Faculty Bibliography

OBJECTIVE: To determine the frequency of liver function tests (LFT) abnormalities associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis (RA). METHODS: A retrospective chart review for demographic information, RA-specific history, medication history, complications of therapy, results of all available blood tests (specifically aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), albumin, creatinine), and liver biopsy reports was conducted for RA patients, who were currently using or have used MTX in the past. RESULTS: A total of 2791 LFTs were performed among 182 RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT evaluations demonstrated no abnormal results, compared with 30 patients (16.5%) who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients with at least one LFT abnormality (73.3%) continued treatment despite the elevation without further evaluation or change in therapy, and subsequent LFT assessments were within normal limits. 128 patients (70.3%) remained on MTX at the time of our study. The most common reason for discontinuation was inadequate response. CONCLUSIONS: MTX appears to be associated with very few clinically significant hepatic side effects. In view of these data, consideration as to revision of the current MTX monitoring guidelines in the direction of less frequent monitoring, especially in patients with no risk factors for liver disease, may be considered.

OBJECTIVE: To analyse patients with rheumatoid arthritis, treated with methotrexate in a weekly academic rheumatology clinic over 13 years, for continuation of courses and reasons for discontinuation. METHODS: All 248 patients with an analysable longitudinal course who took methotrexate in standard care between 1990 and 2003 were studied. Continuation of courses was analysed using life tables. All abnormal and severely abnormal values for aspartate aminotransferase (AST) >40 U/l, >80 U/l, albumin <35 g/l, <30 g/l, white blood cell (WBC) count <4.0 x 10(9)/l, <3.0 x 10(9)/l, and platelet count <150 x 10(9)/l, <100 x 10(9)/l, were identified. Responses of the clinician and subsequent laboratory values were reviewed. RESULTS: Over 1007 person-years, the probability of continuing methotrexate over five years was 79% (95% confidence interval, 72% to 84%). Severe laboratory abnormalities occurred in 2.9 per 100 person-years, specifically 0.9 for AST >80 U/l, 1.1 for albumin <30 g/l, 0.7 for WBC <3.0 x 10(9)/l, and 0.3 for platelets <100 x 10(9)/l. No severe laboratory abnormality progressed to further severity or clinical disease. Permanent discontinuations of methotrexate occurred in 46 patients (19%), 26 (10% of all patients) for adverse effects, 15 (32.6%) for inefficacy; only two discontinuations resulted from laboratory abnormalities, both of WBC, possibly from other sources. CONCLUSIONS: Methotrexate was associated with a high rate of continuation, and few clinically significant laboratory abnormalities. Discontinuation primarily reflected clinical rather than laboratory findings. Vigilance for methotrexate toxicity is required but methotrexate appears among the safest treatments for rheumatoid arthritis

OBJECTIVE: To compare the level of morning stiffness in a cohort of patients with early rheumatoid arthritis (RA), assessed on a self-report questionnaire, to levels of patient self-report scores and clinical and laboratory variables. METHODS: A total of 337 patients with recent onset RA since 1998 were assessed for tender and swollen joint counts, erythrocyte sedimentation rate (ESR), physician global assessment, and radiographs of the hands and feet, as well as Multidimensional Health Assessment Questionnaire (MDHAQ) scores for functional disability, pain, fatigue, global status, morning stiffness, and number of symptoms. Regression models were used to estimate possible associations between these variables and morning stiffness. RESULTS: At study entry, 70 patients (21%) reported no morning stiffness, 52 (15%) reported morning stiffness < 15 minutes, 52 (15%) for 16-59 minutes, and 163 (49%) for >/= 1 one hour. At baseline and in longitudinal analyses, morning stiffness was significantly associated with functional disability scores on the MDHAQ and with other patient self-report data, and was associated at lower levels with swollen and tender joint counts and erythrocyte sedimentation rate (ESR). CONCLUSION: The degree of morning stiffness appears to reflect functional disability and pain more than traditional markers of inflammation such as joint counts and ESR in patients with early RA. Inclusion of morning stiffness as a marker of inflammatory activity in classification criteria for RA, inclusion criteria for most clinical trials in RA, and RA remission criteria, may be open to reassessment

Hughes-Stovin syndrome (HSS) is a rare clinical disorder, which has been described as the presence of pulmonary artery aneurysm in the setting of systemic thrombosis. The term "Incomplete Behcet's Disease" has also been used to describe this syndrome due to the clinical and histopathological similarities between Behcet's disease and HSS. Indeed, pulmonary involvement can be indistinguishable between these two conditions of unknown pathophysiology. We describe an HSS patient who presented with a recurrent pulmonary artery aneurysm, review the clinical and pathological manifestations of HSS, discuss its similarities to Behcet's disease, and finally make the argument that HSS is in fact Behcet's disease.

