Initiation Of DMARDs Research Articles

A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.

Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as<or≥3months); and dosage (low as<2.5, medium as 2.5 to <7.5 and high as≥7.5mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio=0.89, 95% confidence interval=0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P<0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. AbbVie Inc.

The impact of rheumatologist-performed ultrasound on diagnosis and management of inflammatory arthritis in routine clinical practice

BackgroundRheumatologists increasingly perform ultrasound (US) imaging to aid diagnosis and management decisions. There is a need to determine the role of US in facilitating early diagnosis of inflammatory arthritis. This study describes the impact of US use by rheumatologists on diagnosis and management of inflammatory arthritis in routine UK clinical practice.MethodsWe conducted a prospective study in four secondary care rheumatology clinics, each with one consultant who routinely used US and one who did not. Consenting patients aged > 18, newly referred with suspected inflammatory arthritis were included. Data were collected both retrospectively from medical records and via a prospectively-completed physician questionnaire on US use. Analyses were stratified by US/non-US groups and by sub-population of rheumatoid arthritis (RA)-diagnosed patients.Results258 patients were included; 134 US and 124 non-US. 42% (56/134) of US and 47% (58/124) of non-US were diagnosed with RA. Results described for US and non-US cohorts, respectively as follows. The proportion of patients diagnosed at their first clinic visit was 37% vs 19% overall (p = 0.004) and 41% vs 19% in RA-diagnosed patients (p = 0.01). The median time to diagnosis (months) was 0.85 vs 2.00 (overall, p = 0.0046) and 0.23 vs 1.38 (RA-diagnosed, p = 0.0016). Median time (months) to initiation on a DMARD (where initiated) was 0.62 vs 1.41 (overall, p = 0.0048) and 0.46 vs 1.81 (RA-diagnosed, p = 0.0007).ConclusionIn patients with suspected inflammatory arthritis, routine US use in newly referred patients seems to be associated with significantly earlier diagnosis and DMARD initiation.

The role of ultrasound in diagnosing rheumatoid arthritis, what do we know? An updated review.

To clarify if musculoskeletal ultrasound (MSUS) improves early diagnosis of RA when added to the clinical examination of patients with possible arthritis. We performed a systematic literature review of original studies dealing with the value of MSUS in the early diagnosis of RA. Studies were identified using the databases of PubMed, EMBASE and Cochrane library. Only studies in English investigating populations with non-classified arthritis or arthralgia were included. Fifteen original studies investigating the added value of MSUS in diagnosing RA were identified. They differed in sample size, study population, serology status, number of joints investigated and regarding the ultrasound machines and probes used. Thirteen out of 15 studies concluded that use of MSUS had an added value compared to clinical examination and laboratory evaluation alone for diagnosing RA. One study found that MSUS did not add substantial discriminatory value for predicting RA in an early arthritis cohort when added to routine assessment. However, in this study only 16 joints were examined (wrists and MTP 3-5 were not included). One study investigated only seropositive patients and found no significant advantage of MSUS on patient level although a trend was noted. Accordingly, two other studies found MSUS to be useful especially in seronegative patients. The use of MSUS adds value in diagnosing early RA, especially in seronegative arthritis. However, no study to date has documented any effect of DMARD initiation based on MSUS findings (subclinical arthritis) alone. More studies investigating this matter are warranted.

Achievement of NICE quality standards for patients with new presentation of inflammatory arthritis: observations from the National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis.

A national audit was performed assessing the early management of suspected inflammatory arthritis by English and Welsh rheumatology units. The aim of this audit was to measure the performance of rheumatology services against National Institute for Health and Care Excellence (NICE) quality standards (QSs) for the management of early inflammatory arthritis benchmarked to regional and national comparators for the first time in the UK. All individuals >16 years of age presenting to rheumatology services in England and Wales with suspected new-onset inflammatory arthritis were included in the audit. Information was collected against six NICE QSs that pertain to early inflammatory arthritis management. We present national data for the 6354 patients recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health boards in England and Wales participated in this audit. Only 17% of patients were referred by their general practitioner within 3 days of first presentation. Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of patients. The target of DMARD initiation within 6 weeks of referral was achieved in 53% of RA patients; 36% were treated with combination DMARDs and 82% with steroids within the first 3 months of specialist care. Fifty-nine per cent of patients received structured education on their arthritis within 1 month of diagnosis. In total, 91% of patients had a treatment target set; the agreed target was achieved within 3 months of specialist review in only 27% of patients. Access to urgent advice via a telephone helpline was reported to be available in 96% of trusts. The audit has highlighted gaps between NICE standards and delivery of care, as well as substantial geographic variability.

Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data.

Objective. To determine whether time to treatment following symptom onset differs between RA patients according to autoantibody status.Methods. A single-centre retrospective analysis of a UK early RA inception cohort was first undertaken to identify those components of the patient journey that differed by serological subtype. Data from a UK national audit of early inflammatory arthritis patients was accessed to replicate the key finding.Results. A total of 173 RA patients were diagnosed over a 31-month period, of whom 80 (46%) were ACPA/RF double-seropositive (ACPA+/RF+), 53 (31%) ACPA−/RF−, 17 (10%) ACPA+/RF− and 23 (13%) RF+/ACPA−. Overall, ACPA+/RF+ patients experienced significantly longer symptom duration before DMARD initiation. This was accounted for by delays in their presentation to primary care following symptom onset—a finding that was robustly confirmed in an independent dataset of 2192 UK early RA patients. In contrast, ACPA−/RF− patients were significantly more likely to experience delays in DMARD initiation after presenting to secondary care.Conclusion. Causes of treatment delays in early RA differ according to patients’ autoantibody status. More insidious symptom onset and/or distinct health-seeking behaviours among ACPA+/RF+ patients may contribute to late presentations in primary care, whereas ACPA−/RF− patients experience delayed diagnosis and treatment in secondary care. These observations inform the research agenda, potentially influencing the design of service delivery for early arthritis patients.

Real-world evaluation of TNF-inhibitor utilization in rheumatoid arthritis

Objectives:To evaluate 12-month treatment patterns, healthcare resource use (HCRU), and costs for patients with rheumatoid arthritis (RA), following initiation of index TNF inhibitors (TNFi) and subsequent biologic DMARDs (bDMARDs).Methods:This was a retrospective cohort analysis of adults with RA newly initiating TNFi in the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Databases during 2010–2013. A sub-group of patients who switched to a bDMARD within 12 months post-index and within 180 days of last index TNFi were subsequently evaluated over 12 months. TNFi/bDMARD treatment patterns were characterized as: continuers, no gap >180 days in prescription/administration of index TNFi; discontinuers, gap >180 days; switchers, initiated new bDMARD. Concomitant conventional synthetic DMARD use, co-morbid chronic illnesses, and RA severity were assessed. All-cause/RA-related HCRU and costs were evaluated 12 months post-index.Results:Of 9567 identified patients, 67.2%, 17.3%, and 15.4% were continuers, discontinuers, and switchers, respectively. Switchers had the highest 12-month unadjusted mean all-cause costs of $34,585 vs $33,051 for continuers (p = 0.1158) and $24,915 for discontinuers (p < 0.0001; discontinuers vs continuers, p < 0.0001). RA-related costs comprised 82.8%, 31.4%, and 85.7% of total costs for continuers, discontinuers, and switchers, respectively. Of 764 switchers, 68.2% switched to alternative TNFi (cyclers), the rest to non-TNFi bDMARDs; 36.7% of patients who switched to TNFi switched again (to third-line bDMARD) vs 27.6% (p = 0.0313) of those who switched to non-TNFi bDMARDs. Switchers to non-TNFi bDMARDs had higher mean 12-month all-cause costs of $76,580 compared with $50,689 for switchers to alternative TNFi (p < 0.0001); biologic-administration visits comprised 78.8% of the greater total RA-related costs of switchers to non-TNFi bDMARDs.Conclusions:Real-world TNFi discontinuation/switching rates correspond to randomized controlled trial non-response rates. TNFi cycling is common and associated with an increased likelihood of switching to third-line bDMARD. Switching to non-TNFi bDMARDs was associated with higher costs, mostly attributed to in-office administrations.

The impact of multimorbidity status on treatment response in rheumatoid arthritis patients initiating disease-modifying anti-rheumatic drugs.

