Discontinuation of biologic therapy in patients with rheumatoid arthritis and ankylosing spondylitis: analysis from multicenter cohort study.

Despite of the availability of several effective bDMARDs, a significant proportion of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients discontinued bDMARDs. The aims of this study were to analyze causes of bDMARDs discontinuation in RA and AS included in the Moroccan registry RBSMR. A historical prospective multicenter cohort study based on the RBSMR database at 12 months of follow-up, which included 225 RA and 170 AS. Using T student, Mann-Whitney U, chi-squared or Fischer exact tests, baseline demographic and clinical features were compared between patients discontinuing bDMARDs and patients remaining on initiated bDMARDs or switching bDMARDs. Logistic regression models were used to identify factors associated with drugs discontinuation. 61 RA discontinued bDMARDs and 47 AS interrupted anti-TNF. The most common reasons for drugs discontinuation were adverse events (7.5%) in RA patients and social security reimbursement problems (16.8%) in AS. RA patients discontinuing bDMARDs were more frequently first-line biological drugs users, more frequently female and had more comorbidities and lower DAS28 CRP than RA patients remaining on initiated bDMARDs or switching bDMARDs (p < 0.001, p = 0.01, p < 0.001 and p < 0.001 respectively). Female sex and comorbidities were the significant predictors of bDMARDs discontinuation in RA patients. Higher baseline BASDAI had a protective role on anti-TNF interruption in AS patients. Adverse events and social security reimbursement problems were the main reasons for drugs discontinuation in RA and AS patients respectively. Female sex and comorbidities in RA patients, baseline BASDAI in AS patients impacted bDMARDs discontinuation in real-life settings.

Polymorphisms of HLA-A, -B, -Cw and DRB1 antigens in Moroccan patients with ankylosing spondylitis and a comparison of clinical features with frequencies of HLA-B*27.

Ankylosing spondylitis (AS) is very often associated with human leukocyte antigen (HLA), particularly HLA-B*27. However, the strength of this association and clinical features may vary in different ethnic groups. Our study aims to assess the distribution of HLA-A, -B, -Cw and DRB1 alleles in Moroccan patients with AS and to compare the clinical features of AS and the frequencies of HLA-B27 in patients from Morocco with other series. Seventy-five patients diagnosed with AS and assessed for clinical manifestations were selected and compared to 100 healthy controls. HLA class I and II antigens were typed by polymerase chain reaction sequence-specific oligonucleotide. HLA-B27 subtypes were studied by polymerase chain reaction amplification with sequence-specific primers. HLA-B27 was found in 64% of patients. It was positively associated with younger age at disease onset, family history, and uveitis while it had a negative association with late onset. Six B*27 subtypes were identified in the AS group. HLA-B*2705 and B*2702 were the most common observed subtypes. Among other HLA genes, a significant increase in the prevalence of HLA-Cw*02 and HLA-DRB*15 was found in AS patients. HLA-B27 is involved in the predisposition of AS in the Moroccan population. HLA-B*2705 and B*2702 were the predominant subtypes supporting previous reports in Caucasian spondyloarthropathies. Other HLA genes, HLA-Cw*02 and HLA-DRB1*15, seem to confer predisposing effect to the disease. However, the lower frequency of HLA-B27 compared to the literature in our study suggests the existence of different genetic and/or environmental factors in Morocco.

Vertebral fractures and abdominal aortic calcification in postmenopausal women. A cohort study.

INTRODUCTION: Vertebral fracture assessment (VFA) imaging with a bone densitometer can simultaneously detect prevalent vertebral fractures (VFs) and abdominal aortic calcification (AAC). OBJECTIVE: To study the relation between the prevalence of VFs using VFA in asymptomatic women and the prevalence and severity of AAC. DESIGN: This is a cross-sectional study. SETTINGS: Subjects were recruited in a third care center from asymptomatic women selected from the general population. PARTICIPANTS: We enrolled 908 post-menopausal women with a mean age of 60.9 years ± 7.7 (50 to 91) with no prior known diagnosis of osteoporosis or taking medication interfering with bone metabolism. PRIMARY AND SECONDARY OUTCOME MEASURES: Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. VFA images were scored for AAC using a validated 24 point scale. RESULTS: VFA images showed that 179 of the participants (19.7%) had at least one grade 2/3 VF, 81% did not have any detectable AAC whereas the prevalence of significant atherosclerotic burden, defined as AAC score of 5 or higher, was 12%. The group of women with 2/3 VFs had a statistically significant higher AAC score and higher proportion of subjects with extended AAC, and lower weight, height, and lumbar spine and hip BMD and T-scores than those without VFA-identified VFs. Multiple regression analysis showed that the presence of grade 2/3 VFs was significantly associated with age, BMI, history of peripheral fracture, AAC score ≥ 5 and densitometric osteoporosis. CONCLUSION: In post-menopausal women, extended AAC is independently associated with prevalent VFs regardless of age, BMI, history of fractures, and BMD.

