Baseline Health Assessment Questionnaire Score Research Articles

Factors predicting treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis – a systematic review and meta-analysis

The therapeutic response of patients with psoriatic arthritis (PsA) varies greatly and is often unsatisfactory. Accordingly, it is essential to individualise treatment selection to minimise long-term complications. This study aimed to identify factors that might predict treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) in patients with PsA and to outline their potential application using artificial intelligence (AI). Five electronic databases were screened to identify relevant studies. A random-effects meta-analysis was performed for factors that were investigated in at least four studies. Finally, 37 studies with a total of 17,042 patients were included. The most frequently investigated predictors in these studies were sex, age, C-reactive protein (CRP), the Health Assessment Questionnaire (HAQ), BMI, and disease duration. The meta-analysis revealed that male sex (odds ratio (OR) = 2.188, 95% confidence interval (CI) = 1.912–2.503) and higher baseline CRP (1.537, 1.111–2.125) were associated with greater treatment response. Older age (0.982, 0.975–0.99), higher baseline HAQ score (0.483, 0.336–0.696), higher baseline DAPSA score (0.789, 0.663–0.938), and higher baseline tender joint count (TJC) (0.97, 0.945–0.996) were negatively correlated with the response to therapy. The other factors were not statistically significant but might be of clinical importance in the context of a complex AI test battery. Further studies are needed to validate these findings and identify novel factors that could guide personalised treatment decisions for PsA patients, in particular in developing AI applications. In accordance with the latest medical developments, decision-support tools based on supervised learning algorithms have been proposed as a clinical application of these predictors.Key messages• Given the often unsatisfactory and unpredictable therapeutic response in patients with Psoriatic Arthritis (PsA), treatment selection must be highly individualized.• A systematic literature review was conducted to identify the most reliable predictors of treatment response to biologic and targeted synthetic disease-modifying antirheumatic drugs in PsA patients.• The potential integration of these predictors into AI tools for routine clinical practice is discussed.

Time-averaged DAS28 and HAQ predict cardiovascular disease in patients with rheumatoid arthritis: Data from KORONA registry.

To evaluate the predictive role of time-averaged disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ) on cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA). Patients with RA were recruited from 23 tertiary hospitals. Baseline and annual follow-up data of demographic, laboratory, questionnaire, RA-associated parameters, and occurrence of CVD were collected. Patients were divided into three groups according to time-averaged DAS28: 1) remission (<2.6), 2) low (2.6-3.2), 3) moderate (3.2-5.1), and 4) high (>5.1). Kaplan-Meier curves was performed to compare the cumulative probability of CVD. Hazard ratios of each factor on the occurrence of CVD were obtained using Cox regression analyses. A total of 4,034 RA patients with 826 for remission, 938 for low, 2,002 for moderate, and 268 for high time-averaged DAS28 groups were included. Baseline age, disease duration, ESR, CRP, DAS28, and HAQ scores were higher in the high time-averaged DAS28 group. The incidence rate of CVD was 2.86, 2.71, 3.53, and 8.13 events per 1,000 person-years for the remission, low, moderate, and high time-averaged DAS28 groups, respectively. The incidence rate ratio of CVD in the high time-averaged DAS28 group were 3.01 (95% CI 1.20-8.50) when compared to low time-averaged DAS28 group. The cumulative hazard for CVD in the high time-averaged DAS28 group was significantly high (log-rank P<0.01). In multivariate Cox regression analysis, age, high time-averaged DAS28, and time-averaged HAQ>0.5, were positively associated with CVD events in RA patients. In patients with RA, time-averaged DAS28 and HAQ could predict the occurrence of CVD. Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function. Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands’ second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected. Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed. Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Relation Between Fatigue and ACR Response in Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitor Therapy: A Population-based Cohort Study.

The objective of this population-based cohort study was to investigate the association between fatigue with disease activity and drug survival in patients with psoriatic arthritis (PsA) receiving their first tumor necrosis factor inhibitor (TNFi). Data on patient characteristics, disease activity, and drug survival were obtained from the DANBIO database on all patients with PsA from 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry. A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measures (Disease Activity Score in 28 joints based on C-reactive protein), pain, and Health Assessment Questionnaire (HAQ) scores; tender joint counts; comorbidities (Charlson Comorbidity Index ≥ 2); and current smoking status at baseline compared to patients with lower median fatigue scores (P < 0.05). In the upper median fatigue group, fewer patients achieved American College of Rheumatology (ACR) responses and improvements in visual analog scale (VAS) fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month follow-up. Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain, and HAQ scores; more comorbidities; and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate, suggesting heterogeneity between experienced fatigue and joint inflammation.

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

BackgroundUnited Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA.MethodsThe study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register–RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership.ResultsIn total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.ConclusionThere is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.

