The Effect of Anti-rheumatic Drugs on the Skeleton.

The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of "established therapeutics". An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.

Coexistent subclinical hypothyroidism is associated with an increased risk of new cardiovascular events in rheumatoid arthritis: an explorative study.

Objective: Autoimmune thyroid disease often coexists with rheumatoid arthritis (RA) and is associated with elevated cardiovascular (CV) risk. However, studies in RA patients are scarce. Our aim was to investigate whether autoimmune thyroid disease increases the risk of new cardiovascular disease (CVD) in RA.Method: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 323 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity, and mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) for new CVD and adjusted for age, gender, smoking, prevalent CVD, thyroxine replacement therapy, and RA duration.Results: Of the 323 participants, 65.3% were female, and mean ± sd age was 63 ± 7 years. At baseline, 8.1% were hypothyroid (n = 26, 16 clinical, 10 subclinical), 6.8% hyperthyroid (n = 22, 13 clinical, 9 subclinical), and 85.1% (n = 275) euthyroid. A new CV event developed in 94 patients (29.1%) during follow-up. Compared to euthyroid patients, the HR adjusted for age, gender, and prevalent CVD was 2.83 [95% confidence interval (CI) 1.13-7.09; p = 0.026] for subclinical hypothyroidism. Further adjustment for smoking, thyroxine replacement therapy, and RA duration resulted in an HR of 3.0 (95% CI 1.19-7.54; p = 0.02) for CV events in patients with subclinical hypothyroidism.Conclusion: There was no difference in CVD between RA patients with hypothyroidism and hyperthyroidism versus euthyroid patients. Coexistence of subclinical hypothyroidism with RA is associated with a higher occurrence of new CV events. Treatment trials are needed to determine whether thyroxine supplementation can further improve CV outcome in these patients.

Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study Amsterdam population: a validation study.

Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

Increased progression of carotid intima media thickness in thyroid peroxidase antibodies-positive rheumatoid arthritis patients.

OBJECTIVE: Autoimmune diseases such as rheumatoid arthritis (RA) and hypothyroidism tend to cluster, and this coexistence amplifies the elevated cardiovascular risk in RA. Whether thyroid peroxidase antibodies (TPOabs) are associated with increased cardiovascular disease (CVD) risk has not been studied extensively. Therefore, this study determined firstly the prevalence of TPOabs in RA and secondly whether TPOabs were associated with CVD. Moreover, this study explored whether TPOabs were related to RA characteristics. DESIGN AND METHODS: Data from the CARRÉ Study, an ongoing study investigating CVDs and its risk factors in RA (n=322), was used to ascertain the prevalence of TPOabs in RA patients. In addition, cardiovascular and RA disease characteristics were compared between TPOabs-positive and -negative patients at baseline and at a second visit after 3 years. RESULTS: TPOabs were present in 47/322 (15%) RA patients and TSH levels were higher in TPOabs-positive patients (1.40 mU/l) compared with TPOabs-negative patients (1.26 mU/l, P=0.048). At baseline and after 3 years no association was observed between TPOabs and (risk factors for) CVD. Regression analyses revealed a significantly larger progression of carotid intima media thickness (cIMT; ß=0.13 mm) in TPOabs-positive compared with TPOabs-negative patients independent of risk factors for cIMT progression. RA disease activity scores (DAS28) were higher in TPOabs-positive compared with TPOabs-negative patients (4.4 vs 3.8 P=0.018). CONCLUSIONS: TPOabs were associated with increased cIMT progression. Moreover, an association between TPOabs and DAS28 was observed. Hence, TPOabs seems to have a role in the amplified cardiovascular risk in RA patients.

Work ability: a new outcome measure in rheumatoid arthritis?

