Time to disease-modifying antirheumatic drug treatment in rheumatoid arthritis and its predictors: a national, multicenter, retrospective cohort.

OBJECTIVE: To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors. METHODS: A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis. Time to each component of the care pathway was estimated. Multivariable modeling was used to determine predictors of early treatment using 12 preselected variables available in the clinical charts. Bootstrapping was used to validate the model. RESULTS: Within 6 months from symptom onset, 41% (95% CI 36%-46%) of patients were treated with DMARD. The median time to treatment was 8.4 (interquartile range 3.8-24) months. Events preceding rheumatology referral accounted for 78.1% of the time to treatment. The most prominent predictor of increased time to treatment was a concomitant musculoskeletal condition, such as osteoarthritis or fibromyalgia. The significance of other variables was less consistent across the models investigated. Included variables accounted for 0.69 ± 0.03 of the variability in the model. CONCLUSION: Fewer than 50% of patients with RA are treated with DMARD within 6 months from symptom onset. Time to referral to rheumatology represents the greatest component delay to treatment. Concomitant musculoskeletal condition was the most prominent predictor of delayed initiation of DMARD. Implications of these and other findings warrant further investigation.

Early management of newly diagnosed rheumatoid arthritis by Canadian rheumatologists: a national, multicenter, retrospective cohort.

OBJECTIVE: To describe early rheumatologic management for newly diagnosed rheumatoid arthritis (RA) in Canada. METHODS: A retrospective cohort of 339 randomly selected patients with RA diagnosed from 2001-2003 from 18 rheumatology practices was audited between 2005-2007. RESULTS: The most frequent initial disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.5%) and methotrexate (40.1%). Initial therapy with multiple DMARD (15.6%) or single DMARD and corticosteroid combinations (30.7%) was infrequent. Formal assessment measures were noted infrequently, including the Health Assessment Questionnaire (34.6%) and Disease Activity Score for 28 joints (8.9%). CONCLUSION: Initial pharmacotherapy is consistent with guidelines from the period. The infrequent reporting of multiple DMARD combinations and formal assessment measures has implications for current clinical management and warrants contemporary reassessment.

Relative urgency for referral from primary care to rheumatologists: the Priority Referral Score.

OBJECTIVE: Timely access to rheumatology consultation is fundamental to appropriate and effective management of patients with musculoskeletal and autoimmune diseases. Yet, for a variety of reasons, limited and delayed access is commonplace. Moreover, information exchange for referral is often inadequate or poorly communicated. The objective of this work was to improve referral from primary care to rheumatology by formulating and testing a clinically coherent, reliable, and non-diagnosis-dependent Priority Referral Score (PRS). METHODS: Using a deliberative process, a clinical panel of 10 primary care providers (PCPs) and rheumatology specialists reviewed clinical case scenarios and engaged in a highly iterative process to develop criteria, definitions, and weights for the PRS, a linear 100-point scale to rate the relative urgency of referral. Following tool formulation, clinicians uninvolved with the process tested the PRS against their clinical judgment. RESULTS: The PRS comprises 8 criteria, with 2-4 levels for each criterion, and each having a weight generated through conjoint analysis, which forced choices around the comparative urgency of all of the criteria and levels. The PRS showed a strong correlation between clinical rankings of rheumatologists and PCPs in both the deliberative panel, and the physicians subsequently involved in the testing of the PRS. CONCLUSION: No standardized priority-setting criteria are available for the full range of primary care referrals to rheumatologists. The PRS had face value with panelists and provided acceptable interrater and intrarater reliability when tested with other rheumatologists and PCPs. Pilot testing with other clinicians and in other settings is justified and prerequisite to use in clinical practice.

The development of inflammatory arthritis and other rheumatic diseases following stem cell transplantation.