When treating RA patients, remission (REM) or at least low disease activity (LDA) is the ultimate therapeutic goal. The aim of this study was to assess the impact of multimorbidity on achieving REM or LDA. In a prospective RA cohort, we identified patients initiating any DMARD with follow-up data 1 year after. Treatment effects were measured using the clinical disease activity index (CDAI) and the modified health assessment questionnaire (MHAQ); multimorbidity status was assessed using a counted multimorbidity index (cMMI). The proportion of patients reaching REM or LDA 1 year after DMARD commencement with respect to the cMMI was evaluated. In regression models, we calculated the odds ratio of achieving REM or LDA, and predicted CDAI and MHAQ 1 year after DMARD commencement for various levels of cMMI, adjusting for age, sex, disease duration, serostatus, disease activity at DMARD commencement, number of previous DMARDs, and type of DMARD, steroid and NSAID use. A total of 815 patients started DMARDs; 414 were on the same DMARD after 1 year. The proportion of these patients achieving REM or LDA after 1 year was significantly lower in the patients with higher cMMI, following a linear trend (P < 0.01). After accounting for covariates, the odds ratio for REM associated with each additional morbidity in the cMMI was 0.72 (95% CI 0.55, 0.97) and 0.81 (95% CI 0.70, 0.94) for LDA. One year after DMARD initiation, CDAI (+0.16 per additional morbidity) and MHAQ scores (+0.15 per additional morbidity) were significantly worse (both P < 0.05). Increased multimorbidity negatively affects the therapeutic goal of REM and LDA.

Safety of biologic and nonbiologic disease-modifying antirheumatic drug therapy in veterans with rheumatoid arthritis and hepatitis B virus infection: a retrospective cohort study.

IntroductionWe evaluated the safety of current treatment regimens for patients with RA and HBV in a large US cohort.MethodsWe identified biologic and nonbiologic treatment episodes of RA patients using 1997 to 2011 national data from the US Veterans Health Administration. Eligible episodes had evidence of HBV infection (HBV surface antigen, HBV core antibody, HBV e-antibody and/or HBV DNA) and had a baseline alanine aminotransferase (ALT) <1.5 times the upper limit of laboratory normal within 90 days prior to initiation of a new biologic or nonbiologic DMARD. The main outcome of interest was hepatotoxicity, defined as ALT elevation >100 IU/mL. Results were reported as the cumulative incidence of treatment episodes achieving hepatotoxicity at 3, 6 and 12 months post biologic exposure.ResultsFive hundred sixty-six unique RA patients with HBV contributed 959 treatment episodes. Mean age was 62.1 ± 10.3 years; 91.8% were male. Hepatotoxicity was uncommon, with 26 events identified among 959 episodes (2.7%) within 12 months. Hepatotoxicity was comparable between biologic and nonbiologic DMARDs (2.6% vs. 2.8%, P = 0.87). The median time between HBV screening and starting a new RA drug was 504 days (IQR 144, 1,163). Follow-up HBV testing occurred among 14 hepatotoxicity episodes (53.8%) at a median of 202 days (IQR 82, 716) from the date of ALT elevation. A total of 146 (15.2%) treatment episodes received at least one test for HBV DNA at any point in the observation period.ConclusionsAmong US veterans with RA and HBV the risk of hepatotoxicity is low (2.7%), and comparable between biologic and nonbiologic DMARDS (2.8% vs. 2.6%, P = 0.87). HBV testing associated with DMARD initiation or hepatotoxicity was infrequent.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0628-z) contains supplementary material, which is available to authorized users.

THU0264 In Early Rheumatoid Arthritis (Espoir Cohort), Serum CCL19 Level is Associated with Disease Activity, Autoantibody Secretion and 3-Year Radiographic Progression: Data from the Espoir Cohort

BackgroundThe interferon (IFN) signature has mainly been studied in established rheumatoid arthritis (RA), and was associated with poor response to rituximab. Serum levels of CCL2 (Monocyte Chemotactic Protein 1, MCP-1),...

