Biologic Disease-modifying Antirheumatic Drugs Treatment Research Articles

Biomarker combination predicting imminent relapse after discontinuation of biological drugs in patients with rheumatoid arthritis in remission.

Compared to conventional disease-modifying antirheumatic drugs (DMARDs), biological DMARDs demonstrate superior efficacy but come with higher costs and increased infection risks. The ability to stop and resume biological DMARD treatment while maintaining remission would significantly alleviate these barriers and anxieties. The objective of this study was to identify biomarkers that can predict an imminent relapse, hopefully enabling the timely resumption of biological DMARDs before relapse occurs. Forty patients with rheumatoid arthritis who had been in remission for more than 12 months were included in the study. The patients discontinued their biological DMARD treatment and were monitored monthly for the next 24 months. Out of the 40 patients, 14 (35%) remained in remission at the end of the 24-month period, while 26 (65%) experienced relapses at different time points. Among the relapse cases, 13 patients experienced early relapse within 6 months, and another 13 patients had late relapse between 6 months and 24 months. Seventy-three cytokines in the sera collected longitudinally from the 13 patients with late relapse were measured by multiplex immunoassay. Using cytokines at two time points, immediately after withdrawal and just before relapse, volcano plot and area under the receiver operating characteristic curves (AUC) were drawn to select cytokines that distinguished imminent relapse. Univariate and multivariate logistic regression analyses were used for the imminent relapse prediction model. IL-6, IL-29, MMP-3, and thymic stromal lymphopoietin (TSLP) were selected as potential biomarkers for imminent relapse prediction. All four cytokines were upregulated at imminent relapse time point. Univariate and multivariate logistic regression showed that a combination model with IL-6, MMP-3, and TSLP yielded an AUC of 0.828 as top predictors of imminent relapse. This methodology allows for the prediction of imminent relapse while patients are in remission, potentially enabling the implementation of on- and off-treatments while maintaining remission. It also helps alleviate patient anxiety regarding the high cost and infection risks associated with biological DMARDs, which are the main obstacles to benefiting from their superb efficacy.

Diagnostics and treatment of large vessel vasculitis

Giant cell arteritis (GCA) and Takayasu arteritis (TAK), as the main representatives of large vessel vasculitis, are rheumatological autoimmune disorders associated with inflammatory vessel wall changes in the arterial system that can lead to many types of organ damage. In this review the current scientific evidence on the diagnostics and treatment of large vessel vasculitis is evaluated and discussed. In addition to the medical history and clinical presentation, imaging techniques nowadays represent the core of large vessel vasculitis diagnostics and have largely replaced the histological confirmation of GCA. After the diagnosis, acute treatment with glucocorticoids should be initiated as rapidly as possible but in the long term this should be tapered out or replaced by asteroid-sparing basic treatment. In contrast to GCA with already available options and other biologic disease-modifying antirheumatic drugs (DMARDs) about to be approved, there are still no approved biologic DMARD treatment options available for the less common TAK. In contrast to the substantial progress in imaging diagnostics of large vessel vasculitis and with respect to the treatment of GCA, the much rarer TAK still requires intensive research efforts, especially to improve the treatment situation.

Safety of biological disease-modifying antirheumatic drugs in rheumatoid arthritis

