Anti-rheumatic treatment and prosthetic joint infection: an observational study in 494 elective hip and knee arthroplasties.

BACKGROUND: Surgical site infections are more frequent among patients with rheumatic disease. To what extent this is related to immunosuppressive antirheumatic drugs is unclear, as is the value of discontinuing medication perioperatively. The aim of study was to assess the rate of surgical site infections after knee and hip replacement in patients with inflammatory joint disease, with an emphasis on periprosthetic joint infection, and to investigate the influence of treatment with disease-modifying antirheumatic drugs (DMARDs) in this regard. METHODS: Data were collected from 494 primary elective hip (51.4%) and knee arthroplasties, along with demographic and medication data. The primary outcome was surgical site infection during the first year after surgery. RESULTS: In 78% (n = 385) of the cases the patient used 1 to 3 disease-modifying antirheumatic drugs perioperatively. Thirty-two percent (n = 157) of patients used a TNF-alpha inhibitor. The rate of surgical site infection was 3.8% (n = 19). The rate of periprosthetic joint infection was 1.4% (n = 7), all of which occurred after knee arthroplasty. Periprosthetic joint infection occurred in only 1 patient medicating perioperatively with a TNF-alpha inhibitor. CONCLUSION: Surgical site infections were not associated with ongoing medication with disease-modifying antirheumatic drugs. Due to the low event rate this should be interpreted with caution, but our center will maintain its routine of continuing treatment with TNF-alpha inhibitors perioperatively.

Patient-Reported Outcomes Are More Important Than Objective Inflammatory Markers for Sick Leave in Biologics-Treated Patients With Rheumatoid Arthritis.

OBJECTIVE: To study the impact of common noncomposite disease activity measures on sick leave in biologics-treated patients with rheumatoid arthritis (RA). METHODS: Data from study visits by biologics-treated RA patients of working age (<65 years) in the observational South Swedish Arthritis Treatment Group Register between 2005 and 2011, were included (5,118 visits by 941 patients). We performed association analyses between various noncomposite disease activity measures at each visit and the number of days of sick leave during the subsequent month; this information was retrieved from the Social Insurance Agency. Adjusted separate generalized estimating equation regression models were used, and analyses were stratified according to sick leave status for the month preceding each visit (no, partial, or full sick leave). Results are presented as standardized beta coefficients for comparability. RESULTS: Among modifiable noncomposite disease activity measures, patient's assessment of pain and disease activity scored on a visual analog scale (VAS) were most strongly associated with subsequent sick leave, irrespective of baseline sick leave status. Generally, measures that were more objective (swollen joint count, erythrocyte sedimentation rate, and C-reactive protein) had less impact on sick leave compared with variables that were more subjective (patient's pain and global scores on a VAS, evaluator's global assessment of disease activity on a 5-grade Likert scale, and tender joint count). CONCLUSION: Measures of disease activity that are more subjective have a greater impact on sick leave in biologics-treated patients with RA compared with variables that are more objective, suggesting a stronger focus on subjective measures when targeting work loss or intervening to reduce it.

EuroQol-5 dimensions utility gain according to British and Swedish preference sets in rheumatoid arthritis treated with abatacept, rituximab, tocilizumab, or tumour necrosis factor inhibitors: a prospective cohort study from southern Sweden.

BACKGROUND: The development of EuroQol-5 dimensions (EQ-5D) utility over time in rheumatoid arthritis (RA) patients, treated with biologics other than tumour necrosis factor inhibitors (TNFi), based on the standard British (UK) and the new Swedish (SE) EQ-5D preference sets, has not been previously described. METHODS: Demographics, core set data, EQ-5D utility, and treatment characteristics for patients with established RA, receiving biologics in southern Sweden from January 2006 to March 2014, were retrieved from observational databases. Theoretical, UK, and experience-based, SE, EQ-5D mean utilities were plotted over time. RESULTS: Data regarding 2418 treatment courses with abatacept (ABA, n = 100), rituximab (RTX, n = 230), tocilizumab (TOC, n = 121), or TNFi (n = 1967) were included in the analysis. Patients starting TNFi treatment, as expected, had shorter disease duration and less previous biologics. Baseline utilities of patients commencing ABA and TOC, but not RTX, were also lower than in the TNFi group. Following treatment initiation, rapid utility improvements were seen with all therapies, reaching plateaus after approximately 1.5 months, and then remaining fairly stable throughout follow-up in patients adhering to therapy. SE utilities were consistently higher than UK, with baseline values at around 0.7 leaving little room for improvement. CONCLUSIONS: ABA, RTX, TOC, and TNFi treatments were all associated with favourable EQ-5D utility developments in RA patients adhering to therapy. The compression of the experience-based SE preference set towards higher utilities may compromise its ability to detect between-group differences in quality-adjusted life-years, thus making cost-effectiveness harder to demonstrate in cost-utility analyses applying this preference set, rather than the standard UK.