Simplified disease activity changes in real-world practice: a nationwide observational study of seropositive rheumatoid arthritis patients with moderate-to-high disease activity.

Background/AimsThe objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice.MethodsThis was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed.ResultsA total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission.ConclusionsThere was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis Despite Undergoing Treatment for Inflammation: Results From Three UK Cohorts

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59–79% of cohort participants) and resolving pain (19–27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3–2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6–1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PerspectiveImmunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.

HAQ score is an independent predictor of sustained remission in patients with rheumatoid arthritis.

We assessed potential predictors of sustained remission for 2years according to the Disease Activity Score in 28 joints (DAS28)-CRP in patients with rheumatoid arthritis (RA). We obtained data for 290 RA outpatients, from July 2009 to September 2012. Sociodemographic data and answers to questionnaires were collected in face-to-face interviews. Remission was defined according to DAS28-CRP. Sustained remission was defined as meeting criteria for remission in the annual assessment for twoconsecutive years. Predictive factors of sustained remission according to DAS28-CRP were assessed by univariate and multivariate analyses. Of the 290 RA patients, the baseline remission level, according to DAS28-CRP, was 54.5%. During 2years of follow-up, the sustained remission rate was 24.5%. RA patients who achieved sustained remission, according to DAS28-CRP, were younger, and had a shorter duration of symptoms, longer period of education, higher monthly income, lower Health Assessment Questionnaire (HAQ) score, lower physician global assessment, lower patient global assessment, lower patient pain assessment, and higher EQ-5D at baseline. Multivariate analyses showed that the baseline HAQ score was independently associated with sustained remission for 2years according to DAS28-CRP (OR 0.298, 95% CI 0.115-0.770; p=0.012). A lower HAQ score at baseline was an independent predictor of sustained remission at 2years, according to DAS28-CRP. Thus, HAQ scores could be useful when stratifying patients according to risk for flare-ups in the clinic.

Is Swollen to Tender Joint Count Ratio a New and Useful Clinical Marker for Biologic Drug Response in Rheumatoid Arthritis? Results From a Swedish Cohort

To study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. Patients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 ≤ STR ≤ 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. A total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. STR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.

FRI0064 Obesity is associated with current and future disability in early inflammatory polyarthritis: Results from the norfolk arthritis register (NOAR)

BackgroundFunctional disability, usually measured using the Health Assessment Questionnaire (HAQ), is a key outcome in patients with rheumatoid arthritis (RA). The influence of body mass index (BMI) on disease outcomes...

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

BackgroundStudies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients.ObjectiveTo carry...

Baseline HAQ and SF-36 questionnaire scores cannot predict clinical remission, radiographic progression or the need for biological therapy in a three-year prospective study of a Brazilian early rheumatoid arthritis cohort

This study evaluates prospectively whether baseline scores [Health Assessment Questionnaire (HAQ) and SF-36] can predict clinical and radiographic evolution in a cohort of early rheumatoid arthritis (RA) during a 3-year follow-up. Forty consecutive early RA patients were followed for 3 years, while receiving standardized treatment according to a pre-established protocol. HAQ and SF-36 were administered at the initial evaluation and at 3, 6, 12, 18, 24 and 36 months. Hands and feet radiographs were obtained at the initial evaluation and at 12, 24 and 36 months. Preselected outcomes were the occurrence of radiographic erosions, the achievement of an EULAR remission, low disease activity status and the need for biological therapy. The mean age at onset was 45 years with a 90% female predominance. Erosions were found in 42% of patients at T0 and in 70% after 3 years (P < 0.001). At T0, the proportion of patients in remission, low, moderate or high disease activity was 0, 0, 7.5 and 92.5% and 22.5, 7.5, 32.5 and 37.5%, respectively, at 3 years. The mean baseline HAQ score was 1.89 and 0.77 by the third year (P < 0.0001). Most SF-36 domains showed significant improvement except for general state and vitality. Biological therapy was deemed necessary in 22.5% of patients. The initial HAQ and SF-36 scores were not associated with clinical remission, bone erosions or the need for biological therapy at 36 months. The HAQ and SF-36 scores measured at baseline could not predict at 3 years, the preselected outcomes in a Brazilian cohort.

