Bone Mineral Density Response to Long-Term Bisphosphonate Treatment and Discontinuation in a Real-World Clinical Service.

OBJECTIVE: Bisphosphonate treatment does not increase bone mineral density (BMD) in all subjects particularly at the femoral neck (FN). Our aim was to evaluate the relationship between response to oral bisphosphonate (oBP) at the FN and change in BMD following discontinuation. METHODS: Data were collected retrospectively from postmenopausal women on oBP for ≥3 years, attending a real-world metabolic clinic at initiation of oBP, discontinuation, and 1 to 2 years post discontinuation. Improvement in BMD ≥4% in the FN and ≥5% for the lumbar spine (LS) were deemed clinically meaningful and used as least significant change (LSC) values. We divided subjects based on FN BMD response and compared outcomes between responders and non-responders after oBP discontinuation. RESULTS: Of the 213 subjects, 32.1% showed an increase ≥LSC at the FN compared to 57.1% at the LS on treatment (P < .0001). FN responders had lower BMD levels at pretreatment baseline than non-responders both at the FN (0.58 vs 0.62 g/cm2; P = .003) and LS (0.76 vs 0.79 g/cm2; P = .044). Off-treatment, more subjects lost BMD ≥LSC at FN in the responder group than in the non-responder group (37.5% vs 14.2%; P < .001). BMD remained above pre-treatment levels in responders after a median follow-up of 1.52 years. CONCLUSION: BMD response at FN is suboptimal in patients on oBP and is much less common than LS response. FN responders tend to lose the accumulated bone quickly off-treatment, though BMD remains above pretreatment levels. These observations suggest that new approaches may be needed to optimize osteoporosis management in real-world patients.

Progression of subclinical and clinical cardiovascular disease in a UK SLE cohort: the role of classic and SLE-related factors.

OBJECTIVES: We aimed to describe the rate and determinants of carotid plaque progression and the onset of clinical cardiovascular disease (CVD) in a UK SLE cohort. METHODS: Female patients with SLE of white British ancestry were recruited from clinics in the North-West of England and had a baseline clinical and CVD risk assessment including measurement of carotid intima-media thickness (CIMT) and plaque using B-mode Doppler ultrasound. Patients were followed up (>3.5 years after baseline visit) and had a repeat carotid Doppler to assess progression of plaque and CIMT. Clinical CVD events between visits were also noted. RESULTS: Of 200 patients with a baseline scan, 124 (62%) patients had a second assessment at a median (IQR) of 5.8 (5.2-6.3) years follow-up. New plaque developed in 32 (26%) (4.5% per annum) patients and plaque progression was observed in 52 (41%) patients. Factors associated with plaque progression were older age (OR 1.13; 95% CI 1.06 to 1.20), anticardiolipin (OR 3.36; 1.27 to 10.40) and anti-Ro (OR 0.31; 0.11 to 0.86) antibodies. CVD events occurred in 7.2% over 5.8 years compared with 1.0% predicted using the Framingham risk score (p<0.001). Higher triglycerides (OR 3.6; 1.23 to 10.56), cyclophosphamide exposure 'ever' (OR 16.7; 1.46 to 63.5) and baseline Systemic Lupus International Collaborating Clinics damage index score (OR 9.62; 1.46 to 123) independently predicted future CVD events. CONCLUSION: Accelerated atherosclerosis remains a major challenge in SLE disease management. A more comprehensive approach to CVD risk management taking into account disease factors such as severity and anticardiolipin antibody status may be necessary to improve CVD outcomes in this high-risk population.

Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study.

OBJECTIVES: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). METHODS: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). RESULTS: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. CONCLUSION: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.

Comparative clinical utility of once-weekly subcutaneous abatacept in the management of rheumatoid arthritis.