Systematic vertebral fracture assessment in asymptomatic postmenopausal women.

INTRODUCTION: Recognition of vertebral fractures (VFs) changes the patient's diagnostic classification, estimation of fracture risk, and threshold for pharmacological intervention. Vertebral fracture assessment (VFA) enables the detection of VFs in the same session as bone mineral density (BMD) testing. OBJECTIVE: To study prevalence and risk factors of VFs using VFA in asymptomatic women and measure its effect on treatment recommendations. METHODS: We enrolled 908 postmenopausal women (mean age, weight and BMI of 60.9 ± 7.7 (50-91) years, 73.2 ± 13.2 (35-150) kg and 29.8 ± 5.3 (14.5-50.8) kg/m(2), respectively. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. RESULTS: VFs were identified in 382 patients (42.0%): 203 (22.3%) had grade 1 and 179 (19.7%) had grade 2 or 3. The prevalence of VFA-detected fractures globally increased significantly with age and as BMI and BMD declined. A fracture was identified on VFA in 63 (28.3%) women with normal BMD (8.5% had grade 2/3 VFs) and in 145 (38.5%) with osteopenia (15.7% had grade 2/3 VFs). Stepwise regression analysis showed that presence of VFs was independently related to age, BMI, number of parity, history of peripheral fracture and lumbar spine BMD. CONCLUSION: A high proportion of women with asymptomatic VFs would not receive treatment if screening were based only on BMD evaluation. Our results support the recommendation to enlarge the indications of VFA in the presence of risk factors such as age over 60, multiparity, history of peripheral traumatic fractures and low BMI.

Vertebral fracture assessment in asymptomatic men and its impact on management.

INTRODUCTION: Recognition of vertebral fractures (VFs) change the patient's diagnostic classification, estimation of fracture risk, and threshold for pharmacological intervention. Vertebral fracture assessment (VFA) enables the detection of VFs in the same session as bone mineral density (BMD) testing. OBJECTIVE: To study prevalence and risk factors of VFs using VFA in asymptomatic men and measure its impact on patients' management. METHODS: We enrolled 791 men aged between 45 and 89 (mean age, weight and BMI of 62.4±8.6) (45 to 89) years, 74.9±12.7 (40 to 163) and 26.3±4.0 (16.6 to 43.8) kg/m(2), respectively. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. RESULTS: VFs were identified in 318 (40.3%): 206 (26.0%) had grade 1 and 112 (14.2%) had grade 2 or 3. As would be expected, the prevalence of VFA-detected fractures globally increased significantly with age and as BMI and BMD declined. A fracture was identified on VFA in 85 (32.4%) of men with normal BMD (6.9% had grade 2/3 VFs) and in 144 (35.8%) with osteopenia (11.7% had grade 2/3 VFs). Stepwise regression analysis showed that presence of VFs was independently related to the osteoporotic status (OR=4.761, 95%CI [2.956-7.668]; p<0.0001) and current smoking (OR=1.717, 95%CI [1.268-2.323]; p=0.002). CONCLUSION: Our results support the recommendation to enlarge the indications of VFA to all the men referred for DXA measurement.

Prevalence and risk factors of osteoporosis and vertebral fractures in patients with ankylosing spondylitis.

