Number Of Disease-modifying Antirheumatic Drugs Research Articles

Clinical and immunological responses to COVID-19 vaccination in rheumatoid arthritis patients on disease modifying antirheumatic drugs: a cross-sectional study.

This study was conducted to investigate the immunological and clinical response to COVID-19 vaccination in rheumatoid arthritis (RA) patients receiving disease modifying antirheumatic drugs (DMARDs). A cross-sectional study was conducted among RA patients who received two doses of COVID-19 vaccine within 6 months to one year. Demographic information, comorbidities, vaccination details, and past COVID-19 infection details were collected. Hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were estimated. Disease Activity Score-28 (DAS-28) was calculated for RA patients. Anti-spike antibody (ASA) concentrations were measured, and compared with a healthy control population. Correlations of ASA with age, sex, disease parameters, medication use, and comorbidities were assessed. A total of 103 RA patients and 185 controls were included in the study. RA patients had higher mean age, lower mean Hb, higher ESR, and elevated IL-6 levels. Both groups showed positive results for anti-spike antibodies, with a higher percentage in controls. Among RA patients majority had low DAS-28 score. The number of DMARDs used showed a negative correlation with antibody levels. There was a slight positive correlation between ASA concentration and DAS-28 score. Comorbidities did not significantly influence antibody concentration. No significant differences were found in antibody levels based on the type of COVID-19 vaccine or previous COVID-19 infection or booster dose vaccination among RA patients. The study revealed that RA patients showed a reduced antibody response following COVID-19 vaccination compared to the control group and potentially influenced by immunosuppressive treatments and disease-related factors.

Therapeutic drug monitoring of disease-modifying antirheumatic drugs in circulating leukocytes in immune-mediated inflammatory diseases.

The treatment of immune-mediated inflammatory diseases (IMIDs) is one of the main challenges of modern medicine. Although a number of disease-modifying antirheumatic drugs (DMARDs) are available, there is wide variability in clinical response to treatment among individuals. Therapeutic drug monitoring (TDM) has been proposed to optimize treatment; however, some patients still experience unsatisfactory outcomes, although the blood concentrations of drugs in these patients remain in the therapeutic range. One possible reason for this is that the conventional samples (e.g., whole blood or plasma) used in TDM may not accurately reflect drug concentrations or concentrations of their metabolites at the target site. Hence, more refined TDM approaches to guide clinical decisions related to dose optimization are necessary. Circulating leukocytes or white blood cells have a critical role in driving the inflammatory process. They are recruited to the site of injury, infection and inflammation, and the main target of small molecule DMARDs is within immune cells. Given this, assaying drug concentrations in leukocytes has been proposed to be of possible relevance to the interpretation of outcomes. This review focuses on the clinical implications and challenges of drug monitoring of DMARDs in peripheral blood leukocytes from therapeutic or toxicological perspectives in IMIDs.

Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis

ObjectivesTo evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA).MethodsThis phase 4...

Predictors of health care drop-out in an inception cohort of patients with early onset rheumatoid arthritis

BackgroundRA patients who eventually dropped out of treatment and out of the health care system had potentially disastrous consequences for their health-related quality-of-life outcomes. Objectives of the study were to identify predictors of health care drop out (HDO) in an inception and ongoing cohort of patients with recent onset RA.MethodsCharts from patients attending an early arthritis clinic from February 2004 to December 2015, and standardized follow-up evaluations were reviewed. Patients with HDO (cases) were defined when they did not return back to the clinic for a schedule visit for at least one year. Persistence with therapy was defined as length of time patients complied with RA-treatment. A case-control nested within a cohort design was used to compare baseline and cumulative (up to HDO or equivalent follow-up) variables between cases and paired controls (patients compliant with scheduled visits). Cox regression analysis was used to investigate predictors of HDO. The study was approved by the Institutional Review Board and patients gave written informed consent to have their data published.ResultsData from 170 patients (89.4% female, [mean±SD] age: 38.2±12.6 years) with ≥1 year of follow-up were analyzed; up to December 2015, (median, interquartile rage) follow-up was 86.6 months (43.2–123) during which 35 (20.6%) patients had HDO after 41.1 months (12.1–58.7). Baseline and cumulative variables related to disease activity, treatment and persistence with therapy entered regression models; cumulative number of flares, number of disease-modifying anti-rheumatic drugs /patient and persistence <50% emerged as predictors of HDO. Five cases returned back after (median, range) drop out time of 3.8 years (2.3–5.8); they exhibited higher disability and poorer function than paired controls and outcomes were sustained up to their last follow-up.ConclusionsIn a real clinical setting of an EAC, failure to control disease activity, intensive treatment and poor persistence with therapy predicted HDO. Abandonment of health care had a negative impact on patient outcomes and was sustained even after health care was reinitiated.

Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease.

IntroductionNon-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis.MethodsAdult patients from an ongoing cohort study on treatment adherence were selected if they fulfilled the EULAR/ACR2010 criteria for RA, and were to start with their first DMARDs. Clinical variables were assessed at baseline and every 3 months. Non-adherence was continuously electronically measured and was defined as the proportion of days with a negative difference between expected and observed openings of the medication container out of the 3-month period before DAS28 measurement. Generalized linear mixed models were used to investigate whether the DAS28 related to non-adherence. Covariates included were age, sex, baseline DAS28, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibodies (ACPA) positivity, anxiety, depression, weeks of treatment, number of DMARDs used, education level, use of subcutaneous methotrexate and biological use.ResultsOne hundred and twenty patients met the inclusion criteria for RA. During the study period 17 patients became lost to follow-up. There was a decline in adherence over time for all DMARDs except for prednisone. Non-adherence is a predictor of disease activity in the first 6 months of therapy, adjusted for weeks of treatment, baseline DAS28, and baseline anxiety.ConclusionsNon-adherence relates to disease activity. Therefore, interventions towards enhancing adherence can improve disease outcome.

PMS60 - Biologic Discontinuation In Rheumatoid Arthritis: Experience From Canadian Clinics

The purpose of this study was to describe biologic discontinuation and assess the predictors of discontinuation in Canadian rheumatoid arthritis (RA) patients. In this prospective cohort study, adult patients included in the RHUMADATA database with a diagnosis of RA and treated with at least one biologic since 2003 were selected. The RHUMADATA database includes clinical, laboratory and socioeconomic information of patients with rheumatic diseases followed in three Canadian rheumatology centers (Montreal, Quebec and Rimouski). Patients were followed for three years after therapy initiation or until treatment discontinuation, as measured using pharmacy records. Time to discontinuation and predictors of treatment discontinuation were explored using Cox proportional hazards models. A total of 623 eligible patients were treated with at least one biologic. The average age was 53.2 years (SD=12.4), 77% were women and patients had been diagnosed for an average of 7.7 years. The average time on treatment for the first biologic agent was 1.7 years (SD=2.1). In all, 233 (37%), 326 (52%), 405 (65%), and 438 (70%) patients had stopped their first biologic after 6, 12, 24, and 36 months, respectively. In time-to-event analyses (Cox proportional hazard models), type of work [part time vs. full time; hazard ratio (HR): 1.57; 95% confidence interval (CI): 1.05-2.34] and income [$20,000 to $40,000 vs. less than $20,000 (HR: 1.35; 1.01-1.80) and $80,000 to $100,000 vs. less than $20,000 (HR: 2.16; 1.23-3.80)] were significantly associated with biologic discontinuation over the complete treatment duration. The number of disease-modifying antirheumatic drugs used (HR: 0.89; 0.80-0.99) and use of methotrexate (yes vs. no; HR: 0.80; 0.64-0.99) were associated with a reduced risk of biologic discontinuation. In this real-life Canadian study, high biologic discontinuation rates were observed. This study also suggests that many clinical and socioeconomic variables are predictors of biologic discontinuation in RA patients.

