-
1.
Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial.
Wallace, DJ, Furie, RA, Tanaka, Y, Kalunian, KC, Mosca, M, Petri, MA, Dörner, T, Cardiel, MH, Bruce, IN, Gomez, E, et al
Lancet (London, England). 2018;(10143):222-231
Abstract
BACKGROUND Patients with systemic lupus erythematosus have substantial unmet medical need. Baricitinib is an oral selective Janus kinase (JAK)1 and JAK2 inhibitor that we hypothesised might have therapeutic benefit in patients with systemic lupus erythematosus. METHODS In this double-blind, multicentre, randomised, placebo-controlled, 24-week phase 2 study, patients were recruited from 78 centres in 11 countries. Eligible patients were aged 18 years or older, had a diagnosis of systemic lupus erythematosus, and had active disease involving skin or joints. We randomly assigned patients (1:1:1) to receive once-daily baricitinib 2 mg, baricitinib 4 mg, or placebo for 24 weeks. The primary endpoint was the proportion of patients achieving resolution of arthritis or rash at week 24, as defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K). Efficacy and safety analyses included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02708095. FINDINGS Between March 24, 2016, and April 27, 2017, 314 patients were randomly assigned to receive placebo (n=105), baricitinib 2 mg (n=105), or baricitinib 4 mg (n=104). At week 24, resolution of SLEDAI-2K arthritis or rash was achieved by 70 (67%) of 104 patients receiving baricitinib 4 mg (odds ratio [OR] vs placebo 1·8, 95% CI 1·0-3·3; p=0·0414) and 61 (58%) of 105 patients receiving baricitinib 2 mg (OR 1·3, 0·7-2·3; p=0·39). Adverse events were reported in 68 (65%) patients in the placebo group, 75 (71%) patients in the baricitinib 2 mg group, and 76 (73%) patients in the baricitinib 4 mg group. Serious adverse events were reported in ten (10%) patients receiving baricitinib 4 mg, 11 (10%) receiving baricitinib 2 mg, and five (5%) receiving placebo; no deaths were reported. Serious infections were reported in six (6%) patients with baricitinib 4 mg, two (2%) with baricitinib 2 mg, and one (1%) with placebo. INTERPRETATION The baricitinib 4 mg dose, but not the 2 mg dose, significantly improved the signs and symptoms of active systemic lupus erythematosus in patients who were not adequately controlled despite standard of care therapy, with a safety profile consistent with previous studies of baricitinib. This study provides the foundation for future phase 3 trials of JAK1/2 inhibition with baricitinib as a new potential oral therapy for systemic lupus erythematosus. FUNDING Eli Lilly and Company.
-
2.
Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial.
Pogacnik Murillo, AL, Eckstein, F, Wirth, W, Beavers, D, Loeser, RF, Nicklas, BJ, Mihalko, SL, Miller, GD, Hunter, DJ, Messier, SP
Cells, tissues, organs. 2017;(4):258-266
Abstract
OBJECTIVES The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. METHODS Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. RESULTS The average weight loss amounted to 1.0% in the E group, 10.5% in the D group, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). CONCLUSIONS As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat.
-
3.
The effect of different bearing surfaces on metal ion levels in urine following 28 mm metal-on-metal and 28 mm metal-on-polyethylene total hip arthroplasty.
