Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM.

OBJECTIVES: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. METHODS: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. RESULTS: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. CONCLUSIONS: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM).

OBJECTIVES: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target. METHODS: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models. RESULTS: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52). CONCLUSION: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

Testing population-based performance measures identifies gaps in juvenile idiopathic arthritis (JIA) care.

BACKGROUND: The study evaluates Performance Measures (PMs) for Juvenile Idiopathic Arthritis (JIA): The percentage of patients with new onset JIA with at least one visit to a pediatric rheumatologist in the first year of diagnosis (PM1); and the percentage of patients with JIA under rheumatology care seen in follow-up at least once per year (PM2). METHODS: Validated JIA case ascertainment algorithms were used to identify cases from provincial health administrative databases in Manitoba, Canada in patients < 16 years between 01/04/2005 and 31/03/2015. PM1: Using a 3-year washout period, the percentage of incident JIA patients with ≥1 visit to a pediatric rheumatologist in the first year was calculated. For each fiscal year, the proportion of patients expected to be seen in follow-up who had a visit were calculated (PM2). The proportion of patients with gaps in care of > 12 and > 14 months between consecutive visits were also calculated. RESULTS: One hundred ninety-four incident JIA cases were diagnosed between 01/04/2008 and 03/31/2015. The median age at diagnosis was 9.1 years and 71% were female. PM1: Across the years, 51-81% of JIA cases saw a pediatric rheumatologist within 1 year. PM2: Between 58 and 78% of patients were seen in yearly follow-up. Gaps > 12, and > 14, months were observed once during follow-up in 52, and 34%, of cases, and ≥ twice in 11, and 5%, respectively. CONCLUSIONS: Suboptimal access to pediatric rheumatologist care was observed which could lead to diagnostic and treatment delays and lack of consistent follow-up, potentially negatively impacting patient outcomes.

Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.

BACKGROUND: Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice. OBJECTIVES: To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures. SEARCH METHODS: We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Four placebo-controlled trials were at low risk of bias and one was possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.7 points better (0.3 better to 1.2 better) with vertebroplasty, an absolute pain reduction of 7% (3% better to 12% better, minimal clinical important difference is 15%) and relative reduction of 10% (4% better to 17% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.5 points better (0.4 better to 2.6 better) in the vertebroplasty group, absolute improvement 7% (2% to 11% better), relative improvement 9% better (2% to 15% better) (four trials, 472 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.3 points better (1.4 points worse to 6.7 points better), an absolute imrovement of 2% (1% worse to 6% better); relative improvement 4% better (2% worse to 10% better) (three trials, 351 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Low-quality evidence (downgraded due to imprecision and potential for bias from the usual-care controlled trials) indicates uncertainty around the risk estimates of harms with vertebroplasty. The incidence of new symptomatic vertebral fractures (from six trials) was 48/418 (95 per 1000; range 34 to 264)) in the vertebroplasty group compared with 31/422 (73 per 1000) in the control group; RR 1.29 (95% CI 0.46 to 3.62)). The incidence of other serious adverse events (five trials) was 16/408 (34 per 1000, range 18 to 62) in the vertebroplasty group compared with 23/413 (56 per 1000) in the control group; RR 0.61 (95% CI 0.33 to 1.10). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain (acute versus subacute). Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity. AUTHORS' CONCLUSIONS: We found high- to moderate-quality evidence that vertebroplasty has no important benefit in terms of pain, disability, quality of life or treatment success in the treatment of acute or subacute osteoporotic vertebral fractures in routine practice when compared with a sham procedure. Results were consistent across the studies irrespective of the average duration of pain.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.

Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.