ObjectiveThe aim of this study was to assess the safety of the most frequently used biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in clinical practice. MethodA retrospective longitudinal observational study was performed. Clinical information was obtained from the electronic health records of patients diagnosed and treated for rheumatoid arthritis, who had received at least one biologic disease-modifying antirheumatic drug dispensed between 2001 and 2013 from a third-level Hospital pharmacy. Adverse reactions during biologic disease-modifying antirheumatic drugs treatments were analysed, as well as the reasons for treatment discontinuation. A disproportionality analysis (odds ratio with 95% confidence interval) was performed to compare adverse drug reactions related to different system organ classes, the period between the drug start date and the reaction start date (latency period), and previous knowledge of the adverse reactions. ResultsIn total, 210 patients were included in the analysis (73% women, median age 47 years), with 399 prescriptions for biologic disease-modifying antirheumatic drugs and 1,515 adverse reactions potentially related to them. The increased frequency of adverse reactions for each system organ class related to each biologic disease-modifying antirheumatic drug was as follows: general disorders and administration site disturbances with infliximab (2.3 [1.3-4.0]), infections (1.6 [1.3-2.1]) and immune system reactions with etanercept (4.2 [1.2-14.6]), hepatobiliary disorders with adalimumab (2.1 [1.2-3.6]), ophthalmic adverse reactions (1.9 [1.2-3.1]) and cardiac disorders (2.9 [1.0-8.4]) with rituximab, and blood and lymphatic system disorders with tocilizumab (2.9 [1.8-4.7]) and abatacept (3.0 [1.6-5.8)]. The mean latency period was 5 to 33 months. Most adverse reactions were related to adalimumab (93.6%; P < 0.01), whereas the fewest adverse reactions were related to tocilizumab (55.2%; P < 0.01). Most treatment withdrawals related to adverse reactions were identified during the first year of biologic disease-modifying antirheumatic drugs treatment. ConclusionsTumour necrosis factor a inhibitors were associated with general disorders and administration site disturbances, infections and immune system reactions, and hepatobiliary abormalities, whereas nontumour necrosis factor a inhibitors were associated with cardiac disorders as well as blood and lymphatic system disorders. Treatment withdrawals mainly occurred during the first year of treatment. Most of the adverse reactions have been previously described.

Effect of a 12-week high-intensity exercise intervention: a comparison of cardiac exercise adaptations during biological disease-modifying antirheumatic drug treatment (TNF inhibitors vs IL-6 signalling inhibitors) in patients with rheumatoid arthritis – study protocol for a randomised controlled trial

IntroductionThe chronic inflammatory state in rheumatoid arthritis (RA) augments the risk of cardiovascular disease (CVD), with pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin 6 (IL-6) playing a vital role....

Continue or interrupt? Antirheumatic treatment in elective surgery

In patients with inflammatory rheumatic diseases, adecision is needed prior to elective surgery on whether the medicinal treatment can be continued or whether the dose needs to be changed or interrupted. The German Society for Rheumatology (DGRh) has developed updated recommendations that specify acourse of action for disease-modifying antirheumatic drugs (DMARD) and glucocorticoids. The recommendations for action can be adapted to the individual situation and coordinated with the interdisciplinary treating physicians and the patient. Depending on the dose, glucocorticoids have ahigh risk of infection and should be set as low as possible in the preoperative period. Most of the conventional synthetic (cs)DMARDs can be continued. Under biologic (b)DMARDs treatment surgery can be scheduled for the end of each treatment interval. It is recommended that Janus kinase (JAK) inhibitors should be interrupted for 3-4days before major interventions. Treatment should be restarted as soon as possible, depending on the wound healing.

A Single-Center Retrospective Observational Study Evaluating the Favorable Predictive Factors for the Disease Control Time of Treatment with Tocilizumab in Patients of Rheumatoid Arthritis

BackgroundTocilizumab (TCZ) is humanized monoclonal antibody against the interleukin-6 (IL-6) and receptor that has prominent efficacy for the treatment of rheumatoid arthritis (RA). We conducted a retrospective observational study to determine how long TCZ controls RA.Patients and MethodsWe retrospectively reviewed the medical records of RA patients treated with TCZ. The aim of this study was to evaluate the contribution of clinical parameters to disease control time (DCT) in RA patients.ResultsOverall, 144 patients were enrolled in the study. The median age of patients was 66 years (range: 34–85 years). In univariate analysis, DCT was significantly increased in patients who had never received previous biologic disease-modifying anti-rheumatic drugs treatment (P = 0.0064). We also analyzed the contribution of the base line value of C-reactive protein (CRP) to DCT. We divided the patients with RA into two groups according to a cutoff value of 1.000 mg/dl. The median control times were 77.5 months (95% confidence interval [CI]: 44.8–not reached to median) and 34.5 months (95% CI: 17.0–79.3) for patients with high and low CRP value, respectively. In univariate analysis, DCT was significantly increased in patients with a high CRP value (P = 0.0283). Multivariate analysis clearly revealed that a high baseline CRP value was an independent favorable predictive factor for longer DCT (hazard ratio, 0.608, 95% CI: 0.378–0.981, P = 0.0416).ConclusionThese data clearly demonstrate that the baseline value of CRP was closely associated with long time DCT in patients of RA treated with TCZ.

