Disease-modifying Antirheumatic Drugs In Rheumatoid Arthritis Patients Research Articles

P122 Secular trends in prescription of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis: Experience from a UK regional centre (2016-2022)

Abstract Background/Aims In the past two decades, biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) have substantially transformed the treatment landscape for rheumatoid arthritis (RA). With the emergence of new molecules, the introduction of cost-effective biosimilars, and the impact of the COVID pandemic, the treatment preferences might have shifted over time. We aim to explore the evolving trends in the prescription of biologic and targeted synthetic DMARDs in RA patients whose disease was refractory to conventional DMARDs. Methods A biologic registry was set up sourcing data from pharmacy and departmental records. Data of RA patients who were commenced on biologics or targeted synthetic DMARDs between January 2016 and December 2022 are presented descriptively without formal statistical assessments. Line plots depict prescription trends over the years. Data visualization done using R studio (v 2023.06). Results We have 1504 out of the 2345 patients in our biologic registry with RA; 827 of these patients commenced the treatment in the 7-year study period. Over the years, biosimilars are increasingly being preferred as the first-line agents. If a biosimilar for a biologic drug was available, all prescriptions were for the biosimilar in 2022. There was a significant drop (43.7%) in biologic prescriptions during the pandemic in 2020 compared to the previous year. However, by the next year, prescriptions rebounded to 91% of their pre-pandemic levels. TNF inhibitors and Janus kinase (JAK) inhibitors were the most common treatments initiated. There was a steady increase in the prescription of JAK inhibitors since their introduction in 2017. During the pandemic, JAK inhibitors were the most preferred agents for RA. However, a decline in their prescriptions was noted in 2022, down 36% from the previous year, possibly due to emerging concerns about their cardiovascular safety. While there was reduction in prescription of all biologics during pandemic, anti B cell therapy had the steepest decline (74.1% reduction in 2020 compared to previous year). This may be due to the increased risk of SARS-CoV-2 infection and impaired response to the vaccine with Rituximab. This trend is gradually reversing. Rates of prescription of abatacept and anti-IL6 agents remained fairly stable across the seven years. Conclusion Significant fluctuations are evident in the trend of prescription of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in a regional centre in UK. We conclude that availability of biosimilars, safety data on JAK inhibitors and impact of the COVID pandemic had influenced the prescription trends. Disclosure H. Muhammed: None. H. Osborn: None. K. Hughes: None. A. Yau: None. G. Hirsch: None. S. Raizada: None. T. Sheeran: None. S. Venkatachalam: None.

Factors influencing prescribing the first add-on disease-modifying antirheumatic drugs in patients initiating methotrexate for rheumatoid arthritis

BackgroundAdvances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX. MethodsThis retrospective cohort study utilized the MarketScan data (2012–2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with continuous enrollment for the 6-month pre-index period. The combination therapy users received the first treatment addition of DMARD starting from day 30 after the index MTX over one year period. The study focused on the addition of csDMARDs, Tumor Necrosis Factor Inhibitors (TNFi) bDMARDs, non-TNFi bDMARDs, or tsDMARDs. Baseline covariates were measured in the 6-month pre-index and grouped into predisposing, enabling, and need factors, as per the Andersen Behavior Model. Multivariable logistic regression examined the factors associated with the addition of TNFi compared to adding a csDMARD. An additional regression model evaluated the factors associated with adding any biologic (combining TNFi and non-TNFi biologics). ResultsAmong 8350 RA patients starting MTX, 31.92% (n = 2665) initiated any DMARD within the 1-year post-index period. Among RA patients initiating a DMARD prescription after starting MTX, 945 (11.32%) received combination therapy with treatment addition of a DMARD to MTX regimen; majority added TNFi (550, 58%), followed by csDMARD (352, 37%); non-TNF biologic (40, 4%), or tsDMARD (3, 0.3%). The tsDMARD group was limited and was not included for further analysis. The multivariable model found Preferred Provider Organization insurance coverage (odds ratio [OR], 1.43; 95% confidence interval (CI), 1.06–1.93), chronic pulmonary disease (OR, 1.98; 95% CI, 1.14–3.44), liver disease (OR, 5.24; 95% CI, 1.77–15.49), and Elixhauser score (OR, 0.91; 95% CI, 0.86–0.97) were significantly associated with the addition of TNF-α inhibitors. The separate multivariable model additionally found that patients from metropolitan areas (OR, 1.50; 95% CI, 1.04–2.16) were positively associated with adding any biological agent. ConclusionsTNFi are often added to MTX for managing RA. Enabling and need factors contribute to the prescribing of a TNFi add-on therapy in RA. Future research should examine the impact of these combination therapies on RA management.