UNLABELLED: Ankylosing spondylitis (AS) is characterized by inflammation of the entheses and paravertebral structures, leading in time to bone formation at those sites. As well, vertebral bone loss is also a recognized feature of AS Objective: To calculate the prevalence and risk factors of osteoporosis and vertebral fractures in patients with AS. METHODS: Eighty patients with AS were enrolled in the study. Clinical, biological and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), ESR and C-reactive protein (CRP), Bath AS Radiology Index (BASRI) and modified stoke AS spine score (mSASSS). BMD of the hip and spine was measured and vertebral fractures were defined using a combination of Genant semiquantitative (SQ) approach and morphometry by VFA (fracture vertebral assessment). RESULTS: The years+/-11.8. The mean BMI was 22.8 kg/m(2)+/-4.1 and the mean disease duration was 10.8 years+/-6.6. Prevalence of osteoporosis was 25%. 18.8% of patients had a vertebral fracture (grades 2 and 3). Factors associated with osteoporosis were low weight and BMI and longer disease duration, higher ESR, CRP, BASFI and BASDAI. Vertebral fractures were associated with advanced age, longer disease duration, higher BASFI, BASRI and mSASSS and reduced BMD and T-score at the hip site, presence of osteoporosis at any site. Multiple logistic regression analysis (Table 4) revealed that parameters significantly associated with osteoporosis were BASDAI (OR=1.05, 95% confidence interval [CI]: 1.03-1.09); disease duration (OR=1.13, 95%CI: 1.03-1.25); and BMI (OR=0.82, 95%CI: 0.69-0.93). The presence of VFs (grades 2 and 3) were independently associated with disease duration (OR=1.50, 95%CI: 1.07-2.10); and mSASSS (OR=1.17, 95%CI: 1.05-1.30). CONCLUSION: Osteoporosis is common in patients with AS and seems to be related to disease activity while vertebral fractures appear to be related to the duration and structural severity of the disease rather than BMD.

Vertebral fracture assessment in Moroccan women: prevalence and risk factors.

INTRODUCTION: Vertebral fracture assessment (VFA) is a fast, low-radiation technique which produces images that are of sufficient quality to be used to diagnose the presence of vertebral deformity consistent with fracture. OBJECTIVE: To study prevalence and risk factors of vertebral fractures using VFA in asymptomatic Moroccan women. METHODS: The study cohort consists of a population of 328 consecutive women aged over 50 (mean age, weight and BMI of 65+/-6.5 (50-84) years, 72.0+/-12.8 (42-125) and 29.4+/-5.0 (17.1-45.8)kg/m(2), respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained by two technologists using a GE Healthcare Lunar Prodigy densitometer. Vertebral fractures were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. RESULTS: 68% of vertebrae from T4-L4 and 75% from T8-L4 were adequately visualized on VFA. Vertebral fractures (grades 2 or 3) were detected in 25.6% (84/328) of these women. Thirty-two of women with VFA-identified fracture (38.0%) had only a single vertebral fracture, while the other 61.9% had two or more. Fractures were most common in the mid-thoracic spine and at the thoraco-lumbar junction. As would be expected, the prevalence of VFA-detected fractures increased with age and as BMD declined. Stepwise regression analysis showed that presence of vertebral fracture was mainly related to the spine osteoporotic status, age older than 65, history of peripheral fracture and more than six parities. CONCLUSION: Vertebral fractures are common in asymptomatic Moroccan women and are related to age, low BMD, history of fracture and multiparity.

Bone mineral density of the spine and femur in a group of healthy Moroccan men.

BACKGROUND: Bone mineral density (BMD) measurements using dual-energy X-rays absorptiometry (DXA) are widely used to diagnose osteoporosis and to assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the male Moroccan population. AIM: To establish reference values for the healthy Moroccan male population and to compare them with those for Caucasian and Arab males, and to study the impact of different curves implemented in the DXA system on the diagnosis of osteoporosis. METHODS: A cross-sectional study of 592 Moroccan men, recruited from the area of Rabat, the capital of Morocco, aged between 20 and 79 years was carried to establish reference values of bone mineral density. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative taken by US, European, Iranian, Lebanese, and Saudi men over six decades of age. Impact on osteoporosis diagnosis according to the WHO criteria using the personalized curve and US (NHANES), European and Middle-East reference curves (as implemented in the Lunar densitometers) was studied. RESULTS: Our results showed that the Moroccan men showed the expected decline in BMD at both sites with age after peaking at 20-29 years age group. Every anatomical region has a different rate of bone loss: lumbar spine (0.3% per year) femoral neck (0.6%), trochanter (0.3%), and total hip (0.4%). The lumbar spine and femoral subregions BMD exhibited increases from 0.3 to 0.5% per kilogram of body weight. In the spine, the US/European Lunar reference values classified a larger proportion of men as osteoporotic (18.1% vs. 7.4%) while using the Arabic Lunar reference values, only 7.8% were classified as osteoporotic. However, using Arabic curve for the femurs resulted in underdiagnosis of osteoporosis (1.8% vs. 6.0%), whereas the US/European Lunar reference values classified men as osteoporotic in 3.9% and 5.3% respectively. DISCUSSION: In comparison with the other Countries, the spine BMD of Moroccan men were slightly lower than Iranian's, Europeans and Brazilians but higher than the Saudi and Lebanese males. We found BMD values taken at the lumbar spine to be around 4% lower than European values between ages 50 and 59 years, and 10% lower for older subjects. These values were 4-6% higher than Saudis/Lebanese values between ages 20-39. For older subjects, Moroccan values were more than 10% higher than Saudis and almost similar to Lebanese. Femoral neck BMD values were 8% higher in young adults (age 20-39 years) to US/Saudis/Lebanese values, but about 10% lower in ages over 60 to US values whereas it was similar to Saudis and Lebanese values. CONCLUSION: Our study emphasises the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.