BACKGROUND: Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice. OBJECTIVES: To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures. SEARCH METHODS: We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Three placebo-controlled trials were at low risk of bias and two were possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials (one with incomplete data reported) indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.6 points better (0.2 better to 1 better) with vertebroplasty, an absolute pain reduction of 6% (2% better to 10% better, minimal clinical important difference is 15%) and relative reduction of 9% (3% better to14% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.7 points better (0.3 better to 3.1 better) in the vertebroplasty group, absolute improvement 7% (1% to 14% better), relative improvement 10% better (3% to 18% better) (three trials, 296 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.75 points (3.53 worse to 9.02 better) in the vertebroplasty group, absolute change: 3% better (4% worse to 9% better), relative change: 5% better (6% worse to 15% better (two trials, 175 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Moderate-quality evidence (low number of events) from seven trials (four placebo, three usual care, 1020 participants), up to 24 months follow-up, indicates we are uncertain whether vertebroplasty increases the risk of new symptomatic vertebral fractures (70/509 (or 130 per 1000; range 60 to 247) observed in the vertebroplasty group compared with 59/511 (120 per 1000) in the control group; RR 1.08 (95% CI 0.62 to 1.87)).Similarly, moderate-quality evidence (low number of events) from five trials (three placebo, two usual care, 821 participants), indicates uncertainty around the risk of other serious adverse events (18/408 or 76 per 1000, range 6 to 156) in the vertebroplasty group compared with 26/413 (or 106 per 1000) in the control group; RR 0.64 (95% CI 0.36 to 1.12). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity. AUTHORS' CONCLUSIONS: Based upon high- to moderate-quality evidence, our updated review does not support a role for vertebroplasty for treating acute or subacute osteoporotic vertebral fractures in routine practice. We found no demonstrable clinically important benefits compared with placebo (sham procedure) and subgroup analyses indicated that the results did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.

Bisphosphonates for steroid-induced osteoporosis.

BACKGROUND: This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. OBJECTIVES: To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase up to April 2016 and International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for relevant articles and conference proceedings with no language restrictions. We searched two clinical trial registries for ongoing and recently completed studies (ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed reference lists of relevant review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) satisfying the following criteria: 1) prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0 mg/day or more; 3) active treatment including bisphosphonates of any type alone or in combination with calcium or vitamin D; 4) comparator treatment including a control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting relevant outcomes. We excluded trials that included people with transplant-associated steroid use. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, performed 'risk of bias' assessment and evaluated the certainty of evidence using the GRADE approach. Major outcomes of interest were the incidence of vertebral and nonvertebral fractures after 12 to 24 months; the change in bone mineral density (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse events; withdrawals due to adverse events; and quality of life. We used standard Cochrane methodological procedures. MAIN RESULTS: We included a total of 27 RCTs with 3075 participants in the review. Pooled analysis for incident vertebral fractures included 12 trials (1343 participants) with high-certainty evidence and low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new vertebral fractures in the control group compared with 31/746 (or 44 per 1000; range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to 65% better) with bisphosphonates; absolute increased benefit of 2% fewer people sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that approximately 31 people would need to be treated with bisphosphonates to prevent new vertebral fractures in one person.Pooled analysis for incident nonvertebral fractures included nine trials with 1245 participants with low-certainty evidence (downgraded for imprecision and serious risk of bias as a patient-reported outcome). In this analysis 30/546 (or 55 per 1000) people experienced new nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000; range 25 to 69) in the bisphosphonate group; relative improvement of 21% with bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer people with fractures with bisphosphonates (4% fewer to 1% more).Pooled analysis on BMD change at the lumbar spine after 12 months included 23 trials with 2042 patients. Eighteen trials with 1665 participants were included in the pooled analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes was moderate-certainty (downgraded for indirectness as a surrogate marker for osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported stabilisation or increase in BMD, while the control groups showed decreased BMD over the study period. At the lumbar spine, there was an absolute increase in BMD of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group compared to the control group (1.45% to 2.68% higher) with a relative improvement of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7).Pooled analysis on serious adverse events included 15 trials (1703 participants) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162 per 1000) people experienced serious adverse events in the control group compared to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group; absolute increased harm of 0% more serious adverse events (2% fewer to 2% more); a relative per cent change with 9% improvement (12% worse to 26% better).Pooled analysis for withdrawals due to adverse events included 15 trials (1790 patients) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 63/866 (or 73 per 1000) people withdrew in the control group compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group; an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1% fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23% better).Quality of life was not assessed in any of the trials. AUTHORS' CONCLUSIONS: There was high-certainty evidence that bisphosphonates are beneficial in reducing the risk of vertebral fractures with data extending to 24 months of use. There was low-certainty evidence that bisphosphonates may make little or no difference in preventing nonvertebral fractures. There was moderate-certainty evidence that bisphosphonates are beneficial in preventing and treating corticosteroid-induced bone loss at both the lumbar spine and femoral neck. Regarding harm, there was low-certainty evidence that bisphosphonates may make little or no difference in the occurrence of serious adverse events or withdrawals due to adverse events. We are cautious in interpreting these data as markers for harm and tolerability due to the potential for bias.Overall, our review supports the use of bisphosphonates to reduce the risk of vertebral fractures and the prevention and treatment of steroid-induced bone loss.

Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.

BACKGROUND: Percutaneous vertebroplasty is widely used to treat acute and subacute painful osteoporotic vertebral fractures although recent placebo-controlled trials have questioned its value. OBJECTIVES: To synthesise the available evidence regarding the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures. SEARCH METHODS: We searched CENTRAL, MEDLINE and EMBASE up to November 2014. We also reviewed reference lists of review articles, trials and trial registries to identify any other potentially relevant trials. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) including adults with painful osteoporotic vertebral fractures of any duration and comparing vertebroplasty with placebo (sham), usual care, or any other intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, performed 'Risk of bias' assessment and assessed the quality of the body of evidence for the main outcomes using GRADE. MAIN RESULTS: Eleven RCTs and one quasi-RCT conducted in various countries were included. Two trials compared vertebroplasty with placebo (209 randomised participants), six compared vertebroplasty with usual care (566 randomised participants) and four compared vertebroplasty with kyphoplasty (545 randomised participants). Trial size varied from 34 to 404 participants, most participants were female, mean age ranged between 63.3 and 80 years, and mean symptom duration varied from a week to more than six months.Both placebo-controlled trials were judged to be at low overall risk of bias while other included trials were generally considered to be at high risk of bias across a range of criteria, most seriously due to lack of participant and study personnel blinding.Compared with placebo, there was moderate quality evidence based upon two trials that vertebroplasty provides no demonstrable benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success. At one month, mean pain (on a scale 0 to 10, higher scores indicate more pain) was 5 points with placebo and 0.7 points better (1.5 better to 0.15 worse) with vertebroplasty, an absolute pain reduction of 7% (15% better to 1.5% worse) and relative reduction of 10% (21% better to 2% worse) (two trials, 201 participants). At one month, mean disability measured by the Roland Morris Disability Questionnaire (scale range 0 to 23, higher scores indicate worse disability) was 13.6 points in the placebo group and 1.1 points better (2.9 better to 0.8 worse) in the vertebroplasty group, absolute improvement in disability 4.8% (12.8% better to 3.3% worse), relative change 6.3% better (17.0% better to 4.4% worse) (two trials, 201 participants).At one month, disease-specific quality of life measured by the QUALEFFO (scale 0 to 100, higher scores indicating worse quality of life) was 2.4 points in the placebo group and 0.40 points worse (4.58 better to 5.38 worse) in the vertebroplasty group, absolute change: 0.4% worse (5% worse to 5% better), relative change 0.7% worse (9% worse to 8% better (based upon one trial, 73 participants). At one month overall quality of life measured by the EQ5D (0 = death to 1 = perfect health, higher scores indicate greater quality of life at one month was 0.27 points in the placebo group and 0.05 points better (0.01 worse to 0.11 better) in the vertebroplasty group, absolute improvement in quality of life 5% (1% worse to 11% better), relative change 18% better (4% worse to 39% better) (two trials, 201 participants). Based upon one trial (78 participants) at one month, 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; range 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute risk difference 9% more reported success (11% fewer to 29% more); relative change 40% more reported success (33% fewer to 195% more).Based upon moderate quality evidence from three trials (one placebo, two usual care, 281 participants) with up to 12 months follow-up, we are uncertain whether or not vertebroplasty increases the risk of new symptomatic vertebral fractures (28/143 observed in the vertebroplasty group compared with 19/138 in the control group; RR 1.47 (95% CI 0.39 to 5.50).Similary, based upon moderate quality evidence from two placebo-controlled trials (209 participants), we are uncertain about the exact risk of other adverse events (3/106 were observed in the vertebroplasty group compared with 3/103 in the placebo group; RR 1.01 (95% CI 0.21 to 4.85)). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses provided limited evidence that the effects did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Including data from the six trials that compared vertebroplasty with usual care in a sensitivity analyses inconsistently altered the primary results, with all combined analyses displaying substantial to considerable heterogeneity. AUTHORS' CONCLUSIONS: Based upon moderate quality evidence, our review does not support a role for vertebroplasty for treating osteoporotic vertebral fractures in routine practice. We found no demonstrable clinically important benefits compared with a sham procedure and subgroup analyses indicated that results did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the lack of high quality evidence supporting benefit of vertebroplasty and its potential for harm.