OBJECTIVES: Despite the use of stem cell transplantation (SCT) to treat inflammatory arthritis and other rheumatic diseases, case reports of the paradoxical development of these diseases after SCT are appearing. Three cases of inflammatory arthritis developing after SCT were seen at our institution, leading to a literature review to determine the association between SCT and the de novo development of rheumatic conditions. METHODS: Using PubMed and manual searches of references from pertinent articles, the literature pertaining to the onset of rheumatic conditions following SCT was identified. RESULTS: Case reports detailing the onset of rheumatoid arthritis, HLA-B27-related spondyloarthropathy, psoriatic arthritis, systemic lupus erythematosus, vasculitis, eosinophilic fasciitis, antiphospholipid antibody syndrome, as well as polyarthritis related to intercedent viral infection were identified. Failure of transmission of autoimmune disease from donor to recipient in 2 case reports is also summarized. CONCLUSIONS: The incidence of rheumatic disease development after SCT is unknown, and reported cases may simply reflect those patients who were predisposed to disease development in the first place. However, immunologic manipulation during the SCT process raises the question of whether there is an increased propensity to develop autoimmune disease posttransplant. Clinical vigilance in the recognition of phenotypic changes and clinical events occurring after SCT which may represent new autoimmune phenomena is required.

Priority-setting tools for rheumatology disease referrals: a review of the literature.

As part of a larger body of work to develop a rheumatology priority referral score, a literature review was conducted. The objective of the literature review was to identify preexisting priority-setting, triage, and referral tools/scales developed to guide referrals from primary care to specialist care/consultation usually provided by a rheumatologist. Using a combination of database, citation, Internet, and hand-searching, 20 papers were identified that related to referral prioritization in three areas: rheumatoid arthritis (RA; 5), musculoskeletal (MSK) diseases other than RA (3), and MSK diseases in general (12). No single set of priority-setting criteria was identified for rheumatologic disorders across the spectrum of patients who may be referred from primary care providers (PCPs) to rheumatologists. There appears to be more congruence on conditions at either end of the urgency spectrum with conditions such as suspected cranial arteritis or systemic vasculitis deemed to be emergency referrals and fibromyalgia and other soft-tissue syndromes deemed to be more routine referrals. Between these two extremes, there is a divergence of opinion about urgency and few papers on the issue. The exception to this is referral for early RA for which several criteria have been established. Despite the inherent complexities in developing a tool to prioritize patients referred by PCPs to rheumatologists, there are compelling reasons to proceed. With the aging of the population, the number of patients being referred to rheumatologists is expected to increase. With pharmaceutical advances, there are demonstrable benefits in early referral for some conditions. These trends have led to increased pressure on scarce rheumatological human resources. A tool to prioritize referrals is a critical component of improving access and the referral process.

Rapid responses to anakinra in patients with refractory adult-onset Still's disease.

OBJECTIVE: To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept. METHODS: Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated. RESULTS: The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal 20,000/mm(3) with prominent neutrophilia, the CRP level rose to >200 mg/liter, and the ferritin level rose to >3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm(3), the CRP level fell to <3 mg/liter, and the ferritin level fell to <300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported. CONCLUSION: Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.

A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.

OBJECTIVE: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS: Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION: In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.

A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis.

OBJECTIVE: To determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Pamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized double-blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of > or = 4 or morning stiffness of > or = 45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and percentage of patients achieving a reduction of > or = 25% in the BASDAI. Outcome assessments were done at -2, 0, 12, and 24 weeks, and analysis was by intent to treat. RESULTS: Eighty-four AS patients (67 men and 17 women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60-mg group and by 0.93 (15%) in the 10-mg group (P = 0.002). Significantly greater reductions in the 60-mg group were also noted for the BASFI (P < 0.001), BASGI (P = 0.01), and BASMI (P = 0.03). Significantly more patients achieved a reduction of > or = 25% in the BASDAI in the 60-mg group versus the 10-mg group (63.4% versus 30.2%; P = 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10-mg group and 3 (7.3%) from the 60-mg group (P NS). Adverse events were confined to transient arthralgias/myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60-mg and 10-mg groups, respectively (P NS). CONCLUSION: Pamidronate has dose-dependent therapeutic properties in AS.