Physical Function of RA patients Tapering Treatment-A Post Hoc Analysis of the Randomized Controlled RETRO Trial.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.

The Clinical Utility of Musculoskeletal Ultrasound for Disease Activity Evaluation and Therapeutic Response Prediction in Rheumatoid Arthritis Patients: A Narrative Review.

Rheumatoid arthritis (RA) is characterized by persistent synovitis and joint/bone destruction. There is an unmet need to predict the therapeutic response to disease-modifying anti-rheumatic drugs (DMARDs) and achieve a treat-to-target goal. Musculoskeletal ultrasound (MSUS) is widely used to identify structural change and assess therapeutic response in RA. This review aims to summarize the available evidence regarding the clinical application of MSUS in evaluating disease activity and predicting therapeutic responses to DMARDs. We searched the MEDLINE database using the PubMed interface and reviewed English-language literature from 2000 to 2022. This review focuses on the updated role of MSUS in assessing disease activity and predicting therapeutic responses to DMARDs in RA patients. MSUS is now widely applied to identify articular structural change and assess the disease activity of RA. Combined use of gray scale and power Doppler MSUS is also superior to clinical assessment and laboratory examination in evaluating disease activity of RA. With portable use, good viability, and high sensitivity to articular inflammation, MSUS would be useful in assessing therapeutic response to biologic/targeted synthetic DMARDs (b/tsDMARDs) in RA patients. Given MSUS could also detect subclinical inflammation in a substantial proportion of RA patients with clinical remission, it is recommended to assess b/tsDMARDs-treated RA patients who have achieved low disease activity or remission. Although substantial literature data have revealed clinical utility of MSUS for monitoring disease activity and evaluating therapeutic response in RA patients, the evidence regarding its predictive value for the effectiveness of b/tsDMARDs is limited.

Associations between the interleukin-6 rs1800795 G/C and interleukin-6 receptor rs12083537 A/G polymorphisms and response to disease-modifying antirheumatic drugs in rheumatoid arthritis: A meta-analysis

ObjectiveWe aimed to investigate the association between interleukin-6 (IL-6) rs1800795 G/C, IL-6 receptor (IL-6R) rs12083537 A/G, and rs4329505 T/C polymorphisms and responsiveness to disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). MethodsWe searched Medline, Embase, and Web of Science databases. We conducted a meta-analysis of studies on the association between the IL-6 rs1800795 G/C, IL-6R rs12083537 A/G and rs4329505 T/C polymorphisms and responsiveness to DMARDs in RA patients. ResultsFourteen studies from eight published articles involving 982 patients were included in this meta-analysis. The meta-analysis showed a significant association between the IL-6 rs1800795 G allele and response to DMARDs in RA (P = 0.008). Stratification by DMARD class showed that the IL-6 rs1800795 G allele was significantly associated with responsiveness to biological DMARDs (bDMARDs) (P = 0.022), but not conventional synthetic DMARDs (P = 0.145). A significant association was also found between the IL-6 rs1800795 G/C polymorphism and response to DMARDs. The meta-analysis revealed a significant association between the IL-6R rs12083537 A allele and response to tocilizumab in RA patients (P = 0.001). A significant association was also found between the IL-6R rs12083537 AA genotype and response to tocilizumab in RA patients (P = 0.001). However, no association was found between the IL-6R rs4329505 T/C polymorphism and response to tocilizumab. ConclusionsThis meta-analysis revealed associations between treatment response to bDMARDs and the IL-6 rs1800795 G/C polymorphism, and between response to tocilizumab and the IL-6R rs12083537 A/G polymorphism in RA.