Biologic therapies in rheumatoid arthritis are now part of standard practice for disease that proves difficult to control with conventional disease-modifying anti-rheumatic drugs. While anti-tumor necrosis factor therapies have been commonly used, other targeted biologic therapies with different mechanisms of action are becoming increasingly available. Abatacept is a recombinant fusion protein that inhibits the T-cell costimulatory molecules required for T-cell activation. Intravenous abatacept has good clinical efficacy with an acceptably low toxicity profile in rheumatoid arthritis, but the subcutaneous mode of delivery has only recently become available. In this article, we examine key efficacy and safety data for subcutaneous abatacept in rheumatoid arthritis, incorporating evidence from five large Phase III studies that included people with an inadequate response to methotrexate and an inadequate response to biologic disease-modifying anti-rheumatic drugs. The results demonstrate that subcutaneous abatacept has efficacy and safety comparable with that of intravenous abatacept and adalimumab. In addition, inhibition of radiographic progression at year 1 in relatively early rheumatoid arthritis is consistent with that of adalimumab. Subcutaneous abatacept is well tolerated, with very low rates of discontinuation in both short-term and long-term follow-up.

Tofacitinib for treatment of rheumatoid arthritis.

The management of rheumatoid arthritis has seen a dramatic improvement with the introduction of a range of biological disease modifying anti-rheumatic drugs (DMARDs) in recent years. Nonetheless, a proportion of patients remain resistant or intolerant to multiple conventional and biological DMARDs, so innovative strategies are needed to offer patients new therapeutic options. Tofacitinib is the first of a new class of orally active DMARDs, with immunomodulating effects through inhibition of intracellular Janus kinase (JAK) pathways. It has been recently licensed for treatment of adults with moderate to severe RA in the US, Japan, and Russia. In this review the authors evaluate the efficacy and safety of tofacitinib in RA, focusing predominantly on the phase 3 study data.

Shortened telomere length in patients with systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length. METHODS: Telomere length was measured cross-sectionally in whole blood from SLE patients and age-matched healthy female controls, using real-time quantitative polymerase chain reaction. SLE-related and cardiovascular risk factors were assessed. RESULTS: We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37-59 years) and 49.9 years (IQR 32-60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47-1.57), compared to 1.53 (IQR 0.82-2.29) in controls (P = 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (ß ± SE -0.36 ± 0.16; P = 0.023), and longer telomere length was associated with steroid therapy (0.29 ± 0.14; P = 0.046). We also noted an association of longer telomere length with increasing body mass index (ß ± SE 0.07 ± 0.01; P < 0.0001) and tobacco smoking (0.64 ± 0.26; P = 0.016), as well as with the presence of carotid plaque (0.203 ± 0.177; P = 0.032). CONCLUSION: Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.

Diagnosis and treatment of gout in primary care.

The prevalence of gout increases with age. Up to 7% of men > 65 and 3% of women > 85 have gout. Risk of gout increases significantly with increasing serum uric acid levels. Alcohol consumption and purine-rich foods such as red meat and seafood increase the risk of incident gout significantly. Loop and thiazide diuretics are also associated with increased risk. Gout is frequently associated with the metabolic syndrome. Dehydration, increasing creatinine levels, and surgery are also known to precipitate flares. Acute gout manifests as severe joint pain, of rapid onset, reaching maximal intensity within a few hours. Gout has a predilection for lower extremity joints. It often starts at the first metatarsophalangeal joint, a condition termed podagra. Other common sites of gouty flares include: tarsal and subtalar joints; ankle; knee; wrist; small joints of the hands; Achilles tendon; and olecranon bursae. The joint affected is usually hot, red, swollen and very painful. This is often associated with skin erythema. Identification of MSU crystals in the synovial fluid of an inflamed joint or from tophi allows a definite diagnosis of gout to be made. Hyperuricaemia does not confirm or exclude gout as most people with hyperuricaemia are asymptomatic, while serum uric acid levels tend to decrease during acute attacks. Short-acting NSAIDs should be used at maximal dose as first drug of choice if not contraindicated. In patients at risk of GI complications, co-prescription of a proton pump inhibitor or the use of COX-2 selective agents should be considered. Colchicine can be particularly useful in patients with heart failure in whom NSAIDs are contraindicated but should be avoided in patients with severe renal impairment. Joint aspiration and injection of intra-articular steroids is one of the most effective ways of treating acute monoarthritic gout. Uric acid lowering therapy is initiated if a patient suffers two or more attacks in one year. Many rheumatologists will start this therapy in hyperuricaemic patients whose first attack is very severe or in polyarticular gout.