Faculty Bibliography

Rheumatologists generally use few quantitative measures in making clinical decisions. In the US, fewer than 10% use questionnaires in routine clinical care, and fewer than 15% perform a formal joint count at each visit. Patient questionnaires are the quantitative tools rheumatologists have to monitor their patients' health status and response to therapy. The health assessment questionnaire (HAQ) and its derivatives have been shown to be the best predictors of functional and work disability, costs, joint replacement surgery and mortality; they are as good as and usually better predictors than joint counts, radiographs and laboratory tests. The Brooklyn Outcomes of Arthritis Registry Database was initiated with the aim of collecting quantitative data using a multi-dimensional health assessment questionnire (MDHAQ) from all rheumatology patients seen as part of routine care, each and every time the patient was seen. Data that are feasible to collect in routine clinical care provide the only way to assess quantitatively how our patients are doing. If data are not collected and recorded, an opportunity is lost forever. If there is a reason for the visit, there is a reason to complete a questionnaire

The HAQ has become the pre-eminent patient questionnaire used in rheumatology. It is easily completed by patients, but not easily reviewed and scored in standard clinical care and has some minor psychometric limitations, as do all questionnaires. Modifications of the HAQ been made to facilitate use in standard care, particularly to include 8-10 activities of daily living, along with scores for pain and global status and other information on one side of one page for rapid review by the clinician. A patient questionnaire for standard care should be limited to 2 sides of 1 page, in a format amenable to 'eyeball' review by the clinician in 5 seconds or less. It can be scored formally in 15-20 seconds or less, and is useful in patients with all rheumatic diseases. The current version of a multi-dimensional HAQ (MDHAQ) includes scoring templates on the questionnaire to allow formal scoring in less than 15 seconds by a rheumatologist or an assistant, for possible entry onto a paper and/or computerized flow sheet. Various versions of the MDHAQ may also include a 'constant' region of physical function, pain and patient global status, and 'variable' regions of fatigue, morning stiffness, psychological distress, change in status, a review of systems, a rheumatoid arthritis disease activity self-report joint count (RADAI), review of recent health events, and review of medications. The MDHAQ can be used in the infrastructure of rheumatology care to include quantitative data in standard care of all patients with all rheumatic diseases

The purpose of this report is to provide suggested guidance concerning the monitoring of TNF blocker therapy. Since the completion of randomized trials, several new long-term safety concerns have arisen, involving mycobacterial and opportunistic infections, cytopenias, lymphoma, demyelinating disease, drug-induced lupus, congestive heart failure and hepatotoxicity. Since these serious events are rare, widespread post-marketing use and prolonged follow-up have been required to analyze their prevalence. Monitoring of TNF inhibitors is necessary to reassure physicians and patients of the continued efficacy and safety of these drugs. No published recommendations on monitoring are available. The clinician must weigh the potential clinical benefits of TNF inhibition against potential adverse effects. Patients should be evaluated carefully for the risk or presence of infection, tuberculosis and other serious adverse events by regular visits, careful clinical assessments, and an assiduous, high index of suspicion for these rare events. Tuberculin skin testing using PPD is recommended before starting treatment with any TNF inhibitor.

OBJECTIVE: To identify the proportion of patients fulfilling the inclusion criteria widely used in most clinical trials for rheumatoid arthritis (RA)--including the recent clinical trials of anti-Tumor Necrosis Factor alpha (TNFalpha) agents--in a Turkish cohort. METHODS: 186 consecutive RA patients attending a routine tertiary rheumatology clinic were evaluated in 2 groups: Early RA group (group E): 31 patients with a disease duration of < or = 3 years (mean: 1.9 +/- 0.9 years); late RA group (group L): 155 patients with a disease duration of > 3 years (mean: 13.3 +/- 8.6 years). Patients were evaluated according to 2 different sets of inclusion criteria: (i) The widely used common inclusion criteria for RA clinical studies, as outlined by Sokka and Pincus; (ii) the criteria of two major anti-TNF clinical studies, ERA and ATTRACT. RESULTS: No patients in group E, and 9 (6%) patients in group L fulfilled the common criteria used in clinical studies for RA. In group E, 28 patients had already been started on methotrexate; 2 patients were on sulphasalazine and one patient was on leflunomide. Nevertheless, even if the criterion for previous use of methotrexate was not applied patients did not fulfill the rest of the criteria of ERA study. In group L, 9 out of 155 patients (6%) met the criteria for the ATTRACT study. CONCLUSION: Only few patients met the widely used inclusion criteria for most RA clinical trials and the recent clinical trials of TNFalpha agents in this Turkish cohort. This may be explained by the milder disease activity in this geographical region, which further emphasizes the need to consider development of new criteria for inclusion in clinical trials.

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