AB0414 DRUG PERSISTENCE ON JANUS KINASE (JAK) INHIBITORS COMPARED TO BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS: RETROSPECTIVE STUDY IN THE AUSTRALIAN POPULATION

BackgroundIn rheumatoid arthritis (RA) persistence on disease modifying anti-rheumatic drugs (DMARDs) can be interpreted as a composite measure of effectiveness, safety, and tolerability. There is limited data available on real-life use of the newest class of drugs, the Janus Kinase (JAK) inhibitors. JAK inhibitors are small-molecule treatments which are administered orally on a daily basis and offer a long-term option in RA treatment.ObjectivesTo compare drug persistence on JAK inhibitors tofacitinib, baricitinib and upadacitinib to tumor necrosis factor-α (TNF) inhibitors and other DMARDs in RA patients in Australia.MethodsA retrospective observational study was conducted among RA patients in the Australian Medicare Database (from January 2006 till October 2021), aged ≥18 and for whom a JAK inhibitor or biologic DMARDs were dispensed. Data were provided by the Australian Department of Health and Aging through PROSPECTION, an Australian healthcare consulting company. A deidentified 10% sample of the database was taken as a random representation of RA patients in Australia.Kaplan-Meier analysis was used to calculate drug persistence rates, defined as the time from treatment initiation until the date of the last dose when there had not been a script dispensed for 6 months; except for rituximab, where a 12-month gap was applied.ResultsData from 5,455 patients were analysed. For all patients the 12-month persistence rates were 61% for JAK inhibitors (baricitinib, tofacitinib, upadacitinib), 62% for tocilizumab, 52% for TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), and 51% for abatacept. The JAK inhibitors baricitinib (64%) and upadacitinib (78%) were superior to tofacitinib (54%). Median treatment persistence for upadacitinib was not reached (n = 430); was 27.1 months for baricitinib and 15.2 months for tofacitinib. For TNF inhibitors, treatment persistence was 15.1 months for adalimumab, 14.1 months for certolizumab, 14.0 months for etanercept, 11.1 months for golimumab and 4.5 months for infliximab.Persistence rates on first-line JAK inhibitors were 70% for baricitinib and 57% for tofacitinib; persistence rates dropped to 63% for baricitinib and 47% for tofacitinib in the second-line setting. First-line persistence rates were 54% for TNF inhibitors and 65% for tocilizumab, rates were sustained for tocilizumab, but dropped to 48% for TNF inhibitors in the second-line setting.ConclusionThis real-world data highlights that in an Australian clinical practice setting treatment persistence rates on 12 months on JAK inhibitors, in particular baricitinib and upadacitinib, were superior to TNF inhibitors, but not to tocilizumab. Suggesting that persistence rates might differ according to biologics mode of action and line of treatment.Table 1.Persistence rates at 12 months post treatment initiationAll patientsFirst lineSecond lineJAK inhibitorsOverall61% (2155)60% (616)60% (554)Baricitinib64% (537)70% (158)63% (124)Tofacitinib54% (1188)57% (441)47% (294)Upadacitinib78% (430)28% (17)84% (136)TNF inhibitorsOverall52% (6339)54% (4227)48% (1561)Adalimumab55% (2710)56% (2030)48% (590)Certolizumab51% (593)54% (251)47% (147)Etanercept52% (2079)55% (1354)47% (623)Golimumab49% (814)49% (506)47% (174)Infliximab35% (143)23% (86)53% (27)Other DMARDsAbatacept51% (952)56% (263)46% (310)Rituximab49% (284)41% (70)65% (79)Tocilizumab62% (1156)65% (279)65% (351)In brackets are number of patients.

