What PASSes for good? Experience-based Swedish and hypothetical British EuroQol 5-Dimensions preference sets yield markedly different point estimates and patient acceptable symptom state cut-off values in chronic arthritis patients on TNF blockade.

OBJECTIVES: Health utilities derived from answers to generic health-related quality of life (HRQoL) questionnaires such as the EuroQol 5-Dimensions (EQ-5D) are often used in cost-utility analyses (CUAs) of new and expensive treatments. Different preference sets (tariffs) used in the computation of utility values and quality-adjusted life-years (QALYs) from questionnaire responses (health states) yield varying results, potentially affecting decisions of resource allocation. The objective of the present study was to compare British (UK), hypothetical, and Swedish (SE), experience-based, EQ-5D utilities using data from clinical practice. METHOD: UK and SE EQ-5D utilities were computed in an observational cohort of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) treated with tumour necrosis factor (TNF) blockers, comparing point estimates and patient acceptable symptom state (PASS) cut-off levels. RESULTS: SE utilities were found to be consistently higher than UK utilities, and PASS cut-offs were essentially stable over time. CONCLUSIONS: With higher baseline utilities, there may be less room for improvement after an intervention and thus less accumulation of QALYs in CUAs applying the SE, as opposed to the UK, EQ-5D tariff.

Efficacy and drug survival of anti-tumour necrosis factor-alpha therapies in patients with non-radiographic axial spondyloarthritis: an observational cohort study from Southern Sweden.

OBJECTIVES: To evaluate the efficacy and drug survival of anti-tumour necrosis factor (anti-TNF) therapy in non-radiographic axial spondyloarthritis (nr-axSpA) patients treated in clinical practice in Southern Sweden. METHOD: In this cohort study we prospectively included 112 patients with nr-axSpA and high disease activity as well as inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) receiving their first course of anti-TNF therapy. Patients fulfilling modified New York criteria for ankylosing spondylitis (AS) were excluded. The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial SpA were fulfilled by 77% (n = 86) of the included patients. RESULTS: At baseline, the median age of the cohort was 38 years, 59% were males, 79% of the patients had imaging suggestive of sacroiliitis (primarily inflammation on magnetic resonance imaging, MRI), 71% were HLA-B27 positive, and the median disease duration was 6 years and 10 months. At 6 months of follow-up, the median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.6 to 3.2 (p = 0.002), the Bath Ankylosing Spondylitis Functional Index (BASFI) decreased from 3.9 to 1.8 (p = 0.005), and C-reactive protein (CRP) level decreased from 4.4 to 1.7 mg/L (p = 0.001). After 1 year of treatment the Kaplan-Meier estimated drug survival was 76%, and at 2 years of follow-up this value decreased to 65%. Patients with inflammatory MRI findings at baseline had significantly better drug survival [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.10-0.55, p = 0.001]. Male sex was also associated with higher drug survival (HR 0.45, 95% CI 0.24-0.85, p = 0.011). CRP level at baseline was not associated with drug survival. CONCLUSIONS: Anti-TNF treatment of patients with nr-axSpA in clinical practice resulted in reduced BASDAI and BASFI scores and good drug survival. The results from this study suggest that male gender and positive imaging at baseline are associated with a favourable treatment course.

Rapid and sustained health utility gain in anti-tumour necrosis factor-treated inflammatory arthritis: observational data during 7 years in southern Sweden.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondylarthritides impose a great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry-independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing tumour necrosis factor (TNF) blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures and to compare them across diagnostic entities. METHODS: EuroQoL 5 dimensions (EQ-5D) utility data were collected from a structured clinical follow-up programme of anti-TNF-treated patients with RA (N = 2554), PsA (N = 574) or spondylarthritides (N = 586). Time trends were calculated. Completer analysis was used. RESULTS: There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and spondylarthritides. The maximum gain in utilities had already occurred after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. The first and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and spondylarthritides over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and spondylarthritides. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.

Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register.