Interstitial lung involvement in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and extraarticular manifestations. Pulmonary involvement is one of the common extraarticular manifestations of RA and may show itself as bronchial tree lesions, rheumatoid nodules, Caplan's syndrome, and lesions in the pleura or pulmonary interstitium (interstitial lung involvement (ILI)). High-resolution computed tomography allows the diagnosis of ILI in RA in nearly 70% of cases although the incidence of ILI may be lower (4 to 30%) depending on diagnostic methods and patient selection criteria. There are several histopathological types of ILI, the differential diagnosis of which can be troublesome. Usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia are major types of RA-associated ILI. UIP-pattern ILI has a more severe course than ILI with other histological patterns. The clinical presentation of ILI may be complicated by the likely toxic effect of a number of disease-modifying antirheumatic drugs (DMARDs) used to treat RA, such as methotrexate and leflunomide, and biological agents (BAs), tumor necrosis factor- α (TNF- α ) inhibitors. The pathogenesis of pulmonary involvement in RA and the role of synthetic DMARDs and BAs in the development of ILI call for further investigations. An extraarticular manifestation, such as ILI, affects the choice of treatment policy in patients with RA. The relevance of a study of ILI is beyond question. The paper discusses the state-of-the-art of investigations in this area.

Immunological effects of adalimumab in rheumatoid arthritis: Results of a Russian national study

A reduction in immunological parameters during therapy for rheumatoid arthritis (RA) can yield new data on the mechanisms of anti-inflammatory action and be of great practical importance since this allows judgment of the depth of impact on the immunological process and therefore may be regarded as one of the components of improvement and remission. Objective: to study the effect of the tumor necrosis factor-a (TNF-а) inhibitor adalimumab (ADA) on a number of key immunological parameters in RA. Subjects and methods. The study included 100 patients (11 men and 89 women) diagnosed with RA from 5 research centers. The patients were observed to have high RA activity: at baseline, DAS28 6.22+0.84 scores; C-reactive protein (CRP) 37.1+34.7 mg/l. The mean number of disease-modifying antirheumatic drugs (DMARDs) used by a patient in the history was 2.1. During 24-week treatment, the patients took ADA in a subcutaneous dose of 40 mg every 2 weeks both alone and in combination with DMARDs. The time course of changes in the serum levels of CRP, IGM rheumatoid factor (RF) and in the concentration of anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies was determined by enzyme immunoassay (EIA) using the Axis-Shield Diagnostics commercial kits (United Kingdom). The levels of TNF-a, interleukin (IL) 6, 12, matrix metalloproteinase 3 (MMP3) were measured in pg/ml by EIA using the Bender MedSystems commercial kits (USA) according to the manufacturer's directions. Results. During ADA therapy, there was a rapid reduction in the level of CRP from 34.3 to 11.317.2 mg/l following 2 weeks (p 0,05). The mean levels of anti-CCP2 antibodies, IL-12, VEGF, and MMP3 remained unchanged. Conclusion. The time course of changes in immunological parameters during ADA treatment demonstrates the rapid and deep effect of TNF-a inhibitors on the different components of the pathogenesis of RA.

Efficacy of Anti-TNF Agents as Adjunctive Therapy for Knee Synovitis Refractory to Disease-Modifying Antirheumatic Drugs in Patients with Peripheral Spondyloarthritis