Frequency of real-world reported adverse drug reactions in rheumatoid arthritis patients

ABSTRACT Objectives To describe the cumulative incidences of adverse drug reactions (ADRs) associated with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients from real-world data (RWD), using the DREAM-RA registry, and to compare these with incidence frequencies mentioned in the Summary of Product Characteristics (SmPC). Methods All ADRs in patients with recorded use of adalimumab, etanercept, hydroxychloroquine, leflunomide, oral and subcutaneous methotrexate, and sulfasalazine from a single center participating in the DREAM-RA registry (n = 1,098 patients) that were directly sent to the Netherlands Pharmacovigilance Center Lareb were assessed. Cumulative incidences were calculated, described and compared to the most recently revised SmPCs. Results In total, 14 ADRs (≥5 case reports) associated with the use of one of the included DMARDs were reported with a higher estimated cumulative incidence compared to the SmPC. For hydroxychloroquine and sulfasalazine, 5 ADRs (≥5 case reports) mentioned with an ‘unknown’ incidence in the SmPC were reported as ‘common’ in this study. Conclusions Although ADR data in the DREAM-RA registry were partly comparable with data in the SmPCs, RWD from this patient registry provided an added value to the currently available information on the incidences of ADRs associated with DMARDs in RA patients as described in SmPCs.

DMARD-free remission as novel treatment target in rheumatoid arthritis: A systematic literature review of achievability and sustainability

ObjectivesAlthough current treatment guidelines for rheumatoid arthritis (RA) suggest tapering disease-modifying anti-rheumatic drugs (DMARDs), it is unclear whether DMARD-free remission (DFR) is an achievable and sustainable outcome. Therefore, we systematically...

Comparison of the efficacy and safety of tofacitinib and baricitinib in patients with active rheumatoid arthritis: aBayesian network meta-analysis of randomized controlled trials.

The relative efficacy and safety of tofacitinib and baricitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) or biologics. We performed aBayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and baricitinib in combination with DMARDs in RA patients with an inadequate DMARD or biologic response. Twelve RCTs including 5883patients met the inclusion criteria. There were 15pairwise comparisons including 10direct comparisons of 6interventions. Tofacitinib 10 mg + methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of being the best treatment to achieve the ACR20 response rate (SUCRA = 0.865), followed by baricitinib 4 mg + MTX (SUCRA = 0.774), baricitinib 2 mg + MTX (SUCRA = 0.552), tofacitinib 5 mg + MTX (SUCRA = 0.512), adalimumab + MTX (SUCRA = 0.297), and placebo + MTX (SUCRA <0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, baricitinib + MTX, adalimumab + MTX, or placebo + MTX. In RA patients with an inadequate response to DMARDs or biologics, tofacitinib 10 mg + MTX and baricitinib 4 mg + MTX were the most efficacious interventions and were not associated with asignificant risk of serious adverse events.

Circulating cell free DNA: a marker to predict the therapeutic response for biological DMARDs in rheumatoid arthritis.

To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA). The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA. The concentration of ccfDNA in RA patients at baseline was higher than healthy controls (P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not (P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA (P = 0.00011). After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.

KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthritis patients

Context: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response.Materials and methods: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05.Results: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043).Discussion and conclusions: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.

