Treatment Decisions In Rheumatoid Arthritis Research Articles

Role of comorbidities on therapeutic persistence of biological agents in rheumatoid arthritis: results from the RECord-linkage On Rheumatic Disease study on administrative healthcare databases

Objectives: This study aimed to evaluate the impact of different comorbidities on thereflecting its safety profile persistence of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), taking advantage of a retrospective analysis of administrative healthcare databases (AHDs). Method: A retrospective observational study was conducted on AHDs of the Lombardy region, Italy (2004–2013). Among RA patients treated with bDMARDs, drug survival was estimated using Cox proportional hazard models [hazard ratio (HR), 95% confidence interval (CI)], crude and adjusted for prespecified confounders (gender, age, disease duration, concomitant use of non-steroidal anti-inflammatory drugs, glucocorticoids, conventional DMARDs, specific bDMARDs), in first-line and subsequent lines of treatment. The role of comorbidities in administration of specific bDMARDs was analysed through multinomial logistic models. Results: The study included 4657 RA patients. In the first-line treatment strategy, the Charlson Comorbidity Index (CCI) (RA excluded) was significantly associated with an increased rate of bDMARD failure (CCI = 1: HR 1.28, 95% CI 1.13–1.46; CCI ≥ 2: HR 1.26, 95% CI 1.03–1.53). Among selected comorbidities, chronic obstructive pulmonary disease (HR 1.38, 95% CI 1.01–1.91), diabetes (HR 1.18, 95% CI 1.01–1.37), and previous-year bacterial infections (HR 1.18, 95% CI 1.07–1.30) were slightly associated with risk of bDMARD failure, while acute myocardial infarction (HR 1.30, 95% CI 0.97–1.75), mild liver disease (HR 1.21, 95% CI 0.91–1.60), and solid tumours (HR 1.19, 95% CI 0.93–1.53) were not. In the following treatment lines, neoplasms were associated with reduced risk of failure (HR 0.64, 95% CI 0.41–0.99). Multiple comorbidities were associated with first-line abatacept and rituximab administration. Conclusions: Comorbidities affect treatment decisions in RA and influence bDMARD failure, and should be considered when analysing the persistence of biological therapy.

The hindi version of mcgill pain questionnaire: A cross-cultural adaptation study in rheumatoid arthritis

Background: Pain assessment plays a major role in guiding treatment decisions in rheumatoid arthritis (RA). The long-form McGill Pain Questionnaire (LF-MPQ) is a valid and reliable tool for multidimensional pain assessment. However, a validated Hindi version of the LF-MPQ is not available for use in India. The objective was to develop an equivalent version of the LF-MPQ in native Hindi language that is cross-culturally adapted to suit Indian patients.Methodology: After acquiring permission from the University Ethics Board, guidelines given by the Mapi Research Trust were followed and LF-MPQ was translated to culturally appropriate Hindi version. After translation, the questionnaire was subjected to testing of clinimetric properties in fifty patients with RA.Results: The Hindi version of the LF-MPQ demonstrated high levels of internal consistency (Cronbach's alpha range: 0.74–0.80) and reliability (intraclass correlation coefficient range: 0.76–0.84). The Hindi version of LF-MPQ also demonstrated moderate construct and concurrent validity when tested with Visual Analog Scale (Pearson r: 0.78) and Disease Activity Score in 28 joints (Pearson r: 0.77), respectively.Conclusion: The Hindi version of the LF-MPQ was found to be reproducible and valid for the assessment of pain in patients with RA.

THU0111 PHYSICIAN’S GLOBAL ASSESSMENT OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS: WHAT DO WE REALLY MEAN?