A170: Neoplasms in Pediatric Patients with Rheumatic Diseases Exposed to Biologics—A Quarternary Centre's Experience

Background/Purpose:Biologic therapies have revolutionized the management of rheumatic diseases of childhood. However, these medications are associated with adverse effects including the possible development of neoplasms. The aim of our study was to determine the rate as well as risk factors for the development of neoplasms in patients with JIA treated with biologics.Methods:We performed a retrospective review of the rheumatology biologic registry (RBR) at The Hospital for Sick Children (SickKids), Toronto, Canada, one of the largest quarternary pediatric referral centres in North America. Demographic and neoplastic data, clinical course and medication history were extracted from the RBR and clinical charts. Unless specified, data was expressed as median (IQR). The study was approved by the SickKids Ethics Review Board.Results:The cohort consisted of 357 patients with rheumatic diseases who were on one or more biologics between January 1997 and August 2013. Juvenile Idiopathic Arthritis (JIA) was the most common diagnosis [302/357 (84.5%)]. A total of 6/357 (1.68%) patients developed a neoplasm: 4 with JIA, 1 each with idiopathic uveitis and polyarteritis nodosa. (Refer to t87) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Neoplasm Nasopharyngeal carcinoma 1. Tonsillar lymphoproliferative disorder (LD) in 2006 Clear cell renal carcinoma Hepatosplenic lymphoma Small blue cell sarcoma, undifferentiated Pilomatricoma 2. Renal carcinoma in 2011 Rheumatic Disease (RD) Idiopathic Uveitis Polyarteritis Nodosa Poly JIA (RF negative) Systemic JIA Oligo JIA (extended) Oligo JIA (extended) Age of onset of RD (years) 10.8 1.1 8.2 4.7 1.6 2.0 Sex Male Male Female Female Female Female DMARD(s), Cytotoxic agents MTX (4.7) MTX (1.2); MTX (6.2); MTX (3.6); MTX (7.2); CSA (3.2); (Time (years)) AZA (NA); LFN(0.2); CSA (0.9); LFN (0.2) AZA (4.3); Abbreviations: ‐Methotrexate (MTX), CYC (1.5) CSA (1.5); Tacrolimus (5.0); MTX (6.0); ‐Azathioprine (AZA), AZA (1.2); Etoposide (6 cycles over 34 days); LFN (2.8) ‐Leflunomide (LFN), SSA (0.9) Thalidomide (0.6) Cyclophosphamide (CYC), ‐Cyclosporine (CSA), ‐Sulfasalazine (SSA) ‐Not available (NA) Biologic(s) Infliximab (3.3) Infliximab (7.5) Etanercept (4.8) Etanercept (0.1); Etanercept (5.2) Infliximab (8.2); (Time (years)) Infliximab (1.7); Etanercept (1.5) Anakinra (1.9) Time to neoplasm (years) 5.3 1. 14.1 15.8 11.8 16.7 12.7 2. 18.6 Time from DMARD to neoplasm (years) 4.7 1. 6.8 17.6 11.8 8.4 12.6 2. 11.4 Time from Biologic to neoplasm (years) 3.3 1. 4.8 10.6 8.6 5.3 1.3 2. 9.3 Family history of neoplasm Maternal grandfather: lung cancer; Maternal grandmother: cervical cancer Mother died due to breast cancer. NA NA NA Strong family history of colon cancerAmongst patients with neoplasms, the median (IQR) age at rheumatic disease onset was 3.4 (1.7–7.3) years and the age of diagnosis of the neoplasm was 16.3 (15.3–17.9) years. All cancers were malignant except in patient 6 which was of a benign nature. On average, patients had exposure to 3 DMARDs (range 1–5), with methotrexate as the commonest DMARD used in 5/6 patients prior to diagnosis of the neoplasm. The time from the disease onset to initiation of DMARD was 3.9 (0.4–7.9) years. The time from the DMARD initiation and the diagnosis of a neoplasm was 10.1 (7.2–12.3) years. For methotrexate alone, the duration of use was 5.4 (3.9–6.1) years. All patients diagnosed with a neoplasm, had received both, DMARD(s) and biologic(s). 2 patients were on infliximab alone, 2 on etanercept alone and 2 on multiple biologics of which etanercept and infliximab were both used. The time between onset of a biologic and diagnosis of a neoplasm was 5.0 (3.6–7.7) years. Two patients (2 and 4) also received medications which are associated with the development of the neoplasms (cyclophosphamide or etoposide).Conclusion:Majority of neoplasms were of uncommon morphology and site as well as aggressive in nature. The neoplasms developed late after drug exposure with a median duration to diagnosis of neoplasm of 10.1 years on a DMARD and 5.5 years on a biologics. Whilst DMARDs and biologics are effective for the management of rheumatic diseases, patients with refractory disease requiring ongoing drug therapies should have malignancy/ neoplasm surveillance included as part of routine clinical care. Comparison of patients on biologics with and without neoplasms is in progress.