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

ObjectiveTo compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic...

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

BackgroundHepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg−/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs).MethodsUsing a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg−/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs− serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one-to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses.ResultsAmong 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ~ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89–0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48–15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22–88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88–0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39–871.5).ConclusionsBesides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg−/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Safety and Effectiveness of Biologic Disease-Modifying Antirheumatic Drugs in Older Patients with Rheumatoid Arthritis: A Prospective Cohort Study.

The number of older patients with rheumatoid arthritis is increasing, but data on drug effectiveness and safety in these patients are scarce. This study assessed the effectiveness and safety of biologic disease-modifying antirheumatic drugs in older patients with rheumatoid arthritis. This prospective cohort study was based on data recorded in the Rheumatic Diseases Portuguese Register (Reuma.pt). Treatment persistence, European League Against Rheumatism response at 6 and 12months, and adverse events were compared between adult (age < 65years), old (age 65-74years), and very old (age ≥ 75years) patients. In total, 2401 patients were included, of which 379 were old and 83 were very old. Older patients had higher disease activity at baseline (Disease Activity Score 28: 5.5 in adults, 5.7 in old patients, and 6 in very old patients; p = 0.02) and more comorbidities, with patients aged 65-74years beginning biologic disease-modifying antirheumatic drugs later in the course of rheumatoid arthritis. Treatment persistence was similar in the three patient groups (p = 0.07). The European League Against Rheumatism response rates were comparable in the three groups at 6months (81.6% of adults, 75.2% of old patients, and 81.8% of very old patients; p = 0.19), and inferior in old patients at 12months. The proportion of patients who experienced adverse events was also similar in the three groups (21% of adults, 22.5% of old patients, and 22.9% of very old patients; p = 0.76), but the rate of serious adverse events was higher in old patients (1.94/100 patient-years) and very old patients (4.29/100 patient-years) compared with 1.03/100 patient-years in adult patients with rheumatoid arthritis (p < 0.05). Adults, old patients, and very old patients with rheumatoid arthritis benefit similarly from biologic disease-modifying antirheumatic drug treatments, although older patients have more active disease at baseline and more comorbidities. However, it is necessary to consider the risk of serious adverse events in older patients when prescribing a biologic.

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High-Risk Lesions.

To evaluate whether biologic disease-modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression. In this single-center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low-attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham-D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. After adjustment for the segment stenosis score, the Framingham-D'Agostino score, and time-varying Disease Activity Score in 28 joints using the C-reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long-term CVD risk (OR 0.15 [95% CI 0.04-0.60]). Noncalcified and low-attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low-attenuation plaque at baseline (OR 0.21 [95% CI 0.04-0.99] and OR 0.08 [95% CI 0.01-0.70], respectively), but not in those without noncalcified or low-attenuation plaque. Per-segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05-15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17-0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low-attenuation plaque loss (P = 0.042). Our findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis.

Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in patients with rheumatoid arthritis treated with synthetic drugs, in clinical remission by DAS28

ObjectiveTo identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). MethodsThis is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. ResultsPatients’ mean age was 49.1±13.7 years; 83% were women. The mean disease duration was 8±7 years and remission lasted for 27.5±31.8 months. The mean DAS28 score was 1.9±0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI 95%, 0.34–0.81) and 0.81, p<0.0001 (CI 95%, 0.27–0.83) respectively. ConclusionsLow percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity.

Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: ASystematic Review.

