Joint inflammation tends to recur in the same joints during the rheumatoid arthritis disease course.

OBJECTIVES: We investigated whether local joint swelling recurs in the same joints over time in patients with rheumatoid arthritis (RA) who are treated to target. METHODS: Patients with newly diagnosed RA participating in the Behandel-Strategieën, "treatment strategies" (BeSt) study (n=508) were followed for median 10 years while receiving Disease Activity Score (DAS) ≤2.4 steered treatment. Every 3 months 68 joints were assessed for the presence of swelling. We evaluated whether baseline local joint swelling was predictive for swelling in the same joint during follow-up using a multilevel mixed-effect logistic regression model. Different strategies were used to account for missing data. A permutation test was performed to assess if joint swelling was better predicted by baseline swelling of the joint itself than by baseline swelling of randomly selected other joints. RESULTS: In 46% of the joints that were swollen at baseline, joint swelling later recurred at least once during follow-up. Joint swelling at baseline was statistically significantly associated with swelling in the same joint during follow-up (OR 2.37, 95% CI 2.30 to 2.43, p<0.001), and also specifically with recurrent swelling in the same joint (OR 1.73, 95% CI 1.37 to 1.59, p<0.001). Local joint swelling was better predicted by baseline swelling of that particular joint than by baseline swelling of other joints (p<0.001). CONCLUSION: Joint swelling tends to recur locally in the joints swollen at RA onset. This suggests that local factors influence the manifestation of joint inflammation over time.

Long-Term Outcomes of Patients With Recent-Onset Rheumatoid Arthritis After 10 Years of Tight Controlled Treatment: A Randomized Trial.

BACKGROUND: Treat-to-target therapy is effective for patients with rheumatoid arthritis (RA), but long-term results of continued targeted treatment are lacking. OBJECTIVE: To evaluate long-term outcomes in patients with early RA after 10 years of targeted treatment in 4 treatment strategies. DESIGN: Randomized trial. (Nederlands Trial Register: NTR262 and NTR265). SETTING: The Netherlands. PATIENTS: 508 patients with early active RA. INTERVENTION: Sequential monotherapy (strategy 1), step-up combination therapy (strategy 2), or initial combination therapy with prednisone (strategy 3) or with infliximab (strategy 4), all followed by targeted treatment aiming at low disease activity. MEASUREMENTS: Functional ability (Health Assessment Questionnaire [HAQ] score) and radiographic progression (Sharp-van der Heijde score) were primary end points. Survival in the study population was compared with the general population using the standardized mortality ratio. RESULTS: 195 of 508 of patients (38%) dropped out of the study (28% in strategy 4 vs. 40% to 45% in strategies 1 to 3, respectively). At year 10, mean HAQ score (SD) was 0.57 (0.56); 53% and 14% of patients were in remission and drug-free remission, respectively, without differences among the strategies. Over 10 years, mean HAQ scores were 0.69, 0.72, 0.64, and 0.58 in strategies 1 to 4, respectively (differences not clinically relevant). Radiographic damage was limited for all strategies, with mean Sharp-van der Heijde estimates during follow-up of 11, 8, 8, and 6 in strategies 1 to 4, respectively (P = 0.15). Standardized mortality ratio was 1.16 (95% CI, 0.92 to 1.46) based on 72 observed and 62 expected deaths, with similar survival among the 4 strategies (P = 0.81). LIMITATION: Dropout rate varied by strategy. CONCLUSION: In patients with early RA, initial (temporary) combination therapy results in faster clinical improvement and targeted treatment determines long-term outcomes. Drug-free remission, with prevention of functional deterioration and clinically relevant radiographic damage, and normalized survival are realistic outcomes. PRIMARY FUNDING SOURCE: Dutch College of Health Insurance Companies, Schering-Plough, and Janssen.

Incidence of and Reasons and Determinants Associated with Retransitioning from Biosimilar Etanercept to Originator Etanercept.

BACKGROUND: Patients in clinical practice are transitioned from originator etanercept (OR-ETA) to biosimilar etanercept (BS-ETA), but some subsequently retransition. Insights into the incidence of and reasons for retransitioning and the characteristics of these patients could help clinicians successfully introduce biosimilars. OBJECTIVE: Our objective was to assess the incidence of and reasons for retransitioning from BS-ETA to OR-ETA in patients with a rheumatic disease (RD) and to explore the determinants thereof. METHODS: This cohort study included all patients with RD who had transitioned from OR-ETA to BS-ETA in a large hospital in the Netherlands in 2016. The incidence of retransitioning to OR-ETA and the 1-year persistence with BS-ETA were assessed using the Kaplan-Meier estimator. Reasons for retransitioning were classified as related to (1) efficacy, (2) adverse events, (3) the administration device, and (4) other. Determinants for retransitioning, including baseline and treatment characteristics, were assessed in a nested case-control study using conditional logistic regression. RESULTS: We included 342 patients (median age 57.8 years; 53.5% females). At 1 year after transitioning, 9.4% of patients had retransitioned to OR-ETA and 69.7% were persistent with BS-ETA. At the end of follow-up (median 4.4 years), 47 patients (13.7%) had retransitioned to OR-ETA. The median time until retransitioning was 0.55 years (interquartile range 0.2-1.3). Most patients (n = 34 [72.3%]) retransitioned because of a (perceived) loss of effect, followed by adverse events (23.4%). In total 3.8% of patients switched to another biological treatment or a Janus kinase inhibitor; 17.1% of patients discontinued BS-ETA without retransitioning or switching within the first year. Univariate determinants for retransitioning included initiating corticosteroids or intensifying immunomodulator treatment (odds ratio [OR] 2.37; 95% confidence interval [CI] 1.03-5.45) and the number of visits to the rheumatology department (OR 2.06; 95% CI 1.55-2.74). In the multivariate analysis, only the number of visits to the rheumatology department remained significantly associated with retransitioning (OR 2.19; 95% CI 1.60-3.01). CONCLUSION: When introducing a biosimilar in clinical care, clinicians should anticipate that one in seven patients will retransition to the originator. A (perceived) loss of effect was the most frequently reported reason for retransitioning. Patients who visited the rheumatology department more frequently had an increased risk of retransitioning, which is likely to be related to patients reporting a loss of effect and to adverse events resulting in more visits to the rheumatology department.