A36: Long‐term Pharmacokinetics of Body Surface Area‐Adjusted Doses of Golimumab Following Repeated Subcutaneous Administrations in Pediatric Patients With Polyarticular Juvenile Idiopathic Arthritis

Background/Purpose:To assess the pharmacokinetics (PK) and PK‐efficacy correlations of body surface area (BSA)‐adjusted dosing of 30 mg/m2 golimumab administered subcutaneously (SC) every 4 weeks (q4w) + methotrexate (MTX) through Week 48 in pediatric patients (ages 2 to &lt;18 years) with juvenile idiopathic arthritis (JIA).Methods:GO‐KIDS is a randomized‐withdrawal, double‐blind, placebo‐controlled, parallel‐group, multicenter Phase 3 trial of SC golimumab 30 mg/m2 (maximum 50 mg) q4w + MTX (10/N30 mg/m2/week) in pediatric patients with active JIA despite current MTX therapy (median 15 mg/week). PK, safety, and efficacy evaluations were performed q4w through week 16. At Week 16, patients who were ACR JIA 30 responders were randomized (1:1) to 30 mg/m2 golimumab or placebo q4wks through Week 48 with GLM reinstituted upon flare (defined as per JIA ACR flare criteria) or initiation of new DMARDS, biologics, systemic immunosuppressives. Serum trough concentrations were also obtained at Weeks 12, 16, 24 and 48. Serum golimumab trough concentrations for 154 patients were determined via a validated immunoassay. The relationships of ACR pediatric 30 response and disease flare status with steady‐state trough levels at Week 48 were assessed.Results:Trough serum golimumab concentrations in patients receiving SC 30 mg/m2 golimumab q4w through Week 48 were maintained over time. Steady‐state trough golimumab levels were similar across different age groups, and were also similar to those seen in adult RA patients who received 50 mg SC q4w in Phase III clinical trials. There were no apparent differences in pediatric ACR JIA 30 response rates and disease flare rates among the 4 groups of JIA patients categorized by the 4 quartiles of steady‐state trough golimumab levels at Week 48. In addition, there were no apparent PK differences between patients who did and did not experience disease flares in the randomized golimumab group. Mean (SD) and median trough serum golimumab concentrations (mg/mL) by age groups and body weight quartiles are presented in the . Age Groups (Years) 2–6 ≥6 to 12 ≥12 Combined Week 12 Mean (SD) 1.42 (0.744) 0.95 (0.593) 1.21 (0.711) 1.14 (0.685) Median 1.77 0.92 1.29 1.46 Week 16 Mean (SD) 1.17 (0.650) 0.96 (0.721) 1.24 (0.836) 1.13 (0.780) Age Groups (Years) 2–6 ≥6 to 12 ≥12 Combined Median 1.22 0.89 1.23 1.10 Week 24 Mean (SD) 1.30 (0.833) 1.08 (0.876) 1.23 (1.003) 1.19 (0.927) Median 1.57 1.12 1.08 1.12 Week 48 Mean (SD) 0.86 (0.574) 0.95 (0.715) 1.19 (0.777) 1.08 (0.736) Median 0.87 0.73 1.25 0.95 Body Weight Quartiles (kg) ≤15.60 &gt;15.60 to ≤18.60 &gt;18.60 to ≤21.90 &gt;21.90 Week 12 Mean (SD) 1.09 (0.723) 1.09 (0.622) 1.54 (0.649) 0.90 (0.642) Median 1.13 1.09 1.49 0.83 Week 16 Mean (SD) 0.99 (0.622) 1.07 (0.739) 1.60 (0.845) 0.99 (0.806) Median 0.90 1.12 1.76 0.89 Week 24 Mean (SD) 0.91 (0.799) 1.38 (0.780) 1.52 (1.243) 1.05 (0.844) Median 0.61 1.37 1.42 1.00 Week 48 Mean (SD) 0.74 (0.468) 1.22 (0.852) 1.59 (0.498) 0.94 (0.789) Median 0.75 1.10 1.55 0.81Conclusion:Treatment with 30 mg/m2 SC golimumab q4w + MTX resulted in sustained steady‐state trough serum golimumab concentrations over time. The PK/efficacy correlation analyses demonstrated that the BSA‐adjusted dosing regimen of 30 mg/m2 SC golimumab q4w provided adequate drug exposure for the desired efficacy.