Tiusanen, H, Mäkelä, K, Kiilunen, M, Sarantsin, P, Sipola, E, Pesola, M
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2013;(3):197-203
Abstract
BACKGROUND AND AIMS Recent advancements in manufacturing technology have enabled more precise tolerances and surface finishes using metal-on-metal bearing surfaces in total hip arthroplasty. The aim of this study was to compare the level of metal ions in urine after implantation of a 28-mm metal-on-metal bearing manufactured from high-carbon wrought alloy and a 28-mm metal-on-polyethylene bearing. MATERIAL AND METHODS A total of 92 total hip arthroplasty patients were prospectively randomized into two groups: those receiving metal-on-metal bearings and those receiving metal-on-polyethylene bearings. Chromium, cobalt, and molybdenum ion levels in urine were measured preoperatively and at 1 year and 2 years postoperatively. RESULTS In the metal-on-polyethylene group, there was a slight increase in mean chromium and cobalt concentrations at 2-year follow-up compared to the preoperative level (p = 0.02 for both chromium and cobalt). In the metal-on-metal group, there was a 15-fold increase in chromium and a 26-fold increase in cobalt at 2-year follow-up compared to the preoperative level (p < 0.001 for both chromium and cobalt). However, the quantity of chromium and cobalt in urine from the metal-on-metal group was not higher at 2-year follow-up than at 1-year follow-up (p = 0.5 and p = 0.6, respectively). CONCLUSIONS The 28-mm metal-on-metal bearings yield chromium and cobalt concentrations in urine that can be higher than those recommended for occupational exposure. However, our results also indicate that a steady state in wear and ion production using metal-on-metal total hip arthroplasty can occur.
-
4.
Effect of intensive lipid-lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease.
Semb, AG, Kvien, TK, DeMicco, DA, Fayyad, R, Wun, CC, LaRosa, JC, Betteridge, J, Pedersen, TR, Holme, I
Arthritis and rheumatism. 2012;(9):2836-46
-
-
Free full text
-
Abstract
OBJECTIVE To examine the effect of intensive lipid-lowering therapy on a composite cardiovascular outcome (cardiovascular disease [CVD]), consisting of mortality and morbidity end points, in patients with inflammatory joint disease (rheumatoid arthritis [RA], ankylosing spondylitis [AS], or psoriatic arthritis [PsA]) by post hoc analysis of 2 prospective trials of statins with a secondary end point of CVD outcome (the Treating to New Targets [TNT] and Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] studies). METHODS Of the 18,889 patients participating in the 2 trials, 199 had RA, 46 had AS, and 35 had PsA. Lipid-lowering therapy consisted of an intensive regimen of atorvastatin 80 mg or a conventional/low-dose regimen of atorvastatin 10 mg or simvastatin 20-40 mg. The median duration of followup was nearly 5 years. Changes in lipid levels were examined by analyses of covariance. The effect on CVD was examined by Cox regression analyses, and heterogeneity tests were performed. RESULTS Patients with RA and those with AS had lower baseline cholesterol levels than patients without inflammatory joint disease (least squares mean ± SEM 180.7 ± 2.3 mg/dl and 176.5 ± 4.7 mg/dl, respectively, versus 185.6 ± 0.2 mg/dl; P = 0.03 and P = 0.05, respectively). Statin treatment led to a comparable decrease in lipid levels and a 20% reduction in overall risk of CVD in both patients with and those without inflammatory joint disease. CONCLUSION Our findings indicate that patients with and those without inflammatory joint disease experience comparable lipid-lowering effects and CVD risk reduction after intensive treatment with statins.
-
5.
A feasibility study of valerian extract for sleep disturbance in person with arthritis.
Taibi, DM, Bourguignon, C, Gill Taylor, A
Biological research for nursing. 2009;(4):409-17
Abstract
OBJECTIVES To present a pilot study of valerian to explore issues of feasibility and efficacy in studies of sedative herbs for arthritis-related sleep disturbance. METHODS Fifteen persons with arthritis and mild sleep disturbance were randomized to receive 600 mg valerian (Valeriana officinalis, n = 7) or placebo (n = 8) for five nights. RESULTS Protocol adherence (dosing and data collection) was high. Allocation concealment was successful using a novel approach for matching the placebo on the distinctive odor of valerian. Nonsignificant differences between the groups were found on all sleep outcomes, measured by daily diaries and wrist actigraphy. CONCLUSION The study methods were feasible, except for recruitment issues (addressed in the discussion), and may guide the testing of other sedative herbs for persons with arthritis. Although efficacy outcomes were inconclusive due to the small sample size of this study, recent evidence from larger trials of valerian also does not support its efficacy.
-
6.
Effects of 4-year treatment with once-weekly clodronate on prevention of corticosteroid-induced bone loss and fractures in patients with arthritis: evaluation with dual-energy X-ray absorptiometry and quantitative ultrasound.