OBJECTIVE: To determine what monitoring protocols rheumatologists use to identify adverse events in rheumatoid arthritis (RA) patients treated with methotrexate (methotrexate), etanercept (etanercept), infliximab (infliximab), and anakinra (anakinra), how often rheumatologists encounter treatment-altering adverse events in their RA patients receiving these treatments, and how they feel about and comply with the current monitoring guidelines. METHODS: Three hundred ten physician members of the American College of Rheumatology (ACR) were notified by e-mail of a survey that was posted on our rheumatology Web site. Questions were closed-ended and multiple choice in format. RESULTS: One hundred twenty-three responses were received (40%). Most rheumatologists reported that they utilize the ACR recommended screening tests at baseline before methotrexate treatment is initiated. Seventy-nine percent reported that treatment-altering abnormalities had occurred in <5% of their methotrexate-treated RA patients, and 88% reported that such abnormalities had occurred in <10% of such patients, in the previous 3 years. Forty-one percent believed liver function monitoring guidelines need to be changed; 59% said they would agree with new guidelines that would include a recommendation for liver function monitoring every 3-4 months. Most rheumatologists were not aware of any guidelines for monitoring by blood tests in RA patients treated with biologic agents, yet the majority reported that they order blood tests before patients start these therapies and on followup. CONCLUSION: Our survey indicates that treatment-altering liver function abnormalities in methotrexate-treated RA patients are rare, and more than half of rheumatologists agree that a less stringent monitoring regimen should be considered. Rheumatologists and pharmaceutical companies might work together to develop guidelines for monitoring of patients treated with biologic agents

The two major advances over the 1990s in the treatment of rheumatoid arthritis (RA) were a shift in strategy from a 'pyramid', in which disease modifying anti-rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive use of DMARDs and widespread acceptance of methotrexate as the DMARD with the most long-term effectiveness and safety. Methotrexate courses are continued far longer than those of any other DMARD, an excellent indicator of greater effectiveness and safety. In one recent series, methotrexate was the first DMARD used in more than 80% of patients with RA. Studies which document the superiority of combinations of methotrexate with biological agents to methotrexate monotherapy select for only a minority of contemporary patients with RA who have severe disease activity and incomplete responses to methotrexate. In one locale, only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate directly with biological agents, the biological agents have greater efficacy in patients with very severe disease, but the best results are seen in patients who take a combination of methotrexate and biologic agents. These data establish that methotrexate is the anchor drug and probably should be the first DMARD used in the majority of patients with RA at this time

Several databases of patients with early rheumatoid arthritis (RA) have been established in the USA. The University of Tennessee at Memphis Cohort was organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset of < or = 6 months who met the 1958 American Rheumatism Association (ARA) criteria for at least probable RA. Two important observations from this database were that many patients seen within the first 6 months of meeting the criteria for probable RA have a self-limited rather than progressive disease, and that progressive disease is predicted by a high number of baseline swollen and tender joints. The National Institutes of Health (NIH) cohort of patients with peripheral synovitis for > or = 6 weeks but < 12 months in at least one peripheral joint was established in 1994. At the one-year follow-up, 45% of the patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated arthritis. The number of active joints, rather than meeting the criteria for RA, was the primary determinant of function and performance after one year. The Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or = 6 swollen and > or = 9 tender joints, and no previous treatment with disease modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the validity of self-report joint counts. American College of Rheumatology 20% improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57% of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of patients prior to the availability of biologic agents. The North American Cohort of Patients with Early RA (SONORA), which included patients with symptoms for > 3 but < 12 months, indicated that methotrexate (MTX) was the most frequently prescribed DMARD, being taken by more than half the patients. The Consortium for the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA repository has enrolled 123 African-American patients with early RA of less than 2 years' duration to analyze genetic and non-genetic factors associated with disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients with early RA (< 3 years) was established in 2001. In this registry, MTX was the first DMARD used in 83% of patients, and most patients would not meet the criteria for inclusion in recent clinical trials of biological agents. Further observation of recent cohorts of patients with early RA over the next decade should be informative regarding whether aggressive intervention strategies and new DMARDs and biologic agents lead to improved long-term outcomes

Pregnancy outcomes among patients who underwent total hip arthroplasty (THA) during their reproductive years were retrospectively evaluated. Twenty-one patients reported pregnancies after THA and 20 had live births. No prosthesis-related problems were reported. This is the first study that provides a patient-based assessment of pregnancy outcomes and delivery in women who underwent THA. The preliminary data suggest THA had no adverse effect on subsequent childbearing