost the same in men and women, there is evidence of a delay in diagnosis and a more severe course of the disease in females. The available reports on the progression of structural changes in the SIJ in men and women with early axSpA are contradictory. Meanwhile, the analysis of radiographic progression in the SIJ has fundamental importance both for timely diagnosis and for assessing the effectiveness of therapy in axSpA. Such studies have not yet been carried out in the Russian Federation.Objective: to assess the radiographic progression of sacroiliitis (SI) over 3 years in men and women with early axSpA.Material and methods. The study included patients from the cohort of early axSpA CORSAR, formed at the V.A. Nasonova Research Institute of Rheumatology. Currently, it includes 175 patients with axSpA. We analyzed the data of 64 patients, followed for at least 3 years. To assess the radiographic progression of the disease at baseline and after 3 years, the sum of X-ray stages of SI in the left and right SIJ was determined (the total stage of SI). Progression was assessed by the change in the total stage of SI in the right and left SIJ (0-8) during the observation period. We also calculated the proportion of patients with deterioration (increase in the total stage of SI by at least 1 stage), with improvement (decrease in the total stage of SI by at least 1 stage) and without progression. In order to fully exclude the error in measuring the radiographic progression of SI, we counted patients with “net” progression, that is, the proportion of patients with improvement was subtracted from the proportion of patients with deterioration.Results. Among 64 patients with early axSpA, there were 37 (57.8%) men and 27 (42.2%) women. For 3 years, the median of the total stage SI in men was 0 [0; 1], in women - 0 [0; 2] (p>0.05). When assessing the progression of the total stage SI over 3 years, no significant differences were found between the number of men and women with improvement, with deterioration, “net” progression and without progression. Men with early axSpA showed a higher level of C-reactive protein (CRP) at baseline, women had higher BASDAI and ASDAS CRP values after 3 years. In 8% of patients, there was a regression of X-ray signs of SI.Conclusion. The radiographic progression of SI in patients with early axSpA does not depend on gender and disease activity. In some patients with early axSpA, reverse development of structural damage to the SIJ is possible.

Role of clinical and biochemical inflammation in structural progression of patients with psoriatic arthritis

ObjectiveTo determine the contribution of clinical and biochemical inflammation to structural progression of patients with psoriatic arthritis (PsA).MethodsWe analysed patients from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial (infliximab vs placebo). We obtained total modified Sharp/van-der-Heijde Scores from baseline and year one images, and swollen joint counts (SJC) and levels of C reactive protein (CRP) throughout the second half of year 1 (5 measurements) from 74 placebo-treated patients. We computed radiographic progression, time-averaged SJC (taSJC) and CRP (taCRP) values and assessed their impact on structural progression by logistic regression analysis. We further categorised patients as ‘active’ (+) or ‘inactive’ (−) based on their taSJC (cut-off point: 2/66 joints) and taCRP (cut-off point: 0.5 mg/dL) and compared radiographic progression across three groups (double inactive, single active, double active).ResultsORs for progression were 1.24 (95 % CI 1.04 to 1.47; p=0.016) for taSJC and 6.08 (95 % CI 1.12 to 33.03; p=0.036) for taCRP. When predictors were dichotomised (+ vs −), differences were maintained between taSJC+ and taSJC− patients (1.05±3.21 and 0.56±2.30, respectively), as well as for taCRP+ vs taCRP− patients (1.14±3.23 and 0.05±2.37, respectively). Progression was intermediate in the presence of abnormalities of one but not the other inflammatory variable, indicating increasing radiographic progression with increasing inflammation (p=0.05).ConclusionIn patients with PsA, both clinical and biochemical inflammation have an impact on structural progression. Overall, progression is smallest in the absence of both clinical and biochemical inflammation, higher when either clinical or biochemical inflammation is present and highest with both clinical and biochemical inflammation.

Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years

Objective To evaluate the long-term effect of ixekizumab on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and to identify potential predictors of progression. Methods This study evaluates patients from COAST-V (NCT02696785, bDMARD-naive) and COAST-W (NCT02696798, TNFi-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with ixekizumab (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Results Among patients with evaluable radiographs who were originally assigned to ixekizumab (N=230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of non-progressors over 2 years was 89.6% if defined as mSASSS change from baseline <2 and 75.7% if defined as mSASSS change from baseline ≤0. Predictors of structural progression at year 2 (mSASSS change >0) were age ≥40, baseline syndesmophytes, HLA-B27 positivity and male gender. Week 52 inflammation in SPARCC spine was also a predictor of radiographic progression at year 2 in patients with MRI-data in COAST-V (N=109). Conclusion The majority of patients with r-axSpA receiving ixekizumab had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

Effects of secukinumab on bone mineral density and bone turnover biomarkers in patients with ankylosing spondylitis: 2-year data from a phase 3 study, MEASURE 1

Background Axial spondyloarthritis including ankylosing spondylitis (AS) is characterized by chronic inflammation and new bone formation in the axial skeleton. On the other hand, bone loss, osteoporosis and an increased risk of vertebral fractures is known to frequently occur in AS. In the MEASURE 1 study, the clinically efficacious interleukin-17A inhibitor secukinumab was shown to have limited radiographic progression through 4 years in patients with active AS. Here we present a post hoc analysis to evaluate the effect of secukinumab on bone mineral density (BMD) and bone turnover biomarkers over 2 years in this study. Methods BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. Spinal radiographs performed at baseline and Week 104 were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and analyzed in relation to BMD change, considering baseline syndesmophytes. Bone turnover biomarkers were assessed at baseline and at Weeks 52 or 104. Results Among 104 patients included in this analysis, 66% were male, with a mean (SD) age of 40.4 (12.3) years. In postmenopausal women and men ≥50 years of age (T-score), the proportion of patients having normal BMD at baseline and Week 104 were 54.5%/54.5% (lumbar spine), 31.6%/55.6% (total hip), and 42.1%/44.4% (femoral neck). Similarly, at baseline, the proportion of patients with osteopenia/osteoporosis was 31.8%/13.6% (lumbar spine), 57.9%/10.5% (total hip), 42.1%/15.8% (femoral neck), and 36.4%/9.1% (lumbar spine), 44.4%/0% (total hip) and 55.6%/0% (femoral neck) at Week 104, respectively. In premenopausal women and men < 50 years of age (Z-score), the proportion of patients having BMD below the expected range for age at baseline and Week 104 were 25.0%/21.2% (lumbar spine), 11.3%/17.8% (total hip), and 9.9%/8.9% (femoral neck). In relation to mSASSS change scores ≥2 over 2 years, the increase in lumbar spine BMD was not related to radiographic progression and syndesmophyte formation. No significant changes were observed in the bone turnover markers over time. Conclusion The high proportion of AS patients with diminished BMD was confirmed in this study. An increase of BMD in the lumbar spine after 2 years of secukinumab treatment in patients with AS was found that was probably unrelated to radiographic progression. No relevant effects of secukinumab on bone turnover biomarkers were documented. Trial registration MEASURE 1 (post hoc analysis) Clinicaltrials.gov, NCT01358175; Registered, 23 May 2011.