Our aim was to evaluate the effectiveness of tumour necrosis factor (TNF) inhibitors as add-on therapy for knee synovitis that did not respond to disease-modifying antirheumatic drugs (DMARDs) and other standard treatments in patients with peripheral spondyloarthritis (SpA). We retrospectively studied 27 SpA patients, in whom an anti-TNF agent was added for active peripheral arthritis with knee synovitis refractory to DMARDs and treatment with low-dose oral corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular (IA) corticosteroids. As response of knee synovitis, were considered the absence of swelling, tenderness, and decreased range of movement in the clinical examination, after 4 months of anti-TNF therapy. In twenty-four (88.9%) of the patients there was response of knee synovitis. No statistical differences in gender (P = 0.53), age (P = 0.88), disease subtype (P = 0.22), and pattern of arthritis (P = 0.20) between knee synovitis responders and nonresponders were found. Fourteen patients managed to stop DMARD therapy and six, all of whom were initially on DMARDs combination, to decrease the number of DMARDs to one, maintaining simultaneously the response of knee synovitis. Our results imply a beneficial effect of adjunctive anti-TNF therapy on knee synovitis not responding to DMARDs and other standard treatments in patients with peripheral SpA.

Rituximab Treatment for Spondyloarthritis. A Nationwide Series: Data from the AIR Registry of the French Society of Rheumatology

To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry. All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction. Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1-40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn's disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1-5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral). In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress

As a number of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration, increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The safety of long-term therapy of RA is very important as patients with RA are usually treated for two or more decades. This experimental overview is focused on some promising substances and their combinations with the standard antirheumatic drug – methotrexate (Mtx) for treatment of rheumatoid arthritis. The adjuvant arthritis model in Lewis rats was used for evaluation of antiinflammatory efficacy of the substances evaluated. Mtx was administered in the oral dose of 0.3 mg/kg b.w. twice a week. Natural and synthetic antioxidants were administered in the daily oral dose of 20 mg/kg b.w for coenzyme Q10 (CoQ10), 150 mg/kg b.w for carnosine (Carn), 15 mg/kg b.w. for stobadine dipalmitate (Stb) and its derivative SMe1.2HCl (SMe1), and 30 mg/kg b.w. for pinosylvin (Pin) or pterostilbene (Pte). Mtx in the oral dose of 0.4 mg/kg b.w. twice a week was combined with Pin in the oral daily dose of 50 mg/kg b.w. Clinical (hind paw volume – HPV), biochemical (activity of GGT in joint and level of TBARS in plasma), and immunological (IL-1 in plasma) parameters were assessed. Our results achieved with different antioxidants in monotherapies showed a reduction of oxidative stress in adjuvant arthritis independently of the chemical structure of the compounds. Pin was the most effective antioxidant tested in decreasing HPV. All combinations tested showed a higher efficacy in affecting biochemical or immunological parameters than Mtx administered in monotherapy. The findings showed the benefit of antioxidant compounds for their use in combination therapy with methotrexate.

Rheumatoid Arthritis in a North American Native Population: Longitudinal Followup and Comparison with a White Population

To describe differences in phenotype and outcomes in North American Native (NAN) patients with rheumatoid arthritis (RA) followed prospectively and compared to white patients with RA. Patients from a single academic center were followed over 20 years using a custom database. Data included diagnoses, year of disease onset, ethnicity, modified Health Assessment Questionnaire (mHAQ) score, patient and physician global scores, tender and swollen joint counts, treatment, serology, and erythrocyte sedimentation rate (ESR). Records of all white (n = 1315) and NAN (n = 481) patients with RA were abstracted. Cumulative treatment data and clinical measures were compared. Disease duration was longer in white patients compared to NAN patients (16 +/- 11 vs 14 +/- 10 years, respectively; p = 0.03). Onset age was 34 years for NAN patients and 43 years for white patients (p < 0.001). NAN patients were more frequently positive for rheumatoid factor (89% vs 74%; p < 0.001) and antinuclear antibody (57% vs 21%; p < 0.001). Although mean tender joint counts and swollen joint counts were similar, NAN patients had higher Lansbury scores (weighted joint count; 66.5 vs 49.7; p < 0.001), mHAQ scores (1.1 vs 0.9; p = 0.001), and ESR (31 vs 25 mm/h; p < 0.012). NAN patients had more frequent knee (53% vs 34%; p < 0.001) and elbow (62% vs 48%; p = 0.007) involvement. Compared to white patients, NAN patients took a higher lifetime number of disease-modifying antirheumatic drugs (3.2 +/- 1.9 vs 2.2 +/- 1.7; p < 0.001), had more combination therapy (38% vs 29%; p = 0.002), and had more frequent prednisone use (55% vs 39%; p < 0.001). Compared to white patients, NAN patients with RA develop disease earlier, are more frequently seropositive, have greater large joint involvement, and greater disease burden, although treatment is more aggressive. These differences are present early and persist throughout the disease course.