Background:Physician’s global assessment of disease activity (PhGA) is included in some scores of disease activity and, demonstrably, plays a major role upon treatment decisions in rheumatoid arthritis (RA) [1, 2, 3]. Therefore, understanding the reasons underlying the physician´s assessment is crucial.Objectives:To understand the reasons underlying the physician´s assessment.Methods:Cross-sectional study, including consecutive RA patients followed in a Tertiary Rheumatology Department. Socio-demographic (age and gender) and clinical data were collected through a standardized protocol, including 28 tender (TJ28) and swollen (SJC28) joints count, C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Disease activity Score (DAS28-4v-CRP and DAS28-4v-ESR), PhGA and Patient Global Assessment of disease Activity (PGA) through a Visual Analogic Scale (VAS) 0-100mm, Health Assessment Questionnaire (HAQ), European Quality of Life-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Correlation between PhGA and other continuous variables was evaluated through Pearson´s Correlation Coefficient and variables with p<0.05 in univariate analysis were included in multivariable linear regression (stepwise model).Results:392 RA patients (80.6% female, 65.3±12.6 years) were included. PhGA was weakly correlated with CRP (r=0.23), TJC28 (r=0.35), PGA (r=0.26), HAQ (r=0.31) and EQ5D (r=-0.21). Moderate correlations were observed with SJC28 (r=0.45) and DAS-4V-CRP (r=0.48). In multivariable analysis, SJC28 (β=4.14, 95%CI:3.16-5.12), CRP (β=0.22; 95%CI: 0.02-0.03), HAQ (β=4.46, 95%CI:1.50-7.42) and PGA (β=0.08; 95%CI:0.00-0.16) remained as independent correlates of PhGA (R2=0.27, p<0,05).Conclusion:In this study, PhGA was associated with SJC28, CRP, HAQ and PGA, suggesting that physicians adopt a comprehensive reading of the disease into account. However, a large proportion of the variance of PhGA remains unexplained. Given its driving role in treatment decisions, the need to standardize and better understand PhGA seems to deserve a closer attention.

PHS18 - Long-Term Costs Associated with Anti-Cyclic Citrullinated Peptide Positivity in Patients with Rheumatoid Arthritis

Anti-cyclic citrullinated peptide (anti-CCP) positivity has been suggested to be a strong predictor of joint erosion and potential biomarker for guiding treatment decisions in rheumatoid arthritis (RA). This study aimed to evaluate the association between the anti-CCP positivity and long-term direct healthcare expenditures in newly diagnosed RA patients. A retrospective cohort study was conducted in adult RA patients within a US integrated healthcare delivery system (January 2007 to June 2015). Individuals entered the cohort on their first RA diagnosis date (index), and were followed until death, health plan disenrollment, or study end. Patient demographics, anti-CCP positivity at baseline, and healthcare resource utilization during follow-up were collected. Nationally recognized direct medical costs were assigned to healthcare utilization to calculate healthcare costs in 2015 US Dollars. The long-term cumulative mean differences in costs between anti-CCP positive and negative groups were compared accounting for censoring using inverse probability weighting. A total of 2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years. At baseline, 65.8% patients were anti-CCP positive. Anti-CCP positivity was associated with higher biologic DMARDs prescription (22.4% for anti-CCP(+) vs. 12.7% for anti-CCP(-), p<0.001), and rheumatologist utilization (median rheumatologist visits: 13 for anti-CCP(+) vs. 9 for anti-CCP(-), p<0.001). Total additional burden associated with anti-CCP positivity during the 4 years was $14,089 per person ($61,248 for anti-CCP(+) vs. $47,159 for anti-CCP(-), p<0.001). The annual incremental costs for anti-CCP(+) patients increased over time, from $2,163 during the first year to $5,062 during the fourth year. Most of the increased economic burden associated with anti-CCP positivity was from pharmacy expenditures. In newly diagnosed RA patients, anti-CCP positivity was associated with higher long-term economic burden. These results are consistent with the findings that anti-CCP positivity is associated with a poor prognosis and more destructive course of disease.

Biological agents and respiratory infections: Causative mechanisms and practice management.

Biological agents are increasingly being used to treat patients with immune-mediated inflammatory disease. In Japan, currently approved biological agents for patients with rheumatoid arthritis (RA) include tumor necrosis factor inhibitors, interleukin-6 receptor-blocking monoclonal antibody, and T-cell costimulation inhibitor. Rheumatologists have recognized that safety issues are critical aspects of treatment decisions in RA. Therefore, a wealth of safety data has been gathered from a number of sources, including randomized clinical trials and postmarketing data from large national registries. These data revealed that the most serious adverse events from these drugs are respiratory infections, especially pneumonia, tuberculosis, nontuberculous mycobacteriosis, and Pneumocystis jirovecii pneumonia, and that the most common risk factors associated with these respiratory infections are older age, concomitant corticosteroid use, and underlying respiratory comorbidities. Because of this background, in 2014, the Japanese Respiratory Society published their consensus statement of biological agents and respiratory disorders. This review summarizes this statement and adds recent evidence, especially concerning respiratory infections in RA patients, biological agents and respiratory infections, and practice management of respiratory infections in patients treated with biological agents. To decrease the incidence of infections and reduce mortality, we should know the epidemiology, risk factors, management, and methods of prevention of respiratory infections in patients receiving biological agents.