Randomized controlled trials (RCTs) exist along a spectrum, from explanatory, designed to evaluate interventions under ideal conditions, to pragmatic, designed to reflect usual care. This study assessed the pragmatism of RCTs of advanced therapeutics in rheumatoid arthritis (RA). A systematic review was conducted to identify RA RCTs comparing biologic or targeted synthetic therapy in combination with methotrexate, to placebo or any other disease-modifying antirheumatic drugs (DMARDs). Trials were rated using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool in 9 domains, each rated from 1 (very explanatory) to 5 (very pragmatic). Latent class and regression analyses examined the heterogeneity in PRECIS-2 scores and the relationship to trial characteristics. In total, 96 trials were included. Eligibility, follow-up, and flexibility of delivery of the intervention were rated as explanatory, with mean ± SD PRECIS-2 scores of 2.0 ± 0.7, 2.0 ± 1.1, and 2.1 ± 0.7, respectively, reflecting strict inclusion criteria, intensive follow-up, and rigid protocols. Studies were rated as pragmatic in setting (3.6 ± 1.5) because many were international, multicenter trials, and in primary analysis (4.1 ± 1.3), because most used intent-to-treat analyses. In latent class analyses, 2 groups were identified; the majority (74%) were rated as explanatory for most domains assessed. These trials had larger sample sizes, were more likely to be industry-funded, and enrolled patients with higher Disease Activity Score in 28 joints and Health Assessment Questionnaire disability index scores, but were less likely to be at high risk of bias. RCTs of biologic DMARD treatment in combination with methotrexate for RA were rated as predominantly explanatory, which may affect the generalizability of trial results to clinical practice.

Biologic Disease-Modifying Antirheumatic Drugs and Risk of Multiple Myeloma

INTRODUCTIONBiologic disease-modifying antirheumatic drugs (DMARDs) are used more frequently and earlier in the course of rheumatologic conditions in a treat-to-target approach. These medications act on proteins and cytokines with potential pro- and anti-malignancy roles, including tumor necrosis factor-alpha (TNF), human interleukin (IL) receptors and B- and T-cell functions. There is concern for hematologic malignancy with some but not all biologic DMARDs. Little is known about possible associations between these medications and development of multiple myeloma (MM). Our purpose was to determine risk of MM in relation to biologic DMARD treatment, duration of use and by biologic target in a large cohort of patients with rheumatologic conditions. METHODSWe conducted a nested case-control study within a cohort of adults undergoing active treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Patients were sampled from a population of commercially-insured U.S. health plan enrollees in the Truven Health MarketScan Research Database between 2009 and 2015. MM cases were ascertained using validated algorithms for administrative data. Up to ten controls from the overall cohort were matched to each MM case on age, sex and rheumatologic indication using incidence density sampling with replacement. Index date was defined as the date of MM diagnosis for a case and corresponding time at-risk for matched controls. Exposure was defined as both treatment and duration of biologic DMARD use including TNF inhibitor (etanercept, infliximab, adalimumab, golimumab, certolizumab pegol), IL-6 receptor antagonist (tocilizumab), T-cell targeted (abatacept) and B-cell depleting (rituximab) agents and were determined from health claims and pharmacy dispensing data. Data on rheumatologic indication, comorbid conditions and treatment with prescription nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and conventional synthetic DMARDs (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) were documented in the 12 month baseline period and during follow up as potential confounders. An exposure lag time of 365 days was used to minimize protopathic bias. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of MM associated with biologic DMARDs. RESULTSFrom a retrospective cohort of 56866 adult patients with rheumatologic conditions, 287 MM cases and 2760 matched controls were identified. Compared to controls, a higher proportion of cases had Charlson comorbidity scores of 2 or greater (24% vs 18%) and used oral corticosteroids during follow up (67% vs 61%). Cases and controls were similar with respect to use of prescription NSAIDs (56% vs 59%) and use of conventional DMARDs (63% vs 67%). Use of biologic DMARDs overall was similar between cases and controls (14% vs 15%), although cases had a slightly lower proportion of etanercept users (5% vs 7%) and a slightly higher proportion of tocilizumab users (1.4% vs 0.4%). Biologic DMARD users were younger, more likely to have psoriatic arthritis or ankylosing spondylitis, lower comorbidity and greater use of concomitant NSAIDs and oral corticosteroids.Risk of MM was neither associated with biologic DMARD use overall (OR 0.84; 95% CI 0.57, 1.26; P=0.40) nor with longer duration of biologic DMARD use (>2.5 years: OR 0.72; 95% CI 0.34, 1.52; P=0.39). However, compared to patients treated with only conventional DMARDs, those receiving concomitant conventional plus biologic DMARDs had a 48% lower risk of developing MM (OR 0.52; 95% CI 0.30, 0.88; P=0.02). Associations with MM appeared to differ by specific biologic DMARD agent with estimates suggesting a lowered risk of MM with use of etanercept (OR 0.55; 95% CI 0.30, 1.02; P=0.06) and greater risk with use of tocilizumab (OR 4.33; 95% CI 1.33, 14.19; P=0.02) that was statistically significant, although confidence intervals were wide. CONCLUSIONSThe potential influence of biologic DMARDs on multiple myeloma is complex. We found that immune suppression with conventional plus biologic DMARDs is inversely associated with MM risk in patients with rheumatologic conditions, but this association differed by biologic drug target. Further research is needed to understand the roles of DMARDs targeting TNF and IL-6 in relation to subsequent myeloma pathogenesis. DisclosuresPatel:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still’s disease