AB1361 Diagnostic and therapeutic delay of rheumathoid artritis patients in catalonia (spain) and their relationship with specialized healthcare units. The audit study

BackgroundThe diagnosis and therapeutic approach to early onset rheumatoid arthritis (RA) patients may be influenced by their access to specialized healthcare units.ObjectivesTo assess diagnostic and therapeutic delays in RA in...

FRI0356 Clinical remission in 291 juvenile idiopathic arthritis patients treated with biological agents

Objectivesdetermine response to biological therapy (BT) in Juvenile Idiopathic Arthritis (JIA) pts in term of clinical remission on medication (CRM) according to Wallace criteria, and to identify baseline factors predictors...

PMS47 The Health and Economic Consequences of Delay in Starting Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis

THE HEALTH AND ECONOMIC CONSEQUENCES OF DELAY IN STARTING DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) IN RHEUMATOID ARTHRITIS Van doornum S1, Roberts L2, Reed MD3, Liew D1 1The University of Melbourne, Parkville, Vic, Australia, 2James Cook University, Douglas, Queensland, Australia, 3Sir Charles Gairdiner Hospital, Nedlands, Western Australi, Australia OBJECTIVES: Several international studies suggest that the time between symptom onset and DMARD initiation in RA patients is longer than is considered optimal. We sought to assess the health economic impact of this delay in an Australian context. METHODS: The delay in DMARD initiation was estimated from a 2005 study of 96 Australian RA patients referred to one public and four private rheumatology practices. RA-associated utilities and costs were sourced from published data. Patients not taking and taking DMARD therapy were assumed to have utilities of 0.443 and 0.543, respectively. The annual direct costs of RA, excluding DMARDs, was AUD $3780, and of DMARD therapy was $2658. It was conservatively assumed that DMARD therapy did not reduce non-DMARD RA costs. RESULTS: In the 2005 study, the mean time from symptom onset to initiation of DMARD therapy was 1.48 years. Over this time a mean of 0.65 QALYs would have been lived per patient and $5579 of direct health care costs incurred. Had DMARDs been commenced at symptom onset, 0.80 QALYs would have been lived per patient, and $9503 of direct health care costs incurred. Hence early initiation of DMARDs would have saved 0.15 QALYs at a cost of $3924 per person, equating to an incremental cost-effectiveness ratio (ICER) of $26,583 per QALY saved. An additional $3400 could be spent per patient to reduce the time to DMARD initiation before the ICER breached the arbitrary cut-off of $50,000 per QALY saved. Our analysis was conservative in it did not consider the long-term health and cost savings associated with avoidance of permanent joint damage. CONCLUSIONS: The considerable delay in the initiation of DMARD therapy among patients with RA leads to significant health loss. Reducing the time to initiation of DMARDs represents a cost-effective means of reducing the burden of RA.

Prospective evaluation of clinical profile and treatment outcome of patients presenting with polyarthritis diagnosed as rheumatoid arthritis