Safety of biologics in rheumatoid arthritis: data from randomized controlled trials and registries.

Over the past decade, the use of biologics has significantly changed the management of rheumatoid arthritis (RA). Biologics selectively target components of the immune system, resulting in better disease control. However, the growing use of biologics in RA has increased safety concerns among rheumatologists. Randomized controlled trials (RCTs) and registries are the most reliable sources of clinical safety data. Although safety data from RCTs provide certain insights into the clinical safety profile of an agent, strict constraints in study design (eg, exclusion criteria and restrictive treatment protocols) often do not accurately reflect possible safety issues in the use of the agent, either in the clinical setting or over long-term treatment. Registries, on the other hand, are not restrictive regarding patient enrollment, making them more reliable in evaluating long-term safety. A number of registries have been established globally: in Europe, the United States, and Asia. However, the availability of registry data from Eastern Europe is lacking. The notable exceptions so far are registries from the Czech Republic (ATTRA, a registry of patients treated with anti-tumor necrosis factor-alpha drugs) and Serbia (National registry of patients with rheumatoid arthritis in Serbia [NARRAS]). The current report provides an overview of safety data with biologics in RA from RCTs and registries. Availability of regional safety data from Eastern Europe is of great importance to its clinicians for making evidence-based treatment decisions in RA.

FRI0004 Randomization to Patient-Reported RAPID3 versus Physician-Based CDAI Tools for Prediction of Treatment Response and Assessment of Patient-Reported Outcomes in Rheumatoid Arthritis Patients Receiving Certolizumab Pegol: Results from the PREDICT Study

BackgroundGuidelines support regular quantitative disease activity monitoring and early intervention in rheumatoid arthritis (RA), but there is no uniform agreement on the best measurement tool.1,2 While physician-based tools like the...

Assessment of combination therapy responses in early rheumatoid arthritis defined by presence or absence of anti-citrullinated protein antibodies

BackgroundUK guidelines recommend that all patients with early active rheumatoid arthritis are offered combination disease-modifying anti-rheumatic drugs (DMARDs) and short-term corticosteroids. This heterogeneous disease has several subsets; one crucial subdivision is defined by the presence or absence of anti-citrullinated protein antibodies (ACPA). These subsets may differ in their treatment responses. We used data from a published randomised controlled trial to assess whether responses to intensive combination treatments in early rheumatoid arthritis differ by ACPA status. MethodsThe Combination Anti-Rheumatic Drugs in Early Rheumatoid Arthritis trial randomised 467 patients with early active disease to receive: methotrexate, methotrexate plus ciclosporin, methotrexate plus prednisolone, or methotrexate plus ciclosporin plus prednisolone in a factorial-design. Patients were assessed 6-monthly for 2 years. In this secondary analysis we assessed 431 patients with available ACPA status. To minimise multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline to 2 years for each outcome (Larsen score, disease activity score in 28 joints [DAS28], health assessment questionnaire, EuroQol, and physical component and mental component summary scores). When a significant interaction was present, mean changes in outcomes were compared between treatment groups at each time-point using t tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. FindingsOf the 431 rheumatoid arthritis cases, 310 (72%) were ACPA-positive and 121 (28%) were ACPA-negative. Effect of treatment on radiological progression differed according to ACPA status, with a significant interactive effect between ACPA and treatment on Larsen score changes observed (p<0·001, ANOVA). ACPA-positive patients had significant reductions in Larsen score progression with all treatments; no effect was seen in ACPA-negative disease. ACPA-positive patients receiving triple therapy had the greatest benefits compared with those on monotherapy (2-year mean Larsen score increase 3·66 [95% CI 2·27–5·05] vs 9·58 [6·76—12·39]; OR for new erosions 0·32 [0·14–0·72], p=0·003). ACPA-negative patients had negligible radiological progression irrespective of treatment (2-year mean Larsen score increase 1·70 [0·29–3·10] with triple therapy vs 2·72 [1·15–4·29] with monotherapy; 7% developed new erosions). The beneficial effects of high-dose corticosteroids on reducing disease activity and improving physical health were confined to ACPA-positive disease. InterpretationIn our study, combination DMARDs and corticosteroids provided radiological, disease activity, and physical health benefits only to patients with ACPA-positive early rheumatoid arthritis. These findings suggest that ACPA is an important biomarker for guiding treatment decisions in rheumatoid arthritis. They indicate that current guidelines advocating combination DMARDs and corticosteroids in all patients with early active disease might require reconsideration. FundingArthritis Research UK, National Institute for Health Research, NIHR Biomedical Research Centre.

