Objective. To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.Methods. Patients with active PsA, stratified by prior... Show moreObjective. To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.Methods. Patients with active PsA, stratified by prior anti-TNF use (naive or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random slope) at weeks 24 and 52, and observed data at week 52. Assessments at week 52 included additional efficacy endpoints (non-responders imputation and mixed-effects models for repeated measures) and safety.Results.The majority (86.6%) of patients completed 52 weeks of treatment. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS 0.5) was 91.8, 85.2 and 87.2% in 300, 150 and 150 mg no load groups, respectively, at week 52. The change in vdH-mTSS from baseline to week 52 using random slope [mean change (s.e.)] was -0.18 (0.17), 0.11 (0.18) and -0.20 (0.18) in 300, 150 and 150 mg no load groups, respectively; the corresponding observed data [mean change (s.d.)] was -0.09 (1.02), 0.13 (1.39) and 0.21 (1.15). Clinical efficacy endpoints were sustained, and no new or unexpected safety signals were reported through 52 weeks.Conclusion. Secukinumab 300 and 150 mg with or without s.c. loading regimen provided sustained low rates of radiographic progression through 52 weeks of treatment. Show less
Ramiro, S.; Landewe, R.B.M.; Heijde, D. van der; Sepriano, A.; FitzGerald, O.; Ostergaard, M.; ... ; Maksymowych, W.P. 2020
ObjectivesTo 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.MethodsRA... Show moreObjectivesTo 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.MethodsRA 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.ResultsIn 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).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission. Show less
The favourable long-term results of early treatment in patients with classified rheumatoid arthritis have resulted in an increasing interest in the diseases phases preceding clinical arthritis. The... Show moreThe favourable long-term results of early treatment in patients with classified rheumatoid arthritis have resulted in an increasing interest in the diseases phases preceding clinical arthritis. The hypothesis to test is that an intervention in these early phases may better prevent or reduce disease persistence than an intervention when arthritis has become clinically manifest. While several placebo-controlled trials are still ongoing, to date there is no firm evidence that this hypothesis truly holds. Therefore, it is important to reflect on the current status of arthralgia preceding clinical arthritis. Inherent to every new field of research, attitudes are conflicting, with opinions propagating innovation (based on the fear of undertreatment) on the one hand, and critical sounds pleading for more restraint (fear of overtreatment) on the other hand. In this Viewpoint, we will examine these divergent opinions, relate them to a preferred ultimate scenario and provide considerations for future studies and daily practice. Show less
Objectives The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients... Show moreObjectives The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients affected by axial spondyloarthritis (axSpA) worldwide.Methods An ASAS task force developed a set of QS using a stepwise approach. First, key areas for quality improvement were identified, discussed, rated and agreed on. Thereafter, areas were prioritised and statements for the most important key areas were phrased on consensus. Appropriate quality measures were defined to allow quantification of the QS at the community level.Results The ASAS task force, consisting of 20 rheumatologists, two physiotherapists and two patients, selected and proposed 34 potential key areas for quality improvement which were then commented by 140 ASAS members and patients. Within that process three new key areas came up, which led to a re-evaluation of all 37 key areas by 120 ASAS members and patients. Five key areas were identified as most important to determine quality of care: referral including rapid access, rheumatology assessment, treatment, education/self-management and comorbidities. Finally, nine QS were agreed on and endorsed by the whole ASAS membership.Conclusions ASAS successfully developed the first set of QS to help improving healthcare for adult patients with axSpA. Even though it may currently not be realistic to achieve the QS in all healthcare systems, they provide high-quality of care framework for patients with axSpA that should be aimed for. Show less
Objective To test the longitudinal association between patient-reported outcome, Routine Assessment of Patient Index Data 3 (RAPID3) and the Disease Activity Score in 28 joints that includes the... Show moreObjective To test the longitudinal association between patient-reported outcome, Routine Assessment of Patient Index Data 3 (RAPID3) and the Disease Activity Score in 28 joints that includes the erythrocyte sedimentation rate (DAS28-ESR) in routine-care patients with rheumatoid arthritis (RA).Methods Patients with RA treated with disease-modifying antirheumatic drugs were included in this prospective observational cohort. The longitudinal association between RAPID3 (0-10) and DAS28-ESR and its individual components (swollen joint count (SJC), erythrocyte sedimentation rate (ESR) (mm/hour), tender joint count (TJC) and patient global assessment (PGA)) was tested using generalised estimating equations in patients with more than two consecutive visits with data on RAPID3 and DAS28-ESR. Interactions between RAPID3 and gender, pain, PGA and age at baseline were tested, and if significant (p<0.20) and clinically relevant, models were fit in the corresponding strata.Results In total, 330 patients were included (mean follow-up 10.7 (SD 9.7) months, female gender 67.9%). The longitudinal association between RAPID3 and DAS28-ESR was weak (beta=0.29 (95% CI 0.24 to 0.35), n=207), meaning that one unit increase in RAPID3 corresponded to a 0.29 unit increase in Disease Activity Score in 28 joints (DAS28). RAPID3 was most strongly associated with subjective (TJC: beta=0.89 (95% CI 0.61 to 1.17); PGA: beta=0.94 (95% CI 0.84 to 1.04)) and not with objective components of DAS28 (SJC: beta=0.29 (95% CI 0.17 to 0.41), n=172). The association between RAPID3 and ESR was poor but modified by gender, being only significant in men (beta=0.37 (95% CI 0.08 to 0.67)).Conclusions These data suggest that RAPID3 does not sufficiently capture changes in objective inflammatory signs. Monitoring by RAPID3 alone is therefore insufficient to follow disease activity in patients wth RA in clinical practice. Show less