Frediani, B, Falsetti, P, Baldi, F, Acciai, C, Filippou, G, Marcolongo, R
Bone. 2003;(4):575-81
Abstract
The aim of this placebo-controlled study was to determine whether once-weekly clodronate could prevent osteoporosis in patients with arthritis at the start of corticosteroid therapy. One hundred sixty-three patients, 18 to 90 years of age, with rheumatoid or psoriatic arthritis, were randomly assigned to receive either clodronate (100 mg im/week) plus calcium and vitamin D (1000 mg and 800 UI, respectively) or calcium and vitamin D alone. Patients had started therapy with prednisone or its equivalent within the previous 100 days and had bone mineral density <2.5 SD below mean young normal values at the lumbar spine or femoral neck. The primary outcome was the difference between the two treatment groups at months 12, 24, 36, and 48 in the mean percentage change from baseline in the bone mineral density of the lumbar spine, femur (neck and total), and total body. Secondary measurements included changes in the stiffness index evaluated by ultrasound measurements and the rate of new vertebral fractures. The bone density and stiffness did not change significantly in the clodronate plus calcium and vitamin D group, whereas it declined significantly in the calcium plus vitamin D group. The difference between treatment groups at 48 months in the mean change from baseline was 8.78 +/- 1.4% for the lumbar spine (P < 0.01), 7.31 +/- 1.12% for the femoral neck (P < 0.01), 7.92 +/- 1.93% for the trochanter (P < 0.01), 8.39 +/- 1.80% for total femur (P < 0.01), 6.94 +/- 1.09% for total body (P < 0.01), and 9.38 +/- 2.21% for stiffness of os calcis (P < 0.01). Depending on the skeletal regions evaluated, 85 to 98% of patients treated with clodronate had a densitometric change lower than the lowest significant densitometric difference. One hundred percent of patients treated with calcium plus vitamin D had a densitometric decrease greater than the lowest significant difference. The relative risk of vertebral fractures and multiple vertebral fractures in the clodronate group compared to the calcium plus vitamin D group was 0.63 (0.35-0.98, 95% CI) and 0.25 (0.15-0.91, 95% CI), respectively. We concluded that pulsatory administration of im clodronate once weekly is a safe therapy for preventing corticosteroid induced osteoporosis in patients with arthritis.
-
7.
A randomized controlled study of the Arthritis Self-Management Programme in the UK.
Barlow, JH, Turner, AP, Wright, CC
Health education research. 2000;(6):665-80
Abstract
The objective of this study was to determine whether the Arthritis Self-Management Programme (ASMP) improves perceptions of control, health behaviours and health status, and changes use of health care resources. The design was a pragmatic randomized controlled study; participants were allocated to ASMP (Intervention Group) or a 4-month waiting-list Control Group. The Intervention Group completed a 12-month follow-up. In total, 544 people with arthritis were recruited from the community--311 in the Intervention Group and 233 in the Control Group. Main outcome measures included: arthritis self-efficacy, health behaviours (exercise, cognitive symptom management, diet and relaxation) and health status (pain, fatigue, anxiety, depression and positive affect). At 4 months follow-up, the ASMP had a significant effect on arthritis self-efficacy for other symptoms and pain subscales. Performance of a range of health behaviours (cognitive symptom management, communication with physicians, dietary habit, exercise and relaxation) was significantly greater among the Intervention Group. The Intervention Group were significantly less depressed and had greater positive mood. In addition, trends towards decreases on fatigue and anxiety were noted. Physical functioning, pain and GP visits remained stable at 4 months. A similar pattern of findings was found at 12 months follow-up for the Intervention Group. Furthermore, a significant improvement was found on pain and visits to GPs had decreased. Apart from a small improvement on physical functioning among the Intervention Group participants with osteoarthritis 12 months, all effects were independent of the type of arthritis. The findings suggest that the ASMP is effective in promoting improvements in perception of control, health behaviours and health status, when delivered in UK settings.