Ultrasound in Rheumatology: Where Are We and Where Are We Going?

ObjectiveTo know rheumatologists’ opinion on the usefulness of ultrasound in diagnostic and therapeutic decision making as applied to rheumatic diseases. Materials and methodsA National survey was sent to all rheumatology units in hospitals with at least 200 beds. The questionnaire included: (a) general data, (b) purpose and most common areas of ultrasound exploration and (c) assessment of the usefulness of ultrasound in routine clinical practice in general and in some rheumatologic diseases. ResultsOne-hundred and sixty-nine out of 234 rheumatology units contacted answered the questionnaire. The utility in routine clinical practice was scored at 7.8 (scale 0–10) and ultrasound was integrated in making diagnostic and therapeutic decisions. Half of the indications (50.9%) were ultrasound related to the process of diagnosis of diseases or treatment decision making (monitoring synovitis 14.6%, guided puncture 11.4%, early detection of joint erosion or synovitis 10.3%, early detection of enthesopathy 5.9%, carpal tunnel syndrome or other peripheral neuropathies 3.4%, detection of uric acid or pyrophosphate deposits 3%, vasculitis 1% and others 1.1%. On a 1–5 Likert, scale most of the answers support the use of ultrasound in clinical practice, especially in diagnostic and therapeutic decision making for detection of subclinical synovitis, erosions and treatment decisions in rheumatoid arthritis, enthesitis diagnosis, crystal diseases, polymyalgia rheumatica and giant cell arteritis. ConclusionsUltrasound is becoming a useful tool integrated into clinical practice and is linked to the decision-making processes in the areas of diagnosis, activity and treatment.

La ecografía en reumatología: dónde estamos y hacia dónde nos dirigimos

ObjectiveTo know rheumatologists’ opinion on the usefulness of ultrasound in diagnostic and therapeutic decision making as applied to rheumatic diseases. Material and methodsA National survey was sent to all rheumatology units in hospitals with at least 200 beds. The questionnaire included: a) general data, b) purpose and most common areas of ultrasound exploration and c) assessment of the usefulness of ultrasound in routine clinical practice in general and in some rheumatologic diseases. ResultsOne-hundred-sixty-nine out of 234 rheumatology units contacted answered the questionnaire. The utility in routine clinical practice was scored at 7.8 (scale 0-10) and ultrasound was integrated in making diagnostic and therapeutic decisions. Half of the indications (50.9%) were ultrasound related to the process of diagnosis of diseases or treatment decision making (monitoring synovitis 14.6%, guided puncture 11.4%, early detection of joint erosion or synovitis 10.3%, early detection of enthesopathy 5.9%, carpal tunnel syndrome or other peripheral neuropathies 3.4%, detection of uric acid or pyrophosphate deposits 3%, vasculitis 1% and others 1.1%. On a 1-5 Likert, scale most of the answers support the use of ultrasound in clinical practice, especially in diagnostic and therapeutic decision making for detection of subclinical synovitis, erosions and treatment decisions in rheumatoid arthritis, enthesitis diagnosis, crystal diseases, polymyalgia rheumatica and giant cell arteritis. ConclusionsUltrasound is becoming a useful tool integrated into clinical practice and is linked to the decision making processes in the areas of diagnosis, activity and treatment.