Gender differences in retention rate of tumor necrosis factor alpha inhibitor treatment in ankylosing spondylitis: a retrospective cohort study in daily practice.

AIM: To assess gender differences in ankylosing spondylitis (AS) patients in relation to tumor necrosis factor alpha inhibitor (TNFi) drug survival and occurrence of adverse events in daily practice in a large peripheral hospital. METHOD: Retrospective data were collected from AS patients treated with etanercept, infliximab and adalimumab between January 2004 and January 2014. Kaplan-Meier survival curves were conducted to describe the drug survival and occurrence of adverse events in time. RESULTS: Overall, 122 AS patients (60.7% male) were included over a 10-year time period, with a mean treatment period of 51 months (1-127 months). In total, 21 (17.2%) patients stopped the TNFi, mainly due to inefficacy (52.4%). Female patients showed a significant shorter treatment period compared to males (33.4 vs. 44.9 months). In addition, female patients switched more between TNFi compared to males (26.9% vs. 16.3%) and had a significantly higher risk at developing infections compared to male patients (26% vs.19%). CONCLUSION: Females stayed on the same TNFi for a significantly shorter period compared to males (33.4 vs. 44.9 months) and the most important reason to stop or switch the drug was inefficacy. Moreover, females seemed to be more prone to infections during TNFi treatment than males.

Identifying Trajectories of Pain Severity in Early Symptomatic Knee Osteoarthritis: A 5-year Followup of the Cohort Hip and Cohort Knee (CHECK) Study.

OBJECTIVE: To identify subgroups of pain trajectories in patients with symptomatic knee osteoarthritis (OA), and to explain these different trajectories by patient characteristics, lifestyle, and coping factors, as well as radiographic features. METHODS: Longitudinal data of pain severity (0-10) from 5 years of followup of the CHECK (Cohort Hip and Cohort Knee) study was used. Latent class growth analysis identified homogeneous subgroups with distinct trajectories of pain. Multinomial regression analysis was used to examine different lifestyle and coping characteristics between the trajectories. RESULTS: In longitudinal pain data of 5 years of followup in 705 participants, 3 pain trajectories were identified: marginal, mild, and moderate pain trajectories. Compared with the marginal pain trajectory, the mild and moderate pain trajectories can be characterized by the following baseline variables: body mass index (BMI) > 25, additional hip pain, low education level, using the coping strategy "worrying," and having ≥ 3 comorbidities. Moderate pain trajectory can be supplemented with the Kellgren-Lawrence grading scale grade ≥ 2 radiological change. CONCLUSION: Three trajectories of pain were identified. Participants with a BMI > 25, secondary school as highest education level, having at least 3 comorbidities, additional hip pain, and/or whose coping style is worrying are more likely to develop a moderate or mild pain trajectory compared with those without these characteristics. In the management of knee pain in people with early symptomatic OA, attention should also be given to additional factors such as hip pain, other comorbidities, passive coping strategy, and obesity.

Prognostic factors for the two-year course of activity limitations in early osteoarthritis of the hip and/or knee.

OBJECTIVE: To predict the 2-year course of activity limitations in patients with early knee and/or hip osteoarthritis (OA). METHODS: The Cohort Hip & Cohort Knee (CHECK) study is a prospective followup study. The CHECK cohort, comprising participants (n = 1,002) with early OA-related knee and/or hip symptoms, was followed for 2 years. Participants completed questionnaires and underwent physical, laboratory, and radiographic examination. Regression models were used to examine whether baseline variables predicted the course of activity limitations as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Analyses were performed separately for participants with knee symptoms and participants with hip symptoms. RESULTS: After 2 years of followup, activity limitations slightly decreased. Large between-subject variation was observed in WOMAC change scores. In participants with knee symptoms, young age, non-Western ethnicity, bilateral hip pain, morning stiffness in the knee, high comorbidity count, high body mass index, high bodily pain, poor general health perception, and pain coping strategy were associated with a poor 2-year outcome on activity limitations. In participants with hip symptoms, few activity limitations at baseline, bilateral hip pain, morning stiffness in the knee, high comorbidity count, low active hip flexion, poor general health perception, and pain coping strategy were associated with a poor 2-year outcome on activity limitations. CONCLUSION: After 2 years of followup, large between-subject variation was observed in the course of activity limitations. The course of activity limitations is to some extent already predictable at an early stage of knee and hip OA.