Putrik, P.; Ramiro, S.; Molto, A.; Keszei, A.P.; Norton, S.; Dougados, M.; ... ; Boonen, A. 2019
Objectives We aimed to evaluate the effects of methotrexate (MTX) comedication added to biological disease-modifying antirheumatic drugs (bDMARD) on disease activity measures in patients with... Show moreObjectives We aimed to evaluate the effects of methotrexate (MTX) comedication added to biological disease-modifying antirheumatic drugs (bDMARD) on disease activity measures in patients with rheumatoid arthritis (RA) in routine care.Methods Patients with RA on treatment with either bDMARDs or conventional synthetic DMARDs were included in this prospective cohort study. The effect of (time-varying) combination therapy with bDMARD and MTX compared with bDMARD monotherapy was tested in longitudinal generalised estimating equation models using as outcomes: (1) the likelihood to be in remission according to the 28-joint Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) (< 2.6) and to the Routine Assessment of Patient Index Data 3 (RAPID3) (0-30; <= 3), a patient-reported outcome measure about RA symptoms; and (2) DAS28-ESR and RAPID3 as continuous variables. All models were adjusted for potential confounders: age, gender, drugs for comorbidities (yes/no), oral steroids (yes/no) and non-steroidal anti-inflammatory drug (yes/no).Results In total, 330 patients were included (mean (SD) follow-up; 10.7 (9.7) months). Compared with bDMARD monotherapy, MTX combination therapy was significantly associated with a 55% higher likelihood to be in DAS28 remission, but not RAPID3 remission, over time. Combination therapy resulted in slightly, but statistically significant, lower levels of DAS28-ESR over time (beta=-0.42 (95% CI -0.67 to -0.17)), but not RAPID3 (beta=-0.58 (95% CI -0.65 to 0.49)). The effect on DAS28-ESR was entirely explained by lower swollen joint counts and was persistent after correction for confounders.Conclusion These results give support to the policy that MTX should be continued in routine care patients with RA on biological therapy since this leads to better objective but not subjective clinical outcomes Show less
Objective To establish in a global setting the relationships between countries' socioeconomic status (SES), measured biological disease modifying antirheumatic drug (bDMARD)-usage and disease... Show moreObjective To establish in a global setting the relationships between countries' socioeconomic status (SES), measured biological disease modifying antirheumatic drug (bDMARD)-usage and disease outcomes. To assess if prescription and reimbursement rules and generic access to medication relates to a countries' bDMARD-usage.Methods Data on disease activity and drug use from countries that had contributed at least 100 patients were extracted from the METEOR database. Mean disease outcomes of all available patients at the final visit were calculated on a per-country basis. A questionnaire was sent to at least two rheumatologists per country inquiring about DMARD-prices, access to treatment and valid regulations for prescription and reimbursement.Results Data from 20 379 patients living in 12 different countries showed that countries' SES was positively associated with measured disease activity (meanDAS28), but not always with physical functioning (HAQ-score). A lower country's SES, stricter rules for prescription and reimbursement of bDMARDs as well as worse affordability of bDMARDs were associated with lower bDMARD-usage. bDMARD-usage was negatively associated with disease activity (although not with physical functioning), but the association was moderate at best.Conclusions Disease activity in patients with rheumatoid arthritis as well as bDMARD-usage varies across countries worldwide. The (negative) relationship between countries' bDMARD-usage and level of disease activity is complex and under the influence of many factors, including-but not limited to-countries' SES, affordability of bDMARDs and valid prescription and reimbursement rules for bDMARDs. Show less
Objective. To assess differences in initial treatment and treatment response in male and female patients with rheumatoid arthritis (RA) in daily clinical practice.Methods. The proportion of... Show moreObjective. To assess differences in initial treatment and treatment response in male and female patients with rheumatoid arthritis (RA) in daily clinical practice.Methods. The proportion of patients with RA starting different antirheumatic treatments (disease-modifying antirheumatic drugs; DMARD) and the response to treatment were compared in the international, observational METEOR register. All visits from start of the first DMARD until the first DMARD switch or the end of followup were selected. The effect of sex on time to switch from first to second treatment was calculated using Cox regression. Linear mixed model analyses were performed to assess whether men and women responded differently to treatments, as measured by Disease Activity Score (DAS) or Health Assessment Questionnaire.Results. Women (n = 4393) more often started treatment with hydroxychloroquine, as monotherapy or in combination with methotrexate (MTX) or a glucocorticoid, and men (n = 1142) more often started treatment with MTX and/or sulfasalazine. Time to switch DMARD was shorter for women than for men. Women had a statistically significantly higher DAS over time than men (DAS improvement per year beta -0.69, 95% CI -0.75 to -0.62 for men and -0.58, 95% CI -0.62 to -0.55 for women). Subanalyses per DMARD group showed for the conventional synthetic DMARD combination therapy a slightly greater decrease in DAS over time in men (-0.89, 95% CI -1.07 to -0.71) compared to women ( 0.59, 95% CI 0.67 to 0.51), but these difference between the sexes were clinically negligible.Conclusion. This worldwide observational study suggests that in daily practice, men and women with RA are prescribed different initial treatments, but there were no differences in response to treatment between the sexes. Show less
Ortolan, A.; Lunteren, M. van; Ramiro, S.; Ramonda, R.; Landewe, R.B.M.; Dagfinrud, H.; ... ; Gaalen, F.A. van 2018
