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
Objectives To compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA).Methods Five-year outcomes were... Show moreObjectives To compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA).Methods Five-year outcomes were compared in 133 patients with early active RA (1987), starting with methotrexate, sulfasalazine and tapered high dose of prednisone (arm 3 of the BehandelStrategieen (Treatment Strategies for Rheumatoid Arthritis) (BeSt) study), targeted at Disease Activity Score (DAS) <= 2.4 (low disease activity), and 175 patients with early RA, starting methotrexate and tapered high dose of prednisone, targeted at DAS <1.6 (selected from IMPROVED study who would have fulfilled inclusion criteria of the BeSt study). Association of treatment target with outcomes DAS <1.6, Boolean remission at year 1 and drug-free DAS remission (DFR) at year 5 were analysed by logistic regression analysis.Results At baseline, DAS <1.6 steered patients had a milder disease than DAS <= 2.4 steered patients (mean DAS 4.1 +/- SD 0.7vs4.4 +/- 0.9, p=0.012) and less radiological damage. DAS decrease, functional ability and radiological damage progression over time were similar in both patient groups. DAS <= 2.4 was achieved in similar percentages in both patient groups, but more DAS <1.6 steered patients achieved DAS <1.6 and DFR. DAS <1.6 steered treatment was associated with achieving DAS <1.6 (OR 3.04 (95% CI 1.64 to 5.62)) and Boolean remission (3.03 (1.45 to 6.33)) at year 1 and DFR at year 5 (3.77 (1.51 to 9.43)).Conclusions In patients with early active RA who start with comparable disease-modifying antirheumatic drug+prednisone combination therapy, subsequent DAS <1.6 steered treatment is associated with similar clinical and radiological outcomes over time as DAS <= 2.4 steered treatment; however, in the DAS <1.6 steered group, more patients achieved remission and drug-free remission. Show less
BACKGROUND: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in... Show moreBACKGROUND: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy.METHODS: We compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment.RESULTS: Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received.CONCLUSIONS: Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians' research question is in line with preferences of the patient-group. By exploring so-called 'informed patient-group'-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. Show less
Bergstra, S.A.; Allaart, C.F.; Berg, R. van den; Chopra, A.; Govind, N.; Huizinga, T.W.J.; Landewe, R.B.M. 2017