OBJECTIVES: To assess the relationship between disease activity and work ability, quality of life (QoL), and fatigue in patients with RA during a 12-month course of the tumour necrosis factor (TNF)-blocking agent adalimumab. METHODS: RA patients in the working age category who started treatment with adalimumab were included consecutively and followed up for 12 months. Generalized estimating equation (GEE) analyses were used to study relationships between disease activity and the outcome variables work ability, QoL, and fatigue at baseline, 6 months, and 12 months. Disease activity was measured using the 28-joint Disease Activity Score (DAS28), quality of life was assessed with the Rheumatoid Arthritis-specific Quality of Life instrument (RAQoL), and fatigue was assessed using the Checklist Individual Strength (CIS) questionnaire and the Need for Recovery scale (NFR). RESULTS: After 1 year, markedly improvement was seen not only in the DAS28 (from 5.2 +/- 1.2 to 3.1 +/- 1.6) but also in work ability, RAQoL, and work-related fatigue, which improved by 50, 29, and 34%, respectively. At all three time points strong significant associations were observed between DAS28 and work ability, RAQoL, and work-related fatigue and this relationship remained strong after adjustment for confounders. CONCLUSIONS: Disease activity was associated with QoL, work-related fatigue, and work ability in a group of RA patients treated with adalimumab for 1 year. As improvement in these factors influences work participation positively and work ability measures more than health status, the current results suggest that simple tools such as work ability should be used more frequently as outcome measures in trials with RA patients.

The metabolic syndrome is amplified in hypothyroid rheumatoid arthritis patients: a cross-sectional study.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of cardiovascular disease (CVD), which is even more pronounced in hypothyroid RA patients. An unfavourable cardiovascular risk profile conferred by a higher prevalence of the metabolic syndrome (MetS) and a higher Framingham risk score might explain this amplified cardiovascular morbidity. This study compared first, MetS (features) and second, the Framingham 10-year CVD risk in RA patients with hypothyroidism compared with euthyroid RA patients. METHODS: RA patients participating in the CARRE investigation were divided into two groups: hypothyroid and euthyroid RA patients. MetS according to the National Cholesterol Education Program Third Adult Treatment Panel criteria and the Framingham risk score was compared between hypothyroid and non-hypothyroid CVD event-free RA patients. RESULTS: In total, 257 RA patients were included: 236 with RA (91.8%) and 21 with hypothyroid RA (8.2%), respectively. The prevalence of the MetS was significantly higher in hypothyroid RA patients (43%) compared with RA patients (20%). Moreover, female hypothyroid RA patients had a higher Framingham risk score compared with euthyroid RA patients. With RA patients as the reference category, the age and gender-adjusted prevalence odds ratio for the MetS was 3.5 (95% CI 1.3 to 9.1) in hypothyroid RA. CONCLUSIONS: Hypothyroid RA patients, particularly female patients, have a more unfavourable cardiovascular risk profile, reflected by an increased prevalence of the MetS and higher Framingham score, than euthyroid RA patients, suggesting a greater need for cardiovascular risk management in these patients to prevent future CVD events.

Rheumatoid arthritis is associated with a high prevalence of hypothyroidism that amplifies its cardiovascular risk.

OBJECTIVE: Rheumatoid arthritis (RA) patients have an increased risk of developing cardiovascular diseases (CVD). Other autoimmune diseases such as hypothyroidism are also associated with an enhanced risk for CVD. Our objective was to determine first, the prevalence of hypothyroid disorders in RA patients, and second, the risk of CVD in RA patients with hypothyroid abnormalities. SUBJECTS: were RA patients who participated in an ongoing prospective cohort study of cardiovascular mortality and morbidity (n = 358) in which hypothyroid abnormalities were assessed. CVD was defined as a verified medical history of coronary, cerebral or peripheral arterial disease. RESULTS: Clinical hypothyroidism was observed in 16 of 236 female RA patients (6.8%), which is significantly higher than in the general population of The Netherlands. Subclinical hypothyroidism was detected in 6 out of 236 RA women (2.5%). In female RA patients, CVD was present in 6 out of 16 (37.5%) of all hypothyroid women. The odds ratio for CVD comparing female hypothyroid RA patients with female euthyroid RA patients was 4.1 (95% CI 1.2-14.3) after adjustment for sex, age, diabetes, smoking (ever), hypertension and statin use. CONCLUSIONS: Clinical hypothyroidism was observed three times more often in female RA patients than females in the general population. In female RA patients, clinical hypothyroidism was associated with a fourfold higher risk of CVD in comparison with euthyroid female RA patients independently of the traditional risk factors.