Efficacy of intraarticular infliximab in patients with chronic or recurrent gonarthritis: A clinical randomized trial

To evaluate the efficacy and safety of intraarticular infliximab compared with intraarticular methylprednisolone in patients with gonarthritis. In 23 patients with recurrent gonarthritis despite previous intraarticular corticosteroid therapy, a total of 41 intraarticular injections (20 infliximab and 21 methylprednisolone) were performed in 28 knees. Initial therapy was randomly assigned, and crossover therapy was eligible within 3 months. The clinical effect was assessed during 6 months of followup. The primary outcome was event-free survival, defined as the time after treatment until local retreatment was performed and/or nonimprovement of the knee joint score. Adverse effects were recorded during followup. All patients treated with intraarticular infliximab had an insufficient response. In contrast, 8 of the 21 intraarticular methylprednisolone injections were effective (P = 0.004). Between groups, no differences in the patients' age, disease duration, number of disease-modifying antirheumatic drugs, or previous intraarticular methylprednisolone were observed. Reported adverse effects were not related to therapy. Treatment with intraarticular infliximab injection was not effective in patients with a chronically inflamed knee joint. Intraarticular injection with methylprednisolone was superior despite previous intraarticular corticosteroid therapy. Further investigation is needed to provide these patients with a better alternative.

Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis

To study the association of the presence of fibromyalgia (FM) with the Disease Activity Score in 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study Short Form 36 (SF-36) health survey in patients with rheumatoid arthritis (RA). A total of 270 outpatients with RA were enrolled in a prospective cross-sectional study. The patients underwent clinical evaluation and application of the HAQ and SF-36 questionnaires. Disease activity was evaluated using the DAS28 score. FM and RA diagnoses were made according to American College of Rheumatology criteria. The overall prevalence of FM was 13.4%. This group of patients had a higher prevalence of female sex, older mean age, higher functional class, and longer morning stiffness than patients with only RA. Mean +/- SD DAS28 scores were significantly higher in patients with RA and FM (5.36 +/- 0.99) than in patients with RA only (4.03 +/- 1.39; P < 0.001). In a multivariable linear regression analysis, FM was an important predictor of the DAS28 score, even after adjusting for the erythrocyte sedimentation rate, number of swollen joints, functional class, number of disease-modifying antirheumatic drugs currently in use, current dose of steroids, and articular erosions. HAQ and SF-36 scores were also worse in patients with RA and associated FM. FM is related to worse scores on the DAS28, HAQ, and SF-36 in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 score because it is related to higher scores independently of objective evidence of RA activity.

Discriminant validity, responsiveness and reliability of the rheumatoid arthritis-specific Work Productivity Survey (WPS-RA)