ObjectivesAdult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant...

Factors associated with initial or subsequent choice of biologic disease-modifying antirheumatic drugs for treatment of rheumatoid arthritis

BackgroundBiologic disease-modifying antirheumatic drugs (DMARDs) are increasingly used for rheumatoid arthritis (RA) treatment. However, little is known based on contemporary data about the factors associated with DMARDs and patterns of use of biologic DMARDs for initial and subsequent RA treatment.MethodsWe conducted an observational cohort study using claims data from a commercial health plan (2004–2013) and Medicaid (2000–2010) in three study groups: patients with early untreated RA who were naïve to any type of DMARD and patients with prevalent RA with or without prior exposure to one biologic DMARD. Multivariable logistic regression models were used to examine the effect of patient demographics, clinical characteristics and healthcare utilization factors on the initial and subsequent choice of biologic DMARDs for RA.ResultsWe identified a total of 195,433 RA patients including 78,667 (40%) with early untreated RA and 93,534 (48%) and 23,232 (12%) with prevalent RA, without or with prior biologic DMARD treatment, respectively. Patients in the commercial insurance were 87% more likely to initiate a biologic DMARD versus patients in Medicaid (OR = 1.87, 95% CI = 1.70–2.05). In Medicaid, African-Americans had lower odds of initiating (OR = 0.59, 95% CI = 0.51–0.68 in early untreated RA; OR = 0.71, 95% CI = 0.61–0.74 in prevalent RA) and switching (OR = 0.71, 95% CI = 0.55–0.90) biologic DMARDs than non-Hispanic whites. Prior use of steroid and non-biologic DMARDs predicted both biologic DMARD initiation and subsequent switching. Etanercept, adalimumab, and infliximab were the most commonly used first-line and second-line biologic DMARDS; patients on anakinra and golimumab were most likely to be switched to other biologic DMARDS.ConclusionsInsurance type, race, and previous use of steroids and non-biologic DMARDs were strongly associated with initial or subsequent treatment with biologic DMARDs.

Relationship between clinical evaluation and ultrasound assessment of rheumatoid arthritis patients using a 12 joint score

