Elevated DAS28-ESR in patients with rheumatoid arthritis who have comorbid fibromyalgia is associated more with tender joint counts than with patient global assessment or swollen joint counts: implications for assessment of inflammatory activity.

OBJECTIVES: More than 20% of rheumatoid arthritis (RA) patients have comorbid fibromyalgia (FM+), which may elevate DAS28-ESR (disease activity score 28-erythrocyte sedimentation rate) and other indices, resulting in challenges to assess inflammatory disease activity. Although several reports indicate that elevated patient global assessment (PATGL) may elevate DAS28 in the absence of inflammatory activity, less information is available concerning the other three components, tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR), to possibly elevate DAS28 in FM+ vs. FM- RA patients. METHODS: A PubMed search identified 14 reports which presented comparisons of DAS28-ESR and its four components in RA FM+ vs. FM- groups. Median DAS28, component arithmetic differences, pooled effect sizes and 95% confidence intervals were analysed in the FM+ vs. FM- groups. RESULTS: In FM+ vs. FM- groups, median DAS28 was 5.3 vs. 4.2, SJC 4.0 vs. 3.0, TJC 13.2 vs. 5.3, PATGL 61.6 vs. 39.9, ESR 26.3 vs. 26.5. DAS28-ESR was classified as "high" (>5.1) in 11/14 FM+ groups and "moderate" (3.2-5.1) in all 14 FM- groups. Effect sizes in FM+ vs. FM- groups for DAS28-ESR, SJC, TJC, PATGL, and ESR were large (≥0.8) in 10/14, 1/13, 12/13, 7/13, and 1/13 comparisons, respectively, and pooled effect sizes 0.84 (0.3, 1.4), 0.33 (-0.4, 1.0), 1.27 (0.01, 2.5), 0.91 (-0.6, 2.4), and 0.07 (-0.6, 0.7), respectively. CONCLUSIONS: DAS28-ESR is elevated significantly in FM+ vs. FM- RA patients; pooled effect sizes were highest for TJC, followed by PATGL, SJC and ESR. The findings appear relevant to response and remission criteria, treat-to-target, and general management of RA.

Satisfaction With a Virtual Learning Collaborative Aimed at Implementing Treat-to-Target in Rheumatoid Arthritis.

OBJECTIVE: Limited information is available concerning experiences of participants in a virtual learning collaborative (LC), and little qualitative data or participant feedback on how this format can be improved. One prior in-person LC in rheumatology successfully improved adherence with treat-to-target (TTT) for RA. We conducted a virtual LC on TTT and herein report on participant satisfaction. METHODS: We conducted a virtual LC with 18 rheumatology practices from across the United States during 2020 to 2021. The LC included a virtual kickoff meeting and monthly videoconferences, accompanied by data submission and feedback. At the conclusion of the LC, we surveyed the 45 LC participants concerning individual experience and satisfaction. RESULTS: All sites and 78% of participants responded to the surveys. The LC included small and large practices, 14 academic and 4 nonacademic, and respondents ranged in their roles: 24 physicians, 5 nurses or nurse practitioners, 3 administrators, and 3 other roles. Overall, 94% of respondents indicated they were either somewhat or very satisfied with the LC, and 94% said they would recommend a similar LC to a colleague. Aspects of the LC described as "very useful" included a kickoff meeting, intersite discussion, and monthly speakers; however, digital tools such as the Web site and meeting recordings were not found useful. CONCLUSIONS: Virtual LCs are feasible, and participants reported strong satisfaction. Virtual LCs were highly valued by rheumatologists, trainees, and their practice staffs. Potential topics were identified for future LCs that could improve the quality of care delivered to rheumatology patients.

Low socioeconomic status and patient questionnaires in osteoarthritis: challenges to a "biomedical model" and value of a complementary "biopsychosocial model".

Modern medical care is based largely on a paradigm known as a "biomedical model," in which "objective," high-technology biomarkers guide clinical care, and most health outcomes are determined by health professionals rather than individuals, using drugs as the primary therapy. The biomedical model is spectacularly effective in the acute care inpatient hospital, the setting for 95% of medical education and training, and to guide management of many chronic diseases, such as hypertension and diabetes, for which a "gold standard" biomarker is a major determinant of clinical decisions. This model also has contributed importantly to knowledge of biomarkers, biochemical and structural abnormalities in osteoarthritis (OA) and other rheumatic diseases. However, a biomedical model has many limitations in understanding the long-term course of OA and many chronic diseases in outpatient medicine, the setting of 95% of activities that determine long-term health outcomes. Patient self-report questionnaires provide the most informative data concerning OA patient status and changes in status, and more significant data in the prognosis of outcomes such as mortality than laboratory or radiographic measures. Furthermore, the incidence, prevalence, morbidity, and mortality of OA is considerably greater in individuals of low versus high socioeconomic status. These associations are not unique to OA, and are seen in many diseases, including comorbid conditions which are the acute causes of death in OA. Associations of low socioeconomic and poor health are explained only in small part by limited access to medical services, the conventional explanation. Strong evidence suggests that socioeconomic status is a surrogate marker for patient self-management, actions and environment, in addition to actions of health professionals, in the pathogenesis, course and outcomes of chronic diseases. These observations suggest the value of a complementary "biopsychosocial model" to better understand pathogenesis, principles of treatments, and outcomes in OA and other chronic diseases. Inclusion of clinical information from patient questionnaires and socioeconomic status variables in clinical and research settings could add new understanding of biomarkers and pain in OA for both basic and clinical investigators. Furthermore, the data indicate that poor physical function assessed on a self-report questionnaire might be regarded as an important reversible risk factor in public health and research agendas, for which the OA community might be strong advocates.