OBJECTIVE: To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences. METHODS: Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled. The study period was March 1999 through September 2006. The prospective protocol included information on demographics, clinical characteristics of patients and response measures. Fulfilment of ACR 50-70% improvement and European League Against Rheumatism (EULAR) good response or remission [28-joint disease activity score (DAS28) <2.6] at 3 months were chosen as primary outcome measures. Potential predictors of responses were identified using multivariate binary logistic regression models. RESULTS: In total, 1565 patients were included in the study. Gender did not influence treatment response. Consistently, concomitant methotrexate (MTX) was significantly associated with EULAR remission, EULAR good response, ACR50 response and ACR70 response with odds ratios (ORs) 1.97, 2.13, 2.10 and 1.75, respectively. Concurrent treatment with other DMARDs was also significantly associated with EULAR remission, EULAR good response and ACR50 response (OR: 1.96, 2.24 and 1.94, respectively). Likewise, low HAQ at baseline consistently predicted good clinical outcome. Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 (OR: 1.59 and 1.60, respectively), whereas DAS28 score at baseline was inversely associated with EULAR remission (OR: 0.78). CONCLUSIONS: In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response. Choice of outcome measures may influence the predictive value of baseline features.

Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register.

OBJECTIVES: To study treatment response rates of RA patients undergoing second- and third-line anti-TNF therapy and to identify baseline predictors of response to second-line treatment. METHODS: RA patients monitored in a prospective, observational study, having switched anti-TNF therapy once (first-time switchers, n = 337) or twice (second-time switchers, n = 36)--i.e. following failures with one antibody- and one receptor-type agent--between March 1999 and December 2006, were studied. Treatment responses at 3 months were assessed by the ACR and European League Against Rheumatism (EULAR) response criteria. Predictive potentials for response to second-line treatment of demographics, baseline disease activity measures, disease and treatment characteristics were analysed using logistic regression. RESULTS: ACR20 response was met by 51% of first-time and 35% of second-time switchers. Corresponding ACR50 rates were 27 and 18%; EULAR overall rates (EULAR good or moderate response) 71 and 58%; EULAR good rates 25 and 9% and 28-joint disease activity score (DAS28) remission rates 16 and 6%. Identified baseline predictors of response to second-line treatment were lower age and HAQ scores, elevated DAS28 values and having ceased the former anti-TNF treatment due to adverse events rather than inefficacy. No variable was predictive for all examined response criteria. CONCLUSIONS: Response rates of first-time anti-TNF switchers are somewhat below those of anti-TNF naïve RA patients, while the markedly inferior response rates of second-time switchers suggest other therapeutic options to be considered in this situation. Identified baseline predictors of response may be useful indicators to second-line anti-TNF therapy, but vary depending on the response criteria set studied.

Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register.

BACKGROUND: The use of tumour necrosis factor (TNF) blocking agents in psoriatic arthritis (PsA) is increasing, and the SSATG register has followed patients with PsA for more than 5 years. The aim of the present work therefore was to present efficacy and tolerability data of TNF-blocking agents on PsA in clinical practice, and to study potential predictors for drug survival (the length of time a patient continues to take a particular drug). MATERIALS AND METHODS: Patients (n = 261) with active PsA, starting anti-TNF therapy for the first time in southern Sweden, were included. Basal characteristics, disease activity measures, and termination reason for blockers were prospectively collected during the period April 1999 to September 2006. Cox proportional hazard models were used to investigate predictors for treatment termination. RESULTS: Overall, response rates at 3-12 months for global visual analogue scale (VASglobal50) and pain VAS (VASpain50) were about 50%, whereas response rates for European League Against Rheumatism (EULAR) scoring "overall" and EULAR "good" were around 75% and 55%, respectively. Concomitant methotrexate (MTX) (hazard ratio (HR) 0.64, 95% CI 0.39-0.95, p = 0.03), etanercept (HR 0.49, 95% CI 0.28-0.86, p = 0.01), and high C-reactive protein (CRP) levels (HR 0.77, 95% CI 0.61-0.97, p = 0.03) at treatment initiation were associated with better overall drug survival. The improved drug survival of concomitant MTX appeared to be related to significantly fewer dropouts because of adverse events (HR = 0.24 (0.11-0.52), p<0.01). The blockers were well tolerated with a rate of serious adverse events of 5-6% per year. No unexpected serious adverse events were observed. CONCLUSION: Concomitant MTX and high CRP levels are associated with treatment continuation of anti-TNF therapy in patients with PsA regardless of joint distribution. The positive effect of MTX was primarily linked to fewer dropouts because of adverse events.

Response criteria for rheumatoid arthritis in clinical practice: how useful are they?