Effect of Rheumatologist Education on Systematic Measurements and Treatment Decisions in Rheumatoid Arthritis: The Metrix Study

To determine whether an educational intervention could result in changes in physicians' practice behavior. Twenty rheumatologists performed a prospective chart audit of 50 consecutive patients with rheumatoid arthritis (RA) and again after 6 months. Ten were randomized to the educational intervention: monthly Web-based conferences on the value of systematic assessments in RA, recent evidence-based information, practice efficiency, and other topics; this group also read articles on targeting care in RA. The others were randomized to no intervention. One thousand serial RA charts were audited at baseline and 1000 at 6 months, with no between-group differences in patient characteristics: mean disease duration of 10 years; 77% women; 74% rheumatoid factor- positive; mean Disease Activity Score (DAS) 3.7; and 68% taking methotrexate, 14% taking steroids, and 27% taking biologics. At 6 months the intervention group collected more global assessments (patient global 53% preintervention vs 66% postintervention, and MD global 51% vs 60%; p < 0.05) and Health Assessment Questionnaires (37% vs 42%; p > 0.05; p = nonsignificant), whereas controls had no change in outcomes collected. For the intervention group there was a 32% increase in calculable composite scores [such as DAS, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index; p < 0.05] but no change in the controls. There was more targeting to a low disease state. For those with SDAI between 3.3 and 11, the percentage of patients receiving a change in therapy was 66% in the intervention group and 36% in controls (p < 0.05). When DAS was between 2.4 and 3.6, 57% of the intervention group and 38% of controls made changes to treatment (p < 0.05). Small-group learning with feedback from practice audits is an inexpensive way to improve outcomes in RA.

Improving agreement in assessment of synovitis in rheumatoid arthritis

ObjectiveSynovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience. MethodsEighteen rheumatologists from French university rheumatology units participated in three 30minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa. ResultsGlobal agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%. ConclusionConsensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists.

Patients with active rheumatoid arthritis but only few tender and swollen joints: a subgroup with impaired short term outcome

The disease activity score of 28 joints (DAS28) is now commonly used for the guidance of treatment decisions in rheumatoid arthritis (RA). The goal of this work was to determine whether patients with DAS28 > 3.2 but less than 2 swollen and 2 tender joints respond differently to treatment than patients with a higher number of active joints. One hundred and ninety two patients with active RA treated in a rheumatology hospital as in-patients were studied prospectively. At admission (T1), release (T2) and 3 months after release (T3) disease activity (DAS28-CRP at T1 + 2, RADAI at T1 + 3), pain (numeric scale at T1 - 3) and function (FFbH at T1 + 3) were measured. A total of 148 patients had two or more (group 1) and 44 less than 2 swollen and tender joints at admission (group 2) but both groups had similar over all DAS28-scores. The groups significantly differed in their outcome after 3 months: group 1 had a significant better reduction of disease activity, pain and functional deficit (p < 0.001 for the fulfilment of defined response criteria and p < 0.05 for comparison of the mean values for pain and function) in comparison to group 2. Although the numbers were small sub-analysis suggested that the differences might be due to a better response to newly administered DMARD and TNF-alpha-inhibitor therapy in group 1. Active RA patients with less than 2 swollen and 2 tender joints represent a subgroup with lower response to treatment with DMARD or TNF-alpha-inhibitors. This has to be taken into account in the management of these patients.

Natural history and treatment decisions in rheumatoid arthritis revisited

Compliance with RA therapeutic intervention must be viewed within the context of the natural history of the disease with or without drug treatment. Published studies from the 30s to the 80s provide a grim picture: both premature death and marked functional morbidity occur even in population-based analyses. Intervention with drugs appears to have short-term gains with little impact beyond 2 years. The reasons for this apparent paradox are two-fold. (1) our drugs are not as successful as we would like; and (2) clinical trials and long-term outcome studies exaggerate their differences from each other by selection criteria and other methodologic issues. Nevertheless, the picture that is emerging for the 90s is revolutionary. Patients with the worst prognosis are being treated more aggressively earlier in their course, and those that have a favorable prognosis do well without aggressive management and are treated differently. Traditional outcome measures are giving way to others that are more realistic and patient-oriented. The assumption that more (not less) treatment will remedy the situation is being tested. The impact of the success of Methotrexate on this change in philosophy should not be underestimated.