Evaluation of the Safety and Effectiveness of Add-On Tacrolimus in Patients with Rheumatoid Arthritis Who Failed to Show an Adequate Response to Biological DMARDs: The Interim Results of a Specific Drug Use-Results Survey of Tacrolimus

BackgroundTacrolimus (TAC) is an immunosuppressive macrolide that blocks T-cell activation by specifically inhibiting calcineurin. TAC was approved in Japan for the treatment of rheumatoid arthritis (RA) in 2005. However, the safety and effectiveness of TAC adding on to biological disease-modifying anti-rheumatic drugs (DMARDs) in the real clinical setting may not be clear enough.ObjectivesWe report here the interim results of post marketing surveillance (PMS) of TAC adding on to biological DMARDs in RA patients who failed to show an adequate response to biological DMARDs.MethodsPatients who had an inadequate response to biological DMARDs were enrolled. An inadequate response to biological DMARDs was defined as that all of the following conditions were met: a Simplified Disease Activity Index (SDAI) score of >3.3 when TAC was started; both the tender joint count and swollen joint count were the same or increased compared with those at 4–8 weeks prior to TAC; and biological DMARDs were used for at least 8 weeks prior to TAC. This study was conducted in compliance with the ministerial ordinance on “Good Post-Marketing Study Practice” (GPSP).ResultsThe safety data collection and evaluation for 172 patients and effectiveness data collection and evaluation for 165 patients were reported. The mean age was 61.9 years. Adverse drug reactions occurred in 18 patients. The mean SDAI decreased from 20.1 at baseline to 11.7 at week 24.ConclusionsTAC is well tolerated and effective when added on to biological DMARDs in RA patients who failed to achieve an adequate response to biological DMARDs.

Association of the ABCB1 C3435T polymorphism with responsiveness to and toxicity of DMARDs in rheumatoid arthritis : A meta-analysis.

The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5studies on the response to DMARDs, and 5on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756-1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516-1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI 0.456-3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259-0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.

Factors associated with the initiation of biologic disease-modifying antirheumatic drugs in Texas Medicaid patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management. Few studies have examined the factors associated with the transition from nonbiologic DMARDs, the first-line therapy for RA, to biologic DMARDs in RA patients. To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with initiation of biologic DMARDs. This was a retrospective study using the Texas Medicaid prescription and medical claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years) with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic DMARD use during the 6-month pre-index period, and a minimum of 2 prescription claims for the same nonbiologic DMARD during the post-index period were included in the study. The index date was defined as the date when the first nonbiologic DMARD claim was made. Predictors of initiation of biologic DMARDs were age, gender, race, adherence (proportion of days covered), persistence to nonbiologic DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use, glucocorticoid use, and rheumatologist visit. Logistic regression was used to examine the factors associated with the initiation of biologic DMARDs. A total of 2,714 patients were included. After controlling for patient characteristics, logistic regression showed, that compared with methotrexate (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P less than 0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P less than 0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less likely to initiate biologic DMARDs compared with nonbiologic DMARD monotherapy users (OR = 0.609, 95% CI = 0.463-0.803, P = 0.0004). With each year increase in age, patients were 1.6% less likely to start biologic DMARDs (OR = 0.984, 95% CI = 0.975-0.993, P = 0.0006). Compared with glucocorticoid users, glucocorticoid nonusers were 53.8% less likely to start on biologic DMARDs (OR = 0.462, 95% CI = 0.372-0.573, P less than 0.0001). Patients with CCI scores of ≥ 3 were approximately 1.6 times more likely to initiate biologic DMARDs than those with CCI scores of 1 (OR = 1.618, 95% CI = 1.228-2.132, P = 0.0006). Younger age, CCI scores ≥3, glucocorticoid use, MTX users (vs. SSZ and HCQ users), and nonbiologic DMARD monotherapy users (vs. dual therapy users) were significantly associated with higher likelihood to initiate biologic DMARDs. Recognizing these potential factors that drive the initiation of biologic DMARDs in this patient population, health care providers and Texas Medicaid should take measures to achieve optimal therapy for RA patients through thorough RA medication evaluation, well-structured RA monitoring programs, and patient education.