Is swollen to tender joint count ratio a new and useful clinical marker for biologic drug response in rheumatoid arthritis? Results from a Swedish cohort.

OBJECTIVE: To study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. METHODS: Patients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 ≤ STR ≤ 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. RESULTS: A total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. CONCLUSION: STR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.

Continuation of TNF blockade in patients with inflammatory rheumatic disease. An observational study on surgical site infections in 1,596 elective orthopedic and hand surgery procedures.

BACKGROUND: Increased infection risk in inflammatory rheumatic diseases may be due to inflammation or immunosuppressive treatment. The influence of tumor necrosis factor (TNF) inhibitors on the risk of developing surgical site infections (SSIs) is not fully known. We compared the incidence of SSI after elective orthopedic surgery or hand surgery in patients with a rheumatic disease when TNF inhibitors were continued or discontinued perioperatively. PATIENTS AND METHODS: We included 1,551 patients admitted for elective orthopedic surgery or hand surgery between January 1, 2003 and September 30, 2009. Patient demographic data, previous and current treatment, and factors related to disease severity were collected. Surgical procedures were grouped as hand surgery, foot surgery, implant-related surgery, and other surgery. Infections were recorded and defined according to the 1992 Centers for Disease Control definitions for SSI. In 2003-2005, TNF inhibitors were discontinued perioperatively (group A) but not during 2006-2009 (group B). RESULTS: In group A, there were 28 cases of infection in 870 procedures (3.2%) and in group B, there were 35 infections in 681 procedures (5.1%) (p = < 0.05). Only foot surgery had significantly more SSIs in group B, with very low rates in group A. In multivariable analysis with groups A and B merged, only age was predictive of SSI in a statistically significant manner. INTERPRETATION: Overall, the SSI rates were higher after abolishing the discontinuation of anti-TNF perioperatively, possibly due to unusually low rates in the comparator group. None of the medical treatments analyzed, e.g. methotrexate or TNF inhibitors, were significant risk factors for SSI. Continuation of TNF blockade perioperatively remains a routine at our center.

Individualized outcome measures of daily activities are sensitive tools for evaluating hand surgery in rheumatic diseases.

OBJECTIVES: To explore the ability of six outcome measures to capture clinically important changes in patients with rheumatic diseases undergoing hand surgery and to study predictors of changes in activity performance in different patient and surgery strata. METHODS: A total of 172 patients (median age 59 years, disease duration 18 years) were stratified into subgroups: diagnosis, age, general function, type of surgery. Performance of daily activities and satisfaction were assessed by the Canadian Occupational Performance Measure (COPM). Clinically important improvement was defined as a two-step improvement in COPM. Hand function was assessed by reference to grip strength (Grippit), pinch strength (pinch gauge), hand pain (visual analogue scale) and grip ability (Grip Ability Test). Responsiveness was calculated as effect size (ES) at 6-month follow-up compared with baseline. RESULTS: Clinically important improvement was reached by 25-69% depending on outcome measure and type of surgery. Improvement was smaller in patients with multiple simultaneous procedures. Regardless of diagnosis, age, general function and type of surgery, patients improved significantly in all measures, with the largest changes in COPM(performance) and COPM(satisfaction) (ES 0.7-1.9). The ES of pain ranged from 0.2 to 0.7, Grippit from 0.1 to 0.5 and pinch gauge from 0.4 to 0.8. Hand pain was the only significant predictor of clinically important improvement of COPM(performance): odds ratio 0.71, 95% CI 0.51, 0.98 (P = 0.041). CONCLUSION: COPM was the most sensitive instrument to capture clinically important improvement, and hand pain was a significant predictor of improvement, irrespective of diagnosis, age, general functional level and type of surgery.

National EQ-5D tariffs and quality-adjusted life-year estimation: comparison of UK, US and Danish utilities in south Swedish rheumatoid arthritis patients.

OBJECTIVE: To study how the choice of national EQ-5D tariff may affect utility and incremental quality-adjusted life-year (QALY) estimates. METHODS: South Swedish rheumatoid arthritis patients in an observational study, starting and continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ-5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs. Utilities for all 243 possible EQ-5D health states were also compared. RESULTS: US utilities were generally higher than UK, with Danish falling in between. A substantial 1-year mean utility improvement was seen in both study groups using all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting for baseline differences between groups, the incremental QALY gain of combined treatment was 0.09 using the UK tariff, while 0.06 according to both US and Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied irregularly across the range of utilities. CONCLUSIONS: Applying different national EQ-5D tariffs to the same data may result in substantially different incremental QALY estimates, crucial knowledge when interpreting cost-utility analyses. Studies using different tariffs cannot be directly compared.