Discordant indigenous and provider frames explain challenges in improving access to arthritis care: a qualitative study using constructivist grounded theory.

INTRODUCTION: Access to health services is a determinant of population health and is known to be reduced for a variety of specialist services for Indigenous populations in Canada. With arthritis being the most common chronic condition experienced by Indigenous populations and causing high levels of disability, it is critical to resolve access disparities through an understanding of barriers and facilitators to care. The objective of this study was to inform future health services reform by investigating health care access from the perspective of Aboriginal people with arthritis and health professionals. METHODS: Using constructivist grounded theory methodology we investigated Indigenous peoples' experiences in accessing arthritis care through the reports of 16 patients and 15 healthcare providers in Alberta, Canada. Semi-structured interviews were conducted between July 2012 and February 2013 and transcribed verbatim. The patient and provider data were first analyzed separately by two team members then brought together to form a framework. The framework was refined through further analysis following the multidisciplinary research team's discussions. Once the framework was developed, reports on the patient and provider data were shared with each participant group independently and participants were interviewed to assess validity of the summary. RESULTS: In the resulting theoretical framework Indigenous participants framed their experience with arthritis as 'toughing it out' and spoke of racism encountered in the healthcare setting as a deterrent to pursuing care. Healthcare providers were frustrated by high disease severity and missed appointments, and framed Indigenous patients as lacking 'buy-in'. Constraints imposed by complex healthcare systems contributed to tensions between Indigenous peoples and providers. CONCLUSION: Low specialist care utilization rates among Indigenous people cannot be attributed to cultural and social preferences. Further, the assumptions made by providers lead to stereotyping and racism and reinforce rejection of healthcare by patients. Examples of 'working around' the system were revealed and showed potential for improved utilization of specialist services. This framework has significant implications for health policy and indicates that culturally safe services are a priority in addressing chronic disease management.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

OBJECTIVE: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. METHODS: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. RESULTS: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [ß(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later. CONCLUSION: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.

Healthcare service utilisation costs are reduced when rheumatoid arthritis patients achieve sustained remission.

OBJECTIVE: Determine healthcare service utilisation costs among patients using biological therapies for rheumatoid arthritis (RA), considering the magnitude and duration of patient response achieved. METHODS: Clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm) was linked with provincial physician billing claims, outpatient visits and hospitalisations. The annual mean healthcare service utilisation costs (total, RA-attributable, non-RA attributable) were estimated for patients during the best disease activity level reached during treatment. RESULTS: Of 1086 patients: 16% achieved DAS28 remission >1 year, 37% had a DAS28 remission period <1 year, 13% had a low disease activity (LDA) period <1 year and 31% had persistent moderate or high disease activity. Mean annual healthcare service utilisation cost savings for those in sustained remission was $2391 (95% CI 1437 to 3909, p<0.001) and $2104 (95% CI 838 to 3512, p<0.001) for those with non-sustained LDA, relative to the persistent disease activity group. Savings were also observed for those in sustained remission compared to non-sustained remission (annual savings $1422, 95% CI 564 to 2796, p<0.001). RA-related costs were consistent across disease activity and cost categories; the majority of costs were attributable to non-RA related hospitalisations. CONCLUSIONS: We provide evidence of economic benefits to the healthcare system when RA patients achieve persistent good disease control. Benefits from brief periods of remission and LDA are also observed. Coupled with an expected increase in productivity from improved disease control, there is societal benefit to the utilisation of biologics in RA management to achieve treatment goals.