Performance of calcaneus quantitative ultrasound and dual-energy X-ray absorptiometry in the discrimination of prevalent asymptomatic osteoporotic fractures in postmenopausal women.

Due to its low cost, portability, and nonionizing radiation, quantitative ultrasound (QUS) of the heel is an alternative to the measurement with dual X-ray absorptiometry (DXA) in the evaluation of bone status. The objective of the study is to compare in asymptomatic postmenopausal women the ability of QUS and DXA to discriminate between those with and without prevalent vertebral fractures (VFs). The study cohort consists of a population of 295 postmenopausal women aged between 60 and 84 (mean age, weight and BMI of 66.3 years, 72.0 kg and 29.4 kg/m(2), respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained by two technologists using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. All women had a calcaneous QUS examination. The mean age of the women in our sample was 66.3 (+/-5.3) years, ranging from 60 to 84 years. Eighty-seven (29.3%) women had VFs Genant grade 2 and 3. Patients with VFs had an age and a number of years of menopause higher to those without VFs, but showed lower height, weight, and BMI. All densitometric and ultrasonometric measurements were significantly reduced in women with VFs. The intercorrelations of BMD at different sites were high, and the correlations of BUA with BMD were lower. BUA correlated weakly with total hip BMD (r = 0.36), lumbar spine BMD (r = 0.32), and much less with femur BMD (r = 0.30); all correlations were significant (P < 0.01). Analysis of the AUC for the ROC curves showed lumbar spine T-score below -2.5 to provide consistently the highest AUC (0.64). Age-adjusted ORs after correction for confounding variables (years of menopause, weight, height, and BMI) for QUS and BMD measurements showed that only lumbar spine T-score below -2.5 could predict significantly the presence of VFs (OR, 1.94; 95%CI, 1.02-3.41). Lumbar spine BMD (and not QUS) was able to discriminate asymptomatic postmenopausal women with prevalent VFs from women without VFs and independently contributed to determining the association with fracture. The combination of QUS and BMD did not improve the diagnostic ability of either individual technique.

Discordance between hip and spine bone mineral density measurement using DXA: prevalence and risk factors.

BACKGROUND: Diagnostic discordance for osteoporosis is the presence of different categories of T-scores in 2 skeletal sites of an individual patient, falling into 2 different diagnostic categories identified by the World Health Organization classification system. OBJECTIVES: To evaluate the prevalence and risk factors for T-score discordance between spine and total hip measurement sites. METHODS: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database of 3479 patients referred to a community-based outpatient osteoporosis testing center. Dual-energy x-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hips for all cases. Minor discordance was defined as present when the difference between 2 sites was no more than 1 World Health Organization diagnostic class. Major discordance was present when 1 site is osteoporotic and the other is normal. Subjects with incomplete data were excluded. RESULTS: In 3479 participants (2871 women; mean age, 55.7 +/- 11.9 years), concordance of T-scores, minor discordance, and major discordance were seen in 54, 42, and 4%, respectively. In multivariate logistic regression analysis, age, menopause, and obesity were identified as risk factors against T-score discordance. CONCLUSION: Densitometrists and clinicians should expect that at least 4 of every 10 patients tested by DXA to demonstrate T-score discordance between spine and total hip measurement sites. T-score discordance can occur for a variety of reasons related to physiologic and pathologic patient factors as well as the performance or analysis of DXA itself.

Drug-induced lupus-like syndrome in ankylosing spondylitis treated with infliximab.

Specific antagonists of tumour necrosis factor (TNF-alpha) have rapidly gained popularity for the treatment of rheumatoid arthritis and ankylosing spondylitis (AS). Reported side effects from these agents include drug-induced autoimmune disorders. The monoclonal antibody against TNF-alpha, infliximab, has been associated with induction of systemic lupus erythematosus (SLE) in only one patient with AS in the literature. However, there have been no published reports of drug induced lupus-like syndrome (LLS) with positive anti-histone antibodies. We describe a 59-year-old woman with a 12-year history of refractory axial AS who developed signs and symptoms of LLS during treatment with infliximb with positive antinuclear and anti-histone antibodies. On diagnosis of LLS, infliximab was discontinued and the LLS-related symptoms promptly resolved.