Utility-based outcomes made easy: the number needed per quality-adjusted life year gained. An observational cohort study of tumor necrosis factor blockade in inflammatory arthritis from Southern Sweden.

OBJECTIVE: To introduce a novel, simple, utility-based outcome measure, the number needed per quality-adjusted life year (QALY) gained (NNQ), and to apply it in clinical practice in anti-tumor necrosis factor (anti-TNF)-treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA). METHODS: The NNQ is the number of patients one has to treat in order to gain 1 QALY. It is calculated as the inverted value of the utility gain (area under the curve) over 1 year in a cohort subjected to an intervention. EuroQol Index utility data from the South Swedish Arthritis Treatment register were used. RESULTS: Patients with RA (n = 1,001), PsA (n = 241), and SpA (n = 255) were eligible for the study. First, second, and third treatment courses were studied. For RA, NNQ was 4.5, 6.4, and 5.2 for first, second, and third courses, respectively. For PsA and SpA, NNQ was 4.2-4.5, irrespective of treatment order. Treatment groups with <50 patients were not analyzed. During the study period 2002-2007, there were no secular trends of utility gains. CONCLUSION: The NNQ is an easily derived and understandable utility-based outcome measure that may be useful for stakeholders and decision makers as well as for clinicians. It was readily applied in this study of TNF blockade across 3 arthritis diagnoses. NNQ varied little over diagnoses and treatment course order, with a possible exception in second treatment course in RA.

Disease activity level, remission and response in established rheumatoid arthritis: performance of various criteria sets in an observational cohort, treated with anti-TNF agents.

BACKGROUND: Most composite indices of disease activity and response criteria in RA have been validated and compared in clinical trials rather than routine care. We therefore wanted to compare the performance of the DAS28, SDAI and CDAI activity indices, their activity states, their response criteria, and also compare with the ACR response criteria in an observational clinical setting. METHODS: Agreement between the criteria sets was investigated using kappa statistics in a non-randomized cohort of 1789 RA patients from southern Sweden, starting their first course of anti-TNF-treatment. Mean disease duration was 12 years. Completer analysis was used. RESULTS: Agreement between high, moderate and low activity states was moderate or substantial, with kappa = 0.5 or better for all criteria. Agreement between SDAI and CDAI disease states was > 90% in these categories with kappa > 0.8. DAS28 original and modified cut point remission had good agreement (kappa = 0.91). Agreement between responses was substantial at the overall/ACR20 level (about 95%, kappa = 0.7 or better) for all criteria. By contrast, agreement was poor between moderate and high level responses. CONCLUSION: Disease activity states according to the various indices perform similarly and show substantial agreement at all levels except remission. Agreement between SDAI and CDAI states is excellent. Response criteria, applied at the individual patient level, are hard to interpret and show poor agreement, except at the lowest level of response. Thus, they should not be applied uncritically in clinical practice.

Six and 12 weeks treatment response predicts continuation of tumor necrosis factor blockade in rheumatoid arthritis: an observational cohort study from southern Sweden.

OBJECTIVE: To investigate if treatment response predicts continuation of anti-tumor necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: We investigated if treatment response and/or achieving a certain activity state at 6 weeks or 3 months predicts continuation of treatment in an observational cohort of 1789 anti-TNF-naive patients with established RA disease from southern Sweden. RESULTS: Response to treatment at 6 weeks at overall/American College of Rheumatology (ACR20) or good/major level (except ACR70) significantly predicted drug continuation. Response according to all criteria sets at overall/ACR20 and at good/major/ACR70 level predicted drug continuation at 3 months, as did achieving low disease activity at 3 months irrespective of activity index applied. Remaining in a high disease activity state predicted drug discontinuation at both timepoints and according to all criteria sets. CONCLUSION: Response criteria may be useful aids in deciding on continuation of TNF blockade in RA as early as after 6 weeks of treatment. The various criteria sets perform similarly.

Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors, compared to a standard RA population. METHODS: Patients were recruited from a regional register, which includes over 90% of patients with RA started on TNF blockers in 1999 or later, and a local community based cohort of RA patients, established in 1997. Of a total of 983 patients in the combined cohort, 531 received treatment with etanercept or infliximab during the study period. The total cohort (n = 983) was linked with national registers for inpatient care and cause of death through December 31, 2001. CVD was defined as the first inpatient care or death from CVD without inpatient care for CVD prior to study entry. First CVD events in those treated versus not treated with TNF blockers were estimated, using age and sex adjusted incidence density computations with treatment and disease severity markers as time-dependent covariates. RESULTS: In the anti-TNF-treated patients, the age-sex adjusted incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7-22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46 (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated. CONCLUSION: These findings suggest that the risk of developing CVD is lower in patients with RA treated with TNF blockers. This is compatible with the hypothesis that inflammation contributes to the development of cardiovascular events.