IntroductionThe rheumatoid arthritis-specific Work Productivity Survey (WPS-RA) measures the impact of rheumatoid arthritis (RA) and treatment on patient productivity within and outside the home. It contains nine questions addressing employment status, productivity within and outside the home, and daily activities. The objective of this paper was to evaluate the discriminant validity, responsiveness, and reliability of the WPS-RA in patients with active RA.MethodsTwo hundred twenty subjects (mean age was 53.8 years, 83.6% were female, mean disease duration was 9.54 years, mean number of disease-modifying anti-rheumatic drugs failed was 2, and 38.6% were employed outside the home) in a phase III, 24-week, double-blind, placebo-controlled trial completed the WPS-RA at baseline and every 4 weeks until withdrawal/study completion. Validity was evaluated via known groups using baseline data (first and third quartiles of subjects' Health Assessment Questionnaire – Disability Index [HAQ-DI] scores and Short Form-36 health survey [SF-36] scores). To evaluate responsiveness, mean changes in WPS-RA at week 24 were compared between American College of Rheumatology 20% improvement criteria (ACR20) (or HAQ-DI) responders and non-responders. Standardized response mean (SRM) was also used to quantify responsiveness. All group comparisons were conducted using a non-parametric bootstrap-t method.ResultsSubjects with lower HAQ-DI or SF-36 scores generally had statistically greater RA-associated losses in productivity within and outside the home compared with subjects with higher scores (25 of 32 evaluations were statistically significant). Smallest differences between groupswere seen in work absenteeism and days with outside help. At week 24, ACR20 and HAQ-DI responders reported large improvements in productivity within and outside the home; non-responders reported mainly a worsening in productivity (P ≤ 0.05). Effect size for productivity changes in ACR20 or HAQ-DI responders was moderate to large for six out of eight items (SRM = 0.48 to 1.12). The effect size was small for work absenteeism and days with outside help. (SRM = 0.4 and 0.24, respectively). In non-responders, the magnitude of change was negligible (SRM < 0.1) or small (SRM < 0.3).ConclusionsThe WPS-RA has demonstrated properties of discriminative validity, reliability, and responsiveness for the measurement of productivity within and outside the home in subjects with active RA.

The impact of anti‐tumour necrosis factor therapy for rheumatoid arthritis on the use of other drugs and hospital resources in a pragmatic setting

Anti-tumour necrosis factor (anti-TNF) therapy has been an important development for the treatment of rheumatoid arthritis (RA) but the impact of its delivery on hospital resources in still emerging. We audited the effect of starting anti-TNF on the use of other anti-rheumatic therapies and hospital resources in a routine secondary care setting. A retrospective study of resource use before and after anti-TNF was conducted. Hospital records of 54 RA patients were studied and data taken from the time of commencing anti-TNF to 1 October 2004 and an equal time period prior to commencing anti-TNF. Identical data were collected for 54 controls not on anti-TNF. Relevant figures were extrapolated to per annum rates. Results were analysed using two-factor ANOVAs comparing the pre- versus post-anti-TNF period. Cases on intravenous (IV) versus subcutaneous (SC) anti-TNF were also compared in separate ANOVAs. Mean duration of anti-TNF therapy was 17.04 months (range 3.60-42.36). Mean pre- and 3-months post-anti-TNF Disease Activity Scores (DAS28) were 6.93 and 3.88, respectively. Cases were more likely than controls to be on oral prednisolone pre- and post-anti-TNF. Methylprednisolone requirement, number of disease-modifying anti-rheumatic drugs (DMARDs), telephone helpline contacts and duration as an inpatient reduced significantly post-anti-TNF. Day case admissions increased but outpatient appointments decreased only in cases on IV anti-TNF. In a pragmatic setting, anti-TNF therapy led to reduced need for steroid injections and other DMARDs, as well as reductions in use of several hospital resources. Wider replication of these findings will be important for planning delivery.

Predictors of response to anti-TNF- therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register

Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted. To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA. The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression. 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission. These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.