The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study.

BACKGROUND: Oral bisphosphonates are commonly used to prevent / treat osteoporosis. However, bisphosphonate treatment is not without risk and serious adverse effects, including upper gastrointestinal bleeding (UGIB) have been described. We sought to determine if new users of bisphosphonate drugs were more likely to suffer a serious UGIB within 120 days of drug initiation. METHODS: This was a population-based nested cohort study utilizing administrative healthcare data in British Columbia, Canada. Community based individuals ≥ 65 years with a new prescription for a bisphosphonate between 1991 and 2007 were included. A multivariate logistic regression model was used to examine the relationship between older age and the development of a serious UGIB within 120 days of new exposure to oral bisphosphonate drugs. RESULTS: Within the exposure cohort (n = 26,223), 117 individuals had suffered a serious UGIB within 120 days of incident bisphosphonate use. Cases tended to be > 80 years old, and were significantly more likely to have had a past history of gastric ulcer disease, a remote history of serious UGIB, and had been dispensed proton pump inhibitor (PPI) medications (p < 0.001 for all comparisons). After adjustment for confounding covariates, those > 80 years were more than twice as likely to suffer a UGIB when compared to those ≤ 80 years (adjusted OR = 2.03; 95% CI 1.40-2.94). A past history of serious UGIB was the strongest predictor of UGIB within 120 days of incident bisphosphonate use (adjusted OR = 2.28; 95% CI = 1.29-4.03) followed by PPI use (adjusted OR = 2.04; 95% CI = 1.35-3.07). Males were 70% more likely to suffer an UGIB compared to females (adjusted OR = 1.69; 95% CI = 1.05-2.72). CONCLUSIONS: Upper GIB is a rare, but serious, side effect of bisphosphonate therapy more often afflicting older individuals. At the same time, concern about potential rare adverse events should not discourage clinicians from prescribing bisphosphonate drugs, particularly in older patients who have already sustained a fragility fracture. Clinicians must remain cognizant of potential adverse events associated with bisphosphonate use and should routinely ask about pre-existing GI disorders and concurrent medication history prior to prescribing these drugs.

Development and testing of the rheumatoid arthritis quality of care survey.

OBJECTIVES: The Rheumatoid Arthritis (RA) Quality of Care Survey (RAQCS) was developed to measure care quality according to a previously developed national RA quality improvement framework. METHODS: The development of the RAQCS occurred over 3 phases. First, the survey was developed by a team of healthcare providers, researchers, and two patient partners based on the existing national quality framework's 21 performance measures (PMs) and strategic objectives. Second, cognitive debriefing interviews were conducted with individuals living with RA to identify survey clarity, appropriateness of survey questions, and response options. Third, the survey was revised and distributed to participants recruited from Rheum4U (rheumatology longitudinal cohort). Results were tabulated and compared with a chart audit of participant medical records. RESULTS: Fifty-three participants completed the RAQCS. High performance (i.e., ≥70% meeting PM) was observed for 13 of 20 PMs. Lower performance was seen for the remaining PMs, which included documentation of body mass index (BMI) and smoking status, discussion of physical activity goals, comorbidity management including risk assessments for cardiovascular health and fragility fractures and disease activity assessment. There was high agreement (≥70%) between the RAQCS and chart review for 9 of 20 PMs. CONCLUSIONS: High agreement was observed between the RAQCS and chart review for selected PMs. The RAQCS may also be a valuable tool for quality improvement for measures where data are not usually available through other sources. Further testing of the RAQCS is needed to ascertain its reliability and validity as a patient self-reported tool to measure RA care quality.

Geographic Variation in the Prevalence of Rheumatoid Arthritis in Alberta, Canada.