Introduction: Polyarthritis is a common presentation of patients attending medicine outpatient department. Among various causes Rheumatoid arthritis is the commonest and a well established case has distinct characteristic features. However the early presentation of this disease has not been clear thus leading to delay in treatment. The objectives of this study was to identify the various causes of polyarthritis in our clinical practice, discuss the varied clinical presentation of rheumatoid arthritis including early Rheumatoid arthritis and to evaluate the treatment response during one year follow up. Methods: Prospective longitudinal study conducted in a teaching hospital over a two years period Results: Rheumatoid arthritis was the commonest cause of polyarthritis (77.8%) with a period prevalence of 0.7%. Early presentation included atypical features like asymmetry, unilateral presentation, manifesting within 2 months to 2 years of diagnosis. 43% (n=18) of the patients had swelling and tenderness in overused joints 1.5 years prior to full clinical manifestation. Flitting or migratory joint pain not considered to be a feature of rheumatoid arthritis was also present in 14.3% (n=6) patients with mean duration of 1.5 years prior to full blown presentation. MCPJ (metacarpophalyngeal joints) and PIP (proximal interphalyngeal joints) were involved in 90%. Treatment response with Methotrexate as a single DMARD was good as compared with DAS 28 ESR score. Conclusions: RA is a common arthritis with varied clinical presentation. Recognition of early symptoms is needed for early diagnosis and initiation of DMARD. Methotrexate as a DMARD is effective and should be initiated early. DOI: http://dx.doi.org/10.3126/mjsbh.v10i2.6459 Medical Journal of Shree Birendra Hospital July-Dec 2011 10(2) 22-28

Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis

Glucocorticoids are widely used anti-inflammatory and immunosuppressive drugs for rheumatoid arthritis (RA). The disease-modifying potential of low to medium doses of glucocorticoids has been reconfirmed in the past decade, and co-administration of DMARDs and glucocorticoids has become standard in many treatment protocols, especially those for early disease stages but also for long-standing RA. The glucocorticoid regimens used range from continuous low doses to intermittent high doses. Studies of the rationale for and clinical use of glucocorticoids as co-therapy with DMARDs in RA have shown that this approach has a place in modern (tight control) treatment strategies, and that glucocorticoid co-therapy has disease-modifying effects during the first 2 years of treatment in patients with early RA. Furthermore, medium and high doses of glucocorticoids are useful for bridging the interval between initiation of DMARDs and onset of their therapeutic effect. Intra-articular glucocorticoids give good local control and have been used in tight control strategies. New glucocorticoid compounds are becoming available for clinical use that might have an enhanced risk:benefit ratio. Better monitoring of glucocorticoid use will also improve this ratio, and help to allay both patient and rheumatologist concerns about treatment-related adverse effects.

Lag time between onset of symptoms and diagnosis in Venezuelan patients with rheumatoid arthritis

A retrospective study in a hospital-based sample of Venezuelan patients with rheumatoid arthritis was made to estimate the lag time between onset of symptoms, diagnosis, and initiation of DMARD treatment. Medical records and in-person interview of patients to fill in a questionnaire collecting information on demographics and initiation of symptoms, first consultation with any physician, time of diagnosis, and initiation of first disease-modifying anti-rheumatic drug were reviewed. We performed descriptive statistics and multivariable linear regression analysis. Mean lag time between symptom onset and diagnosis of rheumatoid arthritis was 40.5 months (range 1-424). Mean lag time between onset of symptoms and first consultation with a physician and between first consultation and diagnosis was 16.3 and 23.9 months, respectively. Mean lag time between onset of symptoms and initiation of DMARD treatment was 56.9 months. A definitive diagnosis of rheumatoid arthritis was done by a rheumatologist in 251 patients (92.3%). First consultation with an orthopedist or a primary care physician, first consultation in a public versus a private health center, and diagnosis before 2000 were associated with longer lag time between onset of symptoms and diagnosis. Venezuelan patients with rheumatoid arthritis had a marked delay from disease onset to diagnosis and initiation of first DMARD. First consultation with an orthopedist and consultation in a public versus a private health center were the variables with the strongest effect on lag time to diagnosis and to initiation of first DMARD.

Initiation of rheumatoid arthritis treatments and the risk of serious infections

In clinical trials of RA patients on traditional DMARDs, the addition of TNF-alpha antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results. We estimated hospitalization rates for infections following initiation of TNF-alpha antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995-2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002-05 and first episodes of use and explored effects of unmeasured confounders. We identified 28 906 new episodes of medication use, including TNF-alpha antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-alpha antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results. Compared with initiation of MTX alone, initiation of TNF-alpha antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dose-dependent increase in the risk of these infections.