Outcome of late-onset rheumatoid arthritis

The objective of this study was to determine possible differences in the outcome of patients with rheumatoid arthritis (RA) with disease onset early and late in life. As part of a broader outcome study of RA which included patients seen in the division of Rheumatology of Hospital Universitario Marqués de Valdecilla of Santander, Cantabria (Northern Spain) with disease duration between 2 and 7 years, we selected patients with an age at disease onset of <or=45 or >or=65 years. The medical records of all eligible patients were reviewed for relevant clinical and laboratory variables; the patients were then further evaluated for disease activity using biological tests and joint indices such as joint counts and Thompson's Index, functional capacity using the American College of Rheumatology (ACR) functional classification (ACR-FC) and the modified Health Assessment Questionnaire (M-HAQ), and anatomical damage using the number of joint damage (NJD) and radiographs read by the Sharp's scoring method for joint erosion (JE), joint narrowing (JN), and overall. Patients in both subsets were then compared. For the multivariable analyses all patients in the original larger cohort were included, so that age could be used as a continuous variable and the power of the analyses could increase; 31 younger (mean age+/-SD: 36+/-7 years) and 35 older (73+/-6 years) patients were available for assessment. No differences in disease duration and gender distribution were observed. Likewise, both subsets had similar levels of disease activity, both articular indices, and biological markers. In contrast, elderly patients showed more functional limitations as per the M-HAQ [median (interquartile range): 0.4 (0.13-1.2) vs 0.13 (0-0.6), p=0.007] and greater anatomical damage as per the NJD [median (interquartile range): 2 (0-4) and 0 (0-2), respectively, p=0.04] and the JE, JN, and total Sharp Index score (p=0.001, 0.02, and 0.001, respectively). Although older patients took fewer disease-modifying antirheumatic drugs (DMARD) and combined DMARD treatments (2.5+/-1.4 vs 1.9+/-1.3, p=0.05 and 0.8+/-1.1 vs 0.3+/-0.6, p=0.01, respectively), multivariable analysis demonstrated an independent association between age at disease onset and the number of DMARD and functional and anatomical decline. Late-onset RA does not present a better prognosis than the early-onset form of the disease. At the very least the disease is comparable between both patient groups. However, disease compounded by age-associated factors may in fact have a worse prognosis late than early in life.

Quality-of-Life Considerations With Respect to Arthritis and Nonsteroidal Anti-inflammatory Drugs

This article first presents a hierarchical general quality-of-life framework, beginning with global “outcome” and progressing through dimensions, subdimensions, components, and finally to specific variables. Second, the Health Assessment Questionnaire (HAQ) is described as an example of a set of instruments designed to assess such a framework. A simple visual analog scale, which was incorporated into the HAQ in 1980 and which ranks the status of health from “very poor” to “very well,” has been shown to correlate strongly with traditional quality-of-life instruments, such as the Torrance “Feeling Thermometer.” Finally, the requirement for a side-effect index to assess quality of life related to different drug therapies is discussed. Comparative drug adverse event profiles are highlighted, a side-effect index presented, and some preliminary results and conclusions outlined. With drugs used for the treatment of rheumatic diseases, adverse events have been shown to vary widely. Indeed, the differences in side-effects are often 2–3-fold between drugs of the same class. Furthermore, the incidence of adverse events related to the use of many nonsteroidal anti-inflammatory drugs has been shown to be greater than that seen with a number of disease-modifying antirheumatic drugs.

Clinically important drug interactions with disease-modifying antirheumatic drugs.

Rheumatic diseases are mostly chronic in nature and often require long term drug treatment. An increasing number of disease-modifying antirheumatic drugs (DMARDs) are used earlier in the course of disease and increasingly in combination with each other. Often there is comorbidity with ensuing pharmacotherapy, especially in the elderly, and therefore the risk of unwanted drug interactions increases. Awareness of these interactions is important in order to either avoid or manage them. Antimalarials, gold, penicillamine (D-penicillamine), sulfasalazine and azathioprine have few clinically important drug interactions. The renal excretion of the antifolate methotrexate is affected by drugs that influence kidney function. This is of particular importance in patients with compromised renal function, e.g. the elderly. Other drugs with influence on folate metabolism, such as trimethoprim, should not be given concomitantly. Cyclosporin is an agent recently introduced in rheumatological practice, and shows a myriad of clinically significant drug interactions mainly based on interference with its metabolic degradation by cytochrome P450 3A, leading to increased or decreased blood concentrations and toxicity or lack of effect. Although most of these interactions with cyclosporin are described in organ transplant patients, they may apply to rheumatological practice as well.