OBJECTIVES: Timely access to rheumatologists remains a challenge in Alberta, a Canadian province with vast rural areas, whereas rheumatologists are primarily clustered in metro areas. To address the goal of timely and equitable access to rheumatoid arthritis (RA) care, health planners require information at the regional and local level to determine the RA prevalence and the associated health care needs. METHODS: Using Alberta Health administrative databases, we identified RA-prevalent cases (April 1, 2015-March 31, 2016) on the basis of a validated case definition. Age- and sex-standardized prevalence rates per 1000 population members and the standardized rates ratio (SRR) were calculated. We applied Global Moran's I and Gi* hotspot analysis using three different weight matrices to explore the geospatial pattern of RA prevalence in Alberta. RESULTS: Among 38 350 RA cases (68% female; n = 26 236), the prevalence rate was 11.81 cases per 1000 population members (95% confidence interval [CI] 11.80-11.81) after age and sex standardization. Approximately 60% of RA cases resided in metro (Calgary and Edmonton) and moderate metro areas. The highest rate was observed in rural areas (14.46; 95% CI 14.45-14.47; SRR 1.28), compared with the lowest in metro areas (10.69; 95% CI 10.68-10.69; SRR 0.82). The RA prevalence across local geographic areas ranged from 4.7 to 30.6 cases. The Global Moran's I index was 0.15 using three different matrices (z-score 3.96-4.24). We identified 10 hotspots in the south and north rural areas and 18 cold spots in metro and moderate metro Calgary. CONCLUSION: The findings highlight notable rural-urban variation in RA prevalence in Alberta. Our findings can inform strategies aimed at reducing geographic disparities by targeting areas with high health care needs.

A Population-Based Approach to Reporting System-Level Performance Measures for Rheumatoid Arthritis Care.

OBJECTIVE: To operationalize and report on nationally endorsed rheumatoid arthritis (RA) performance measures (PMs) using health administrative data for British Columbia (BC), Canada. METHODS: All patients with RA in BC ages ≥18 years were identified between January 1, 1997 and December 31, 2009 using health administrative data and followed until December 2014. PMs tested include: the percentage of incident patients with ≥1 rheumatologist visit within 365 days; the percentage of prevalent patients with ≥1 rheumatologist visit per year; the percentage of prevalent patients dispensed disease-modifying antirheumatic drug (DMARD) therapy; and time from RA diagnosis to DMARD therapy. Measures were reported on patients seen by rheumatologists, and in the total population. RESULTS: The cohort included 38,673 incident and 57,922 prevalent RA cases. The percentage of patients seen by a rheumatologist within 365 days increased over time (35% in 2000 to 65% in 2009), while the percentage of RA patients under the care of a rheumatologist seen yearly declined (79% in 2001 to 39% in 2014). The decline was due to decreasing visit rates with increasing follow-up time rather than calendar effect. The percentage of RA patients dispensed a DMARD was suboptimal over follow-up (37% in 2014) in the total population but higher (87%) in those under current rheumatologist care. The median time to DMARD in those seen by a rheumatologist improved from 49 days in 2000 to 23 days in 2009, with 34% receiving treatment within the 14-day benchmark. CONCLUSION: This study describes the operationalization and reporting of national PMs using administrative data and identifies gaps in care to further examine and address.

Strategies for developing and implementing a rheumatoid arthritis healthcare quality framework: a thematic analysis of perspectives from arthritis stakeholders.

OBJECTIVES: To obtain stakeholder perspectives to inform the development and implementation of a rheumatoid arthritis (RA) healthcare quality measurement framework. DESIGN: Qualitative study using thematic analysis of focus groups and interviews. SETTING: Arthritis stakeholders from across Canada including healthcare providers, persons living with RA, clinic managers and policy leaders were recruited for the focus groups and interviews. PARTICIPANTS: Fifty-four stakeholders from nine provinces. INTERVENTIONS: Qualitative researchers led each focus group/interview using a semistructured guide; the digitally recorded data were transcribed verbatim. Two teams of two coders independently analysed the transcripts using thematic analysis. RESULTS: Perspectives on the use of different types of measurement frameworks in healthcare were obtained. In particular, stakeholders advocated for the use of existing healthcare frameworks over frameworks developed in the business world and adapted for healthcare. Persons living with RA were less familiar with specific measurement frameworks, however, they had used existing online public forums for rating their experience and quality of healthcare provided. They viewed a standardised framework as potentially useful for assisting with monitoring the care provided to them individually. Nine guiding principles for framework development and 13 measurement themes were identified. Perceived barriers identified included access to data and concerns about how measures in the framework were developed and used. Effective approaches to framework implementation included having sound knowledge translation strategies and involving stakeholders throughout the measurement development and reporting process. Clinical models of care and health policies conducive to outcome measurement were highlighted as drivers of successful measurement initiatives. CONCLUSION: These important perspectives will be used to inform a healthcare quality measurement framework for RA.

