Johan Karlsson Wallman

Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial

Objectives In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up. Methods A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2. Results Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30–44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy. Conclusions Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP. Trial registration number NCT00764725.

Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients--baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice.

BackgroundThe relationship between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) is currently debated. Using observational data from the South Swedish Arthritis Treatment Group register, we thus aimed to compare clinical development and treatment adherence between nr-axSpA and AS patients during three years of anti-TNF (tumor necrosis factor) therapy in clinical practice, and to explore the impact of inflammatory activity measured by CRP (C-reactive protein) at treatment initiation.MethodsNr-axSpA and AS patients (n = 86/238) in southern Sweden, commencing anti-TNF therapy 1999-2011, were followed during three years. Anti-TNF cessation was defined as stopping therapy, without restarting another anti-TNF agent within three months. Differences in the three year developments of patient’s visual analogue scale (VAS) scores for global health and pain, EuroQol 5-Dimensions utility, evaluator’s global disease activity assessment, CRP, and ESR (erythrocyte sedimentation rate) were assessed by repeated ANOVA. Anti-TNF adherence was compared by Log rank test and Cox regression. In a subanalysis, the same outcomes were studied after splitting both groups into patients with/without baseline CRP elevation.ResultsNr-axSpA patients were more often female and had lower acute phase reactants at baseline. Apart from CRP, which remained lower in the nr-axSpA group throughout follow-up (p = 0.004), no between-group differences were detected regarding clinical developments (p >0.1 for all comparisons) or anti-TNF adherence (hazard ratio: 1.1 (95 % CI 0.7 to 1.8) for the nr-axSpA vs. AS group) during three years. Elevated baseline CRP was similarly associated with superior clinical outcomes and treatment adherence in both groups.ConclusionsWith the exception of constantly lower CRP levels in the nr-axSpA group, three years anti-TNF therapy resulted in similar clinical outcomes and treatment adherence in nr-axSpA and AS patients, thus strengthening the hypothesis that these diagnoses represent different aspects/phases of the same disease.

Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis: Observational Data from Southern Sweden

Objective. To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA). Methods. Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005–2010. Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register-derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare (patient care and drugs) and work loss costs (patients < 65 yrs) were studied in separate regression models, comparing standardized β coefficients by nonparametric bootstrapping to assess which measure best reflects costs. Analyses were conducted based on both individual means (linear regression, comparing between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs. Results. Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work loss costs were also more closely associated with EQ-5D than DAS28. The results of the linear models for healthcare costs were standardized β = 0.21 (95% CI 0.15–0.27), 0.16 (0.11–0.21), and –0.15 (−0.21 to −0.10) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D). For work loss costs, the results were standardized β = 0.43 (95% CI 0.39–0.48), 0.27 (0.23–0.32), and −0.34 (−0.38 to −0.29) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D and for EQ-5D vs DAS28). Conclusion. Overall, HAQ disability is a better marker of RA costs than DAS28 or EQ-5D HRQOL.

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure

To investigate whether the Multi‐Biomarker Disease Activity (MBDA) score predicts optimal add‐on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX‐IRs).

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.

Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden

Objective The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Methods Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. Results The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Conclusion Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up.

Infliximab Versus Conventional Combination Treatment and Seven-Year Work Loss in Early Rheumatoid Arthritis : Results of a Randomized Swedish Trial

To compare long‐term work loss in methotrexate‐refractory early rheumatoid arthritis (RA) patients randomized to the addition of infliximab or conventional combination treatment.

Infliximab versus Conventional Combination Treatment and 7‐Year Work Loss in Early RA: Results of the Randomized Swefot Trial

To compare long‐term work loss in methotrexate‐refractory early rheumatoid arthritis (RA) patients randomized to the addition of infliximab or conventional combination treatment.

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

To study the impact of common noncomposite disease activity measures on sick leave in biologics‐treated patients with rheumatoid arthritis (RA).

OP0133 Unacceptable, refractory pain despite inflammation control in early rheumatoid arthritis and its relation to treatment strategy: results from the randomised controlled swefot trial

Background Pain is a major concern of RA patients and earlier work has defined the level considered not acceptable by patients (unacceptable pain according to the patient acceptable symptom state (PASS)1). While a lot of focus has been put on the occurrence and management of inflammatory pain, less is reported on refractory pain despite inflammation control, and its pattern in early RA. Objectives The aim of this study was to investigate the prevalence of unacceptable pain despite inflammation control during the first 2 years after treatment start in new-onset RA patient and to compare the impact of biological vs conventional combination therapy on the occurrence of this pain status. Methods The SWEFOT (SWedish FarmacOTherapy) trial was designed as a randomised, active-controlled, open-label study, enrolling early (<1 year) RA patients Oct 2002 to Dec 2005 After a 3 month run-in period on methotrexate (MTX), patients reaching DAS28 ≤3.2 continued monotherapy (n=147), while the others were randomised to addition of infliximab (IFX; n=128) or sulfasalazine +hydroxychloroquine (SSZ+HCQ; n=130). Results for disease activity and radiographic data were published earlier. Here, we used a measure of unacceptable pain despite inflammation control as outcome (combining VAS pain >40 mm1–100 with CRP <10 mg/L,2 and ≤1 swollen joint (of 28)). When comparing the randomised arms, last observation carried forward in case of protocol breach was used, while for analyses of the whole material we used all data irrespective of protocol breach. Differences in prevalence were analysed by Mc Nemar’s test, while differences between patients randomised to IFX vs SSZ+HCQ as well as between EULAR response groups were estimated by logistic regression, adjusting for age, sex and VAS pain at baseline. Results In the whole material (including all 3 groups, n=405), the frequency of unacceptable pain despite inflammation control increased gradually from inclusion, reached 12% at 1 year (difference from inclusion; p<0.001), and then remained stable until the 2 year follow-up; at that point accounting for more than half of all unacceptable pain (figure 1). The frequency was unrelated to EULAR response from inclusion to the 2 year follow-up (11.4% of good responders vs 10.4% of non-responders, p=0.95). Furthermore, no difference in unacceptable pain despite inflammation control at 2 years was found between patients randomised to IFX vs SSZ+HCQ, (adjusted odds ratio 1.1 [95% CI: 0.5 to 2.4]; p=0.75). Conclusions After 2 years of early active treatment in new-onset RA patient, a substantial portion had unacceptable pain despite inflammation control. This pain status was as common in EULAR good responders as in non-responders and no difference was found between patients randomised to IFX compared to SSZ+HCQ. These data are in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain in a subgroup of patients, strongly warranting alternative treatment strategies in these patients. References [1] Tubach, et al. Arthritis Care Res2012;64:1699–70. [2] Lourdudoss, et al. Arthritis Care Res. doi:10.1002/acr.23245 Disclosure of Interest T. Olofsson: None declared, J. Wallman Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, UCB, A. Jöud: None declared, M. Schelin: None declared, S. Ernestam: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, UCB, Consultant for: AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, UCB, S. Saevarsdottir: None declared, J. Lampa Grant/research support from: AbbVie, Speakers bureau: AbbVie, Eli Lilly, Hospira, MSD, Novartis, Pfizer, Roche, Sandoz, UCB