Sedimentary xenoliths and dolerite patch pegmatites from an analcite basalt intrusion

<h3>Background:</h3> The COVID-19 pandemic has caught us all by surprise – from governments to individuals; the medical fraternity being no exception. It has affected all walks of life; with its immense contagiosity, diverse and intriguing pathogenesis and manifestations differing from other viruses. It has indeed left humanity in dark, unchartered waters; particularly in the early months of the pandemic. <h3>Objectives:</h3> This article shares the experience, in a Rheumatology department in a District General Hospital (DGH) in the United Kingdom, of managing patients on Biologic (b) and Targeted Synthetic (ts) DMARDs, in the midst of the COVID-19 Pandemic. <h3>Methods:</h3> All Rheumatology patients at the Princess Alexandra Hospital (PAH) in Harlow newly started on a biologic or targeted synthetic DMARD between 3rd July and 3rd Oct 2020 were identified. These patients had active inflammatory arthritis. Each patient was discussed in a dedicated Multi-Disciplinary Team (MDT) meeting and a consensus on treatment reached in-line with local and National guidelines. <h3>Results:</h3> Of the 50 patients identified; 39 had Rheumatoid Arthritis, 6 had Ankylosing Spondylitis and 5 had Psoriatic Arthritis. Of these 50 patients, 5 patients decided against treatment during the stage of ‘Enhanced Verbal Consent’. These patients were flaring recurrently and were in regular contact with the department. However, they were afraid to start new Biologic treatment because of the risks of Covid-19. The breakdown of the biologic agents used in the remaining 45 patients were as follows: Adalimumab:11, Rituximab: 10, Etanercept: 9, Tofacitinib: 11, Tocilizumab SC: 3, Tocilizumab IV: 1, Sarilumab: 2, Secukinumab: 1, Infliximab: 1, Baricitinib: 1, Apremilast: 1 <h3>Conclusion:</h3> The over-riding principle that guided the Department during the COVID crisis was: <i>primum non nocere</i> (first, do no harm). The adherence to the Case Based Discussions (CBDs) positively impacted on decision making, ensuring safe initiation of Biologic DMARDs even during the height of the pandemic. This is vital to achieve early disease remission. The MDT meetings comprising Doctors, Specialist Pharmacist and Nurse Specialists ensured prompt risk stratification of individual patients. It gave patients the opportunity to be part of the decision-making - evident in the five of the fifty patients, who opted to defer the start date of their treatments. The choice of the new Biologic agent was based on the latest National COVID-19 guidelines. The agents with the shortest half-life were selected. Moreover, patients for Rituximab were given one pulsed infusion, as opposed to two infusions. Only one of the 45 patients started on a Biologic agent over this period, either was tested positive or had symptoms suggestive of COVID-19. <h3>

International Journal of Health Education

<h3>Introduction</h3> The introduction of biological disease-modifying antirheumatic drugs (bDMARDs) has improved the treatment of inflammatory rheumatic diseases dramatically. However, bDMARD treatment failure occurs in 30%–40% of patients due to lack of effect or adverse events, and the tools to predict treatment outcomes in individual patients are currently limited. The objective of the present study is to identify diagnostic, prognostic and predictive biomarkers, which can be used to (1) diagnose inflammatory rheumatic diseases early in the disease course with high sensitivity and specificity, (2) improve prognostication or (3) predict and monitor treatment effectiveness and tolerability for the individual patient. <h3>Methods and analysis</h3> The present study is an observational and translational open cohort study with prospective collection of clinical data and biological materials (primarily blood) in patients with inflammatory rheumatic diseases treated in routine care. Patients contribute with one cross-sectional blood sample and/or are enrolled for longitudinal follow-up on initiation of a new DMARD (blood sampling after 0, 3, 6, 12, 24, 36, 48, 60 months of treatment). Other biological materials will be collected when accessible and relevant. Demographics, disease characteristics, comorbidities and lifestyle factors are registered at inclusion; DMARD treatment and outcomes are collected repeatedly during follow-up. Currently (July 2017), &gt;5000 samples from approximately 3000 patients have been collected. Data will be analysed using appropriate statistical analyses. <h3>Ethics and dissemination</h3> The protocol is approved by the Danish Ethics Committee and the Danish Data Protection Agency. Participants give written and oral informed consent. Biomarkers will be evaluated and published according to the Reporting Recommendations for Tumour Marker (REMARK) prognostic studies, Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines. Results will be published in peer-reviewed scientific journals and presented at international conferences. <h3>Trial registration number</h3> NCT03214263.