Development of a Patient-centered Quality Measurement Framework for Measuring, Monitoring, and Optimizing Rheumatoid Arthritis Care in Canada.

OBJECTIVE: The aim of this study was to develop a patient-centered quality measurement framework to address a predefined vision statement and 7 strategic objectives for rheumatoid arthritis (RA) care that was developed in prior qualitative work with arthritis stakeholders. METHODS: One hundred forty-seven RA-related performance measures (PMs) were identified from a systematic review. A candidate list of 26 PMs meeting predefined criteria and addressing the strategic objectives previously defined was then assessed during a 3-round (R) modified Delphi. Seventeen panelists with expertise in RA, quality measurement, and/or lived experience with RA rated each PM on a 1-9 scale based on the items of importance, feasibility, and priority for inclusion in the framework during R1 and R3, with a moderated discussion in R2. PMs with median scores ≥ 7 on all 3 items without disagreement were included in the final set, which then underwent public comment. RESULTS: Twenty-one measures were included in the final framework (15 PMs from the Delphi and 6 published system-level measures on access to care and treatment). The measures included 4 addressing early access to care and timely diagnosis, 12 evidence-based care for RA and related comorbidities, 1 addressing patient participation as an informed partner in care, and 4 on patient outcomes. CONCLUSION: The proposed framework builds upon existing measures capturing early access to care and treatment in RA and adds important PMs to promote high-quality RA care and outcome measurement. In the next phase, the authors will test the framework in clinical practice in addition to addressing certain areas where no suitable PMs were identified.

Evaluating Quality of Care for Rheumatoid Arthritis for the Population of Alberta Using System-level Performance Measures.

OBJECTIVE: We evaluated 4 national rheumatoid arthritis (RA) system-level performance measures (PM) in Alberta, Canada. METHODS: Incident and prevalent RA cases ≥ 16 years of age since 2002 were identified using a validated case definition applied in provincial administrative data. Performance was ascertained through analysis of health data between fiscal years 2012/13-2015/16. Measures evaluated were as follows: proportion of incident RA cases with a rheumatologist visit within 1 year of first RA diagnosis code (PM1); proportion of prevalent RA patients who were dispensed a disease-modifying antirheumatic drug (DMARD) annually (PM2); time from first visit with an RA code to DMARD dispensation and proportion of incident cases where the 14-day benchmark for dispensation was met (PM3); and proportion of patients seen in annual follow-up (PM4). RESULTS: There were 31,566 prevalent and 2730 incident RA cases (2012/13). Over the analysis period, the proportion of patients seen by a rheumatologist within 1 year of onset (PM1) increased from 55% to 63%; however, the proportion of RA patients dispensed DMARD annually (PM2) remained low at 43%. While the median time to DMARD from first visit date in people who received DMARD improved over time from 39 days to 28 days, only 38-41% of patients received treatment within the 14-day benchmark (PM3). The percentage of patients seen in yearly follow-up (PM4) varied between 73-80%. CONCLUSION: The existing Alberta healthcare system for RA is suboptimal, indicating barriers to accessing specialty care and treatment. Our results inform quality improvement initiatives required within the province to meet national standards of care.

Priorities for High-quality Care in Rheumatoid Arthritis: Results of Patient, Health Professional, and Policy Maker Perspectives.