To identify if the use of a systematic ultrasound (US) evaluation has relevance in the determination of disease activity in rheumatoid arthritis patients on biological disease-modifying anti-rheumatic drug treatment. A 12 joint US assessment was performed on the same day of the routine clinical examination. Both Grey-scale (GS) and Power Doppler (PD) were graded semi-quantitatively (0-3 scale). Forty-one patients were included. GS or PD > 0 were found in 24% and 3% of the ankles, 21% and 17% of the wrists, 19% and 9% of the second metacarpophalangeal joints (MCP), 7% and 2% of the third MCP, 6% and 0% of the knees and 5% and 0% of the elbows, respectively; tenosynovitis of the tibialis posterior was found in 19% of the ankles. Eight of the patients with Disease Activity Score of 28 joints (DAS28) ≤ 2.6 (n = 15) had an US score of 0. Twenty-seven joints (6.7%) had US evidence of synovitis but were not considered to be swollen; 10 (2.5%) were considered to be swollen but had no US evidence of synovitis. Using a 12 joint US assessment, a high proportion of patients with DAS28 < 2.6 were found to have inflammatory US activity, and a significant proportion of patients had evidence of tenosynovitis of the tibialis posterior, which may be difficult to clinically detect. A regular and standardized US assessment of RA patients is therefore warranted to complement clinical evaluation and better define disease activity.

Impact of Out-of-Pocket Costs on Prescription Fills Among New Initiators of Biologic Therapies for Rheumatoid Arthritis.

Biologic disease-modifying antirheumatic drug (DMARD) therapies are a mainstay of treatment for rheumatoid arthritis (RA), yet high member out-of-pocket (OOP) costs for such therapies may limit patient access to these therapies. To understand whether there is a relationship between OOP costs and the initial fill and subsequent refills of biologic DMARD treatments for RA members. Members of a national Medicare Advantage and Prescription Drug (MAPD) plan with an adjudicated (paid or reversed) claim for a biologic DMARD indicated for RA were identified from July 1, 2007, to December 31, 2012, and followed retrospectively. The first adjudicated claim date was the index date. Members were required to have 180 days of continuous enrollment pre- and post-index and ≥ 1 diagnosis for RA (ICD-9-CM: 714.0 or 714.2) during pre-index or ≤ 30 days post-index. Low-income subsidy and Medicaid-Medicare dual-eligible patients were excluded. The analysis used multivariate regression models to examine associations between initial prescription (Rx) abandonment rates and OOP costs and factors influencing the refill of a biologic DMARD therapy based on pharmacy claims. The final sample size included 864 MAPD members with an adjudicated claim for a biologic DMARD. The majority were female (77.4%) and mean age was 63.5 years (SD = 10.9). Most (78%) had conventional nonbiologic DMARD utilization during pre-index. The overall initial abandonment rate was 18.2% for biologic DMARDs, ranging from 1.3% for the lowest OOP cost group ($0-$250) to 32.7% for the highest OOP cost group (> $550; P < 0.0001 for Cochran-Armitage trend test). ORs for abandonment rose from 18.4 to 32.7 to 41.2 for OOP costs of $250.01-$400.00, $400.01-$550.00, and > $550.00 respectively, relative to OOP costs of ≤ $250.00 (all P < 0.0001). Meeting the catastrophic coverage limit and utilization of a specialty pharmacy for the index claim were both associated with a decreased likelihood of abandoning therapy (OR = 0.29 and OR = 0.14, respectively; both P < 0.05). Among the subset of 533 members with a paid claim, 82.4% had at least 1 refill post-index. The negative association between OOP cost and likelihood of refilling an Rx was highly significant (P < 0.0001). This study suggests that the higher the member OOP cost, the less likely an MAPD member is to initiate or refill a biologic DMARD therapy for RA. Further research is needed to understand reasons for initial Rx abandonment and lack of refills, including benefit design and adverse events.

Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study

ObjectiveTo prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised...

FRI0054 Left Ventricular Function and Structure in Patients with Rheumatoid Arthritis without Cardiac Symptoms: Comparison between Nonbiologic and Biologic DMARD Treatment Groups

BackgroundCongestive heart failure (CHF) is a major contributor to morbidity and mortality in rheumatoid arthritis (RA) patients, but effects of disease-modifying antirheumatic drugs (DMARDs) on myocardial structure and function are...

AB0079 Synovial Explant Inflammatory Mediator Production is Correlated with Disease Activity in Rheumatoid Arthritis: A Cross Sectional Study

BackgroundIn vitro assays are widely used for characterisation of rheumatoid arthritis (RA) pathology and for testing of potential disease modifying anti-rheumatic drugs (DMARDs). However, little is known to what extent...