OBJECTIVE: To compare the performance of the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and simple disease activity index (SDAI) response criteria for rheumatoid arthritis at the individual level in an observational cohort. METHODS: 184 outpatients were followed using a structured protocol. For each patient, the responses according to ACR 20% and 50%, EULAR moderate and good, and SDAI minor and major responses were calculated. For comparison, improvements in health assessment questionnaire (HAQ) score of 0.22 and 0.5 were calculated. The numbers of individuals fulfilling the criteria at each level were compared, and the numbers fulfilling any two sets of response criteria calculated. The EULAR "moderate" and "good" responses were grouped together as "overall," and SDAI "minor" and "major" were merged into SDAI "overall". RESULTS: All 94 ACR 20 responders were found in the EULAR and SDAI "overall" response groups, and 118 of 124 SDAI "overall" responders were found in the EULAR "overall" group. In contrast, of 53 ACR 50 responders, only 34 were found in the EULAR "good" or SDAI "major" group. Among the 56 patients in the EULAR "good" response group, only 26 met the SDAI "major" response. Improvement in HAQ score performed similarly to the other response criteria sets at the group levels. CONCLUSIONS: For individual patients, agreement is good at the level of ACR 20 response, when EULAR overall, SDAI overall, or HAQ 0.22 criteria are applied. Agreement between ACR 50, EULAR good, SDAI major, and HAQ 0.5 response is poor. This should be considered when response criteria are used for clinical decisions.

Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas.

OBJECTIVE: To determine whether TNF blockers increase tumour risk in patients with RA. MATERIALS AND METHODS: The South Swedish Arthritis Treatment Group register (SSATG) comprises over 90% of anti-TNF treated patients with RA in the area. 757 patients treated with etanercept or infliximab included between 1 February 1999 and 31 December 2002 were identified. 800 patients with conventional antirheumatic treatment in a community based cohort served as a comparison cohort. Tumours and deaths were identified in the cancer registry and population census registers. Patients were followed up from initiation of anti-TNF treatment or 1 July 1997 for the comparison group, until death or 31 December 2002. RESULTS: In the anti-TNF group, 16 tumours (5 lymphomas) were identified in 1603 person-years at risk, and in the comparison group 69 tumours (2 lymphomas) in 3948 person-years. Standardised incidence ratios (SIRs) for total tumour relative risk for the anti-TNF group and the comparison group were 1.1 (95% confidence interval (CI) 0.6 to 1.8) and 1.4 (95% CI 1.1 to 1.8), respectively. The lymphoma relative risk (RR) was 11.5 (95% CI 3.7 to 26.9) and 1.3 (95% CI 0.2 to 4.5), respectively The total tumour RR excluding lymphoma was 0.79 (95% CI 0.4 to 1.42) and 1.39 (95% CI 1.08 to 1.76), respectively. Proportional hazard analysis for lymphomas yielded RR 4.9 (95% CI 0.9 to 26.2) in anti-TNF treated versus untreated patients. CONCLUSION: Community based patients with RA treated conventionally had an increased overall tumour risk compared with the background population. A possible additional increased risk for lymphoma associated with TNF blockers was based on few cases and needs confirmation.

Release of cartilage and bone macromolecules into synovial fluid: differences between psoriatic arthritis and rheumatoid arthritis.

OBJECTIVE: To elucidate whether differences in the destructive tissue process in cartilage and bone in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) can be recognised by different release patterns of molecular fragments derived from joint tissue. METHODS: Aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) were quantified by immunoassays in knee joint synovial fluid samples. These were obtained early in the disease course of patients with PsA and RA. At the time of arthrocentesis radiographs of their knee and hip joints were normal. RESULTS: At follow up no destruction had developed in the knees and hips of most patients with PsA (n=18), whereas the patients with RA could be separated into one "destructive" group (n=18) and one "non-destructive" group (n=25). Patients with PsA had low synovial fluid aggrecan concentrations (p<0.001 v the RA destructive group) but high COMP concentrations (p<0.01 and p<0.05 v destructive and non-destructive RA groups, respectively). Consequently, the aggrecan/COMP ratio was lowest in the PsA group (p<0.001 and p<0.01 v the destructive and non-destructive RA group, respectively). The synovial fluid concentrations of BSP did not differ between the three patient groups. CONCLUSIONS: The release pattern of aggrecan and COMP, reflecting cartilage turnover, differed between the PsA group and, particularly, the destructive RA group. This suggests that different pathophysiological mechanisms for cartilage involvement operate in these conditions, with different destructive potential. The BSP concentrations did not differ between the patients groups, which indicates similar levels of bone involvement.