OBJECTIVE: To elucidate the essential elements of high-quality rheumatoid arthritis (RA) care in order to develop a vision statement and a set of strategic objectives for a national RA quality framework. METHODS: Focus groups and interviews were conducted by experienced qualitative researchers using a semistructured interview or focus group guide with healthcare professionals, patients, clinic managers, healthcare leaders, and policy makers to obtain their perspectives on elements essential to RA care. Purposive sampling provided representation of stakeholder types and regions. Recorded data was transcribed verbatim. Two teams of 2 coders independently analyzed the deidentified transcripts using thematic analysis. Strategic objectives and the vision statement were drafted based on the overarching themes from the qualitative analysis and finalized by a working group. RESULTS: A total of 54 stakeholders from 9 Canadian provinces participated in the project (3 focus groups and 19 interviews). Seven strategic objectives were derived from the qualitative analysis representing the following themes: (1) early access and timeliness of care; (2) evidence-informed, high-quality care for the ongoing management of RA and comorbidities; (3) availability of patient self-management tools and educational materials for shared decision making; (4) multidisciplinary care; (5) patient outcomes; (6) patient experience and satisfaction with care; and (7) equity, the last of which emerged as an overarching theme. The ultimate vision obtained was "ensuring patient-centered, high-quality care for people living with rheumatoid arthritis." CONCLUSION: The 7 strategic objectives that were identified highlight priorities for RA quality of care to be used in developing the National RA Quality Measurement Framework.

Determination of Rheumatoid Arthritis Incidence and Prevalence in Alberta Using Administrative Health Data.

OBJECTIVE: The objective of the study was to estimate the incidence and prevalence of rheumatoid arthritis (RA) in Alberta using administrative health data. METHODS: We identified RA cases in patients 16 years and older by applying a national case definition to linked administrative health data (ie, hospital discharge abstract records, physician claims, and health insurance registry records) using a unique personal identifier. Incidence and prevalence are reported for the 2015-2016 fiscal year and a trend analysis from 2011-2012 to 2015-2016. Incidence and prevalence estimates were standardized using the 2011 Canadian census population. RESULTS: In 2015-2016, the overall crude incidence was 0.74 [95% confidence interval (CI): 0.71-0.77] per 1000 and crude prevalence was 1.08% (95% CI: 1.07-1.09). The women-to-men crude incidence and prevalence sex ratios were 2.04 and 2.19, respectively. People aged 65 to 79 years had the highest incidence of RA, and the highest prevalence was observed among those 80 years and older. From 2011-2012 to 2015-2016, the overall age-standardized incidence decreased [0.97 (95% CI: 0.94-1.01) to 0.79 (95% CI: 0.76-0.82) per 1000], whereas age-standardized prevalence remained constant [1.17 (95% CI: 1.15-1.18) to 1.18 (95% CI: 1.17-1.19)]. CONCLUSION: In Alberta, there was a decreasing trend in RA incidence over the study period, whereas prevalence was stable. These estimates, combined with clinical data, will be used to measure system performance for quality improvement and to inform simulation modeling for planning the expected demand for health services for patients living with RA.

Models of Arthritis Care: A Systems-level Evaluation of Acceptability as a Dimension of Quality of Care.

OBJECTIVE: To describe a systems-level baseline evaluation of central intake (CI) and triage systems in arthritis care within Alberta, Canada. The specific objectives were to (1) describe a process for systems evaluation for the provision of arthritis care; (2) report the findings of the evaluation for different clinical sites that provide arthritis care; and (3) identify opportunities for improving appropriate and timely access based on the findings of the evaluation. METHODS: The study used a convergent mixed methods design. Surveys and semistructured interviews were the main data collection methods. Participants were recruited through 2 rheumatology clinics and 1 hip and knee clinic providing CI and triage, and included patients, referring physicians, specialists, and clinic staff who experienced CI processes. RESULTS: A total of 237 surveys were completed by patients (n = 169), referring physicians (n = 50), and specialists (n = 18). Interviews (n = 25) with care providers and patients provided insights to the survey data. Over 95% of referring physicians agreed that the current process of CI was satisfactory. Referring physicians and specialists reported issues with the referral process and perceived support in care for wait-listed patients. Patients reported positive experiences with access and navigation of arthritis care services but expressed concerns around communication and receiving minimal support for self-management of their arthritis before and after receiving specialist care. CONCLUSION: This baseline evaluation of CI and triage for arthritis care indicates satisfaction with the service, but areas that require further consideration are referral completion, timely waiting lists, and further supporting patients to self-manage their arthritis.