Effectiveness of Rituximab in Patients with Rheumatoid Arthritis: Observational Study from the British Society for Rheumatology Biologics Register

To assess the effectiveness of rituximab (RTX) in patients with rheumatoid arthritis (RA) in routine clinical practice, and to identify predictors of 6-month response to RTX in patients for whom at least 1 anti-tumor necrosis factor-α (anti-TNF) therapy has failed. The analysis involved 646 patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR) who were starting RTX and were followed for at least 6 months. Change in the 28-joint Disease Activity Score (DAS28), European League Against Rheumatism (EULAR) response, and proportions of patients achieving disease remission were used to assess the clinical response 6 months after starting RTX. Regression analyses were used to identify factors associated with the response in the patients for whom anti-TNF therapy had not worked. The models included baseline demographics, disease characteristics, baseline Health Assessment Questionnaire (HAQ), and drug history including biologic history. The mean DAS28 at baseline was 6.2 (95% CI 6.1, 6.3), which decreased significantly to 4.8 (95% CI 4.7, 4.9) at the 6-month followup. Seventeen percent of the patients were EULAR good responders and 43% were moderate responders. Eight percent of the patients achieved disease remission. Subjects with higher baseline DAS28 score and those with positive rheumatoid factor (RF) status were significantly associated with a decrease in their DAS28 score (improvement), while women and patients with higher baseline HAQ score were less likely to improve. RTX has proven to be effective in routine clinical practice. When anti-TNF therapy fails, response to RTX was influenced by baseline DAS28 score, RF status, baseline HAQ score, and sex.

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 μg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 μg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

Influence of age and sex on functional outcome over time in a cohort of patients with recent‐onset inflammatory polyarthritis: Results from the Norfolk arthritis register

It has been found that women with rheumatoid arthritis (RA) have a poorer prognosis than men. However, the impact of age at symptom onset is unclear. We investigated the relationship between these factors and functional disability in patients with recent-onset inflammatory polyarthritis (IP). A total of 3,666 patients (66% women) were registered with the Norfolk Arthritis Register between 1990 and 2008. Functional disability was assessed using the Health Assessment Questionnaire (HAQ), adjusted for age at HAQ completion. Linear random-effects models were used to examine HAQ score over time, by sex and age at symptom onset (early = age <55 years, late = age 55-74 years, very late = age ≥75 years). Women had higher HAQ scores over time than men (mean difference 0.29; 95% confidence interval [95% CI] 0.25, 0.34). Men with late-onset IP had lower baseline HAQ scores than men with early onset (mean difference -0.14; 95% CI -0.29, -0.001). Women had comparable baseline HAQ scores at all ages of onset. Both sexes showed the greatest rate of disability progression in patients with very late onset. Those with early onset had a steady level of disability over time. Adjustment for treatment received, comorbidities, and RA subgroup analysis produced results that were largely similar to the initial analysis. Female patients have higher HAQ scores than male patients; patients with early symptom onset show the smallest sex difference. Older age at symptom onset is associated with an increasingly steep trajectory of disability progression. The impact of sex on outcome is evident at baseline, whereas the impact of age at symptom onset becomes apparent during long-term followup.

Towards personalized treatment: predictors of short-term HAQ response in recent-onset active rheumatoid arthritis are different from predictors of rapid radiological progression

Objective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors?Methods: Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation.Results: At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles.Conclusion: In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient.

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 μg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 μg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study

ObjectivesTo determine the relapse rate after discontinuing treatment in patients with rheumatoid arthritis (RA) in sustained clinical remission, to identify predictors of a relapse and to evaluate treatment response after...

Association of functional outcome with both personal‐ and area‐level socioeconomic inequalities in patients with inflammatory polyarthritis

ObjectiveTo describe the relationship between baseline area- and person-level social inequalities and functional disability at 3 years in patients with early inflammatory polyarthritis (IP).MethodsA total of 1,393 patients with new-onset IP were recruited and allocated an Index of Multiple Deprivation (IMD) 2004 score based on their area of residence, and a social class based on baseline self-reported occupation. Differences in the Health Assessment Questionnaire (HAQ) score at baseline and 3 years by IMD or social class were tested. The mean 3-year change in HAQ score was compared by IMD and social class, and interactions between these measures examined.ResultsPatients from more deprived areas had poorer 3-year HAQ outcome than those from less deprived areas (P = 0.019, adjusted for baseline HAQ score, age, sex, and symptom duration). The mean difference in HAQ change was most notable between the most deprived (IMD4) and least deprived areas (IMD1) (0.22; 95% confidence interval [95% CI] 0.11, 0.34). There was also a significant difference in HAQ score change between patients of the highest (SCI and II) and lowest social class (SCIV and V) (0.11; 95% CI 0.02, 0.20). For the mean (95% CI) 3-year change in HAQ score, a significant interaction exists between IMD score and social class and their association with HAQ scores (P = 0.001) to modify outcome: IMD1/SC I and II −0.23 (95% CI −0.40, −0.06) versus IMD 4/SC IV and V 0.15 (95% CI −0.05, 0.34).ConclusionPerson- and area-level inequalities combine to modify outcome for rheumatoid arthritis. A person's social circumstance and residential environment have independent effects on outcome and are not just alternative measures of the same exposure.

Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

IntroductionAggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators.MethodsCharts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used.ResultsThe proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02).ConclusionsDiscontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.