PMS9 - Factors Associated With The Initiation Of Biologic Disease Modifying Antirheumatic Drugs In Texas Medicaid Patients With Rheumatoid Arthritis

BACKGROUND: Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management. Few studies have examined the factors associated with the transition from nonbiologic DMARDs, the first-line therapy for RA, to biologic DMARDs in RA patients. OBJECTIVE: To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with initiation of biologic DMARDs. METHODS: This was a retrospective study using the Texas Medicaid prescription and medical claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years) with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic DMARD use during the 6-month pre-index period, and a minimum of 2 prescription claims for the same nonbiologic DMARD during the post-index period were included in the study. The index date was defined as the date when the first nonbiologic DMARD claim was made. Predictors of initiation of biologic DMARDs were age, gender, race, adherence (proportion of days covered), persistence to nonbiologic DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use, glucocorticoid use, and rheumatologist visit. Logistic regression was used to examine the factors associated with the initiation of biologic DMARDs. RESULTS: A total of 2,714 patients were included. After controlling for patient characteristics, logistic regression showed, that compared with methotrexate (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P < 0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P < 0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less likely to initiate biologic DMARDs compared with nonbiologic DMARD monotherapy users (OR = 0.609, 95% CI = 0.463-0.803, P = 0.0004). With each year increase in age, patients were 1.6% less likely to start biologic DMARDs (OR = 0.984, 95% CI = 0.975-0.993, P = 0.0006). Compared with glucocorticoid users, glucocorticoid nonusers were 53.8% less likely to start on biologic DMARDs (OR = 0.462, 95% CI = 0.372-0.573, P < 0.0001). Patients with CCI scores of ≥ 3 were approximately 1.6 times more likely to initiate biologic DMARDs than those with CCI scores of 1 (OR = 1.618, 95% CI = 1.228-2.132, P = 0.0006). CONCLUSIONS: Younger age, CCI scores ≥3, glucocorticoid use, MTX users (vs. SSZ and HCQ users), and nonbiologic DMARD monotherapy users (vs. R ESEAR C H

SAT0096 Mean Platelet Volume as a Biomarker Representing Seropositivity and Treatment Responses in Rheumatoid Arthritis

BackgroundChronic inflammation is known to be associated with increased cardiovascular (CV) event rate in rheumatoid arthritis (RA). Platelet activation may be a link in the pathophysiology of diseases leading to...

Risk of hepatotoxicity with add-on leflunomide in rheumatoid arthritis patients

Combination of disease-modifying antirheumatic drugs (DMARDs) is increasingly used in the treatment of rheumatoid arthritis (RA) patients. Hepatotoxicity has been an important safety concern with DMARDs therapy. Though leflunomide (CAS 75706-12-6) has emerged as an effective oral DMARD, its use is associated with hepatotoxicity. Limited data is available regarding hepatotoxic risk when leflunomide is used in combination therapy in RA patients. An open-label, prospective study was conducted to evaluate the hepatotoxic risk after addition of leflunomide with other DMARDs in RA patients, who did not respond to their ongoing DMARD therapy. A total of 46 patients were enrolled and leflunomide was given as add-on therapy with earlier DMARDs. Biochemical parameters of serum aminotransferase levels (AST and ALT) were estimated at the baseline and then every month after addition of leflunomide. Study results showed that 13.0% patients developed > 1.5 to < 2 times upper limit of normal (ULN) elevation; 6.5% patients developed > 2 to < 3 times the ULN elevation and 2.2% patients developed > 3 times the ULN elevation. In 20% of the patients with hepatic enzyme elevations, enzyme levels returned to normal within 4-6 weeks after discontinuation of leflunomide therapy, whereas in 50% of patients the dose of leflunomide was reduced from 20 mg/day to 10 mg/day for normalization of enzymes levels. 30% of patients were continued with leflunomide without dose reduction. None of the patients showed clinical signs and symptoms of hepatotoxicity. Leflunomide therapy with other DMARDs requires strict monitoring of serum aminotransferases.

Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

IntroductionThe metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.MethodsMetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS.ResultsMetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33–0.81, P = 0.004).ConclusionsThe prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years.