Patient's experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis.

BACKGROUND: Despite the prominent position of methotrexate (MTX) in Rheumatoid Arthiris (RA) therapeutics, its real-world effectiveness may be influenced by a relative lack of tolerability or other side effects that physicians may not be aware of but that are bothersome to patients. The aim of this study is to identify suboptimal patient experience with MTX and to raise awareness for clinicians to identify opportunities to mitigate bothersome symptoms and side effects and optimize response to MTX. METHODS: We conducted a prospective, cross-sectional, online survey among RA patients who were members of Creakyjoints, a large arthritis patient community. Eligible participants must have recently initiated a new biologic, subcutaneous (SQ) MTX, or oral MTX in the last 12 months and were uniquely assigned to one of these 3 groups. Descriptive statistics were used to compare patient-reported side effects and tolerability related to MTX use in the 3 medication groups (SQ MTX, oral MTX, and biologic). RESULTS: A total of 382 (85 %) of 448 eligible patients completed the survey and were grouped as: biologic (n = 218), SQ MTX (n = 49), and oral MTX (n = 115). Demographics were mean standard deviation (SD) age 48 (10) years, 92 % white, 91 % women. Symptoms significantly more prevalent in the SQ and oral MTX groups included diarrhea, fatigue, malaise, and hair loss. Injection related pain was lower with SQ MTX compared to SQ biologics. Out of a total of 8 potential symptoms and side effects examined, higher dose MTX (> = 20 mg/week) was associated with a 2.26 (1.25-4.09) greater likelihood of more side effects referent to < =10 mg/week. CONCLUSION: Results from this real-world RA patient cohort suggest that MTX is accompanied by many patient-reported side effects and tolerability problems that may be under-recognized by physicians. These may impact both treatment satisfaction and medication adherence.

Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide.

INTRODUCTION: Potential hepatotoxicity associated with disease-modifying antirheumatic drugs (DMARDs) requires laboratory monitoring. In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined. METHODS: Patients with RA and PsA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) initiating DMARDs were identified. Abnormalities were identified when either was 1- or 2-fold times above the upper limits of normal (ULN). Odds ratios (OR) between MTX/LEF dose and elevated ALT/AST enzymes were estimated using generalised estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared with each individually. RESULTS: Elevated ALT/AST levels (>1x ULN) occurred in 22%, 17%, 31% and 14% of patients with RA receiving MTX, LEF, MTX+LEF or neither, respectively; elevations were 2.76-fold (95% CI 1.84 to 4.15) more likely in patients with PsA. Elevations >2x ULN occurred in 1-2% of patients on MTX or LEF monotherapy compared with 5% with the combination. After multivariable adjustment and compared with either monotherapy, the combination of MTX and LEF was associated with a greater risk according to MTX dose used as part of the combination: MTX 10-17.5 mg/week, OR 2.91 (95% CI 1.23 to 6.90); MTX > or =20 mg/week, OR 3.98 (95% CI 1.72 to 9.24). CONCLUSIONS: Abnormal ALT/AST levels developed in 14-35% of patients with RA or PsA initiating DMARD therapy. The risks were incrementally greater in those with PsA and in those receiving MTX (> or =10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.

Cost-effectiveness of multifaceted evidence implementation programs for the prevention of glucocorticoid-induced osteoporosis.

SUMMARY: Using a computer simulation model, we determined that an intervention aimed at improving the management of glucocorticoid-induced osteoporosis is likely to be cost-effective to third-party health insurers only if it focuses on individuals with very high fracture risk and the proportion of prescriptions for generic bisphosphonates increases substantially. INTRODUCTION: The purpose of this study is to determine whether an evidence implementation program (intervention) focused on increasing appropriate management of glucocorticoid-induced osteoporosis (GIOP) might be cost-effective compared with current practice (no intervention) from the perspective of a third-party health insurer. METHODS: We developed a Markov microsimulation model to determine the cost-effectiveness of the intervention. The hypothetical patient cohort was of current chronic glucocorticoid users 50-65 years old and 70% female. Model parameters were derived from published literature, and sensitivity analyses were performed. RESULTS: The intervention resulted in incremental cost-effectiveness ratios (ICERs) of $298,000 per quality adjusted life year (QALY) and $206,000 per hip fracture averted. If the cohort's baseline risk of fracture was increased by 50% (10-year cumulative incidence of hip fracture of 14%), the ICERs improved significantly: $105,000 per QALY and $137,000 per hip fracture averted. The ICERs improved significantly if the proportion of prescriptions for generic bisphosphonates was increased to 75%, with $113,000 per QALY and $77,900 per hip fracture averted. CONCLUSIONS: Evidence implementation programs for the management of GIOP are likely to be cost-effective to third-party health insurers only if they are targeted at individuals with a very high risk of fracture and the proportion of prescriptions for less expensive generic bisphosphonates increases substantially.

Usage of intra-articular corticosteroid injections for the treatment of juvenile idiopathic arthritis: a survey of pediatric rheumatologists in the United States and Canada.

OBJECTIVE: To characterize the current usage of intra-articular corticosteroid injections (IACI) by pediatric rheumatologists and the perceived disadvantages of and obstacles to IACI therapy. METHODS: We mailed a 32-item questionnaire to pediatric rheumatologists in the United States and Canada (n=201) to assess treatment strategies for the initial treatment of monoarthritis of the knee in juvenile idiopathic arthritis (JIA). Information regarding the usage of IACI for all patients with JIA and physicians' perceptions of IACI therapy was obtained. Respondents were dichotomized into those who performed frequent pediatric IACI (greater than 50 IACI in the last 12 months) and those who did not. RESULTS: One hundred and twenty-nine (64%) completed questionnaires were returned. IACI were recommended as one therapy for JIA by 99% of respondents, and 90% personally perform IACI. Frequent IACI were performed by 22%, and 15% had performed greater than 10 IACI in a single pediatric patient at one time. Those who did not perform frequent IACI were more likely to report concern about the pain of the procedure, the availability of nursing support, and their own comfort with performing the procedure; they were less likely to have performed greater than 20 pediatric IACI during fellowship training and evaluated fewer clinic patients per week. CONCLUSION: IACI are essentially universally recommended in the treatment regimen for JIA. However, there are differences in the usage of IACI among pediatric rheumatologists. The frequency of IACI use is associated with different perceptions of and training received in IACI therapy.

Incidence and risk factors for progressive multifocal leukoencephalopathy among patients with selected rheumatic diseases.

OBJECTIVE: To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists. METHODS: We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis. RESULTS: Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy. CONCLUSION: PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.