Patient questionnaires in osteoarthritis: what patients teach doctors about their osteoarthritis on a multidimensional health assessment questionnaire (MDHAQ) in clinical trials and clinical care.

A patient history generally provides the most important information in diagnosis and management of patients with most rheumatic diseases, including osteoarthritis (OA). Patient history components can be expressed as quantitative, structured, "scientific" data, rather than "subjective" narrative descriptions, using patient self-report questionnaires. The Western Ontario McMaster (WOMAC) questionnaire is used in all OA clinical trials, and the health assessment questionnaire (HAQ) in all rheumatoid arthritis (RA) clinical trials, as "disease-specific" questionnaires. However, both questionnaires include scores for physical function function and pain; physical function scores are correlated highly significantly at r=0.78 in both RA and OA patients, while WOMAC pain scores are correlated with HAQ visual analogue scale (VAS) pain scores at r=0.73 in OA and r=0.71 in RA. Therefore, the WOMAC and HAQ may be regarded as largely "generic" questionnaires, at least for people with arthritis. Since it is not feasible to ask patients with different diagnoses to complete different care questionnaires in busy clinical settings, a single multidimensional HAQ (MDHAQ), derived from the HAQ and largely similar and informative in all rheumatic diseases, has been used in all rheumatology patients in several settings. The MDHAQ also has been incorporated into two OA clinical trials, with virtually identical results to the WOMAC. In routine clinical care, MDHAQ scores have documented that the disease burden of OA is comparable to RA in terms of scores for pain, physical function, and RAPID3 (routine assessment of patient index data) an index of pain, function and patient global assessment. Further observations indicate capacity of the MDHAQ to recognise fibromyalgia similarly to formal fibromyalgia criteria, as well as the ineffectiveness of opioids in OA, and similar prevalence of depression and other psychological issues in OA to RA. These findings also illustrate the value of a database of MDHAQ data for retrospective analysis of serendipitous observations from routine clinical care.

Osteoarthritis is as severe as rheumatoid arthritis: evidence over 40 years according to the same measure in each disease.

Osteoarthritis (OA) may be associated with substantial work disability, morbidity, costs, and increased mortality rates, often similar to rheumatoid arthritis (RA), documented in many published reports over the last 4 decades. However, OA generally has been viewed as less severe than RA. This discrepancy may be explained in part by:a) RA may have been considerably more severe in the past, prior to effective therapies.b) most older individuals have radiographic joint damage, which often is not associated with clinical symptoms.c) RA is associated with abnormal laboratory tests, which are regarded as conveying greater significance than symptoms of pain and disability according to a "biomedical model," the dominant paradigm of modern medicine.d) Most reports of OA and RA have emphasised differences between the 2 diseases even beyond laboratory abnormalities in pathogenesis, physical findings, and imaging.e) Even pain and functional disability seen in both diseases are assessed using different patient self-report questionnaires, a WOMAC (Western Ontario McMaster Universities osteoarthritis index) in OA, and HAQ (health assessment questionnaire) in RA.An identical measure is required for optimal direct comparisons, which has been used in 8 studies performed between 1979 and 2019 at 8 sites in North America, Europe, and Australia. These studies were primarily based on retrospective analyses at sites which collected a patient questionnaire in routine clinical care by all patients at all visits to inform clinical decisions. A pain visual analogue scale (VAS) was higher in OA compared to RA in 11/12 patient groups, while physical function on a HAQ (health assessment questionnaire) or derivative MDHAQ (multidimensional HAQ) and RAPID3 (routine assessment of patient index data) were slightly higher in RA before 2013 and higher in OA in later reports. Furthermore, a study of population-based data from the 1978 US Health Interview Survey indicated similar levels of disability and earnings losses according to surrogate variables for OA and RA. Therefore, at least over the last 40 years, pain and functional disability in OA have appeared to be severe and similar to RA. These observations also-illustrate the potential value of using an identical patient questionnaire in all patients at all visits in routine care settings, analogous to using the same laboratory tests such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in all rheumatic diseases, and maintaining a database of the results for later analyses.

Assessment of pain and other patient symptoms in routine clinical care as quantitative, standardised, "scientific" data.

Pain is the most common basis for visits to a rheumatologist, and reduction of pain is a primary goal of clinical care. Pain is assessed optimally by the patient on a self-report questionnaire. In clinical trials and other clinical research concerning pain and pain relief, detailed questionnaires are generally completed by patients. However, in routine clinical care, pain is generally assessed only according to narrative descriptions by the physician, and only a minority of settings assess pain using a standard, quantitative measure. Accurate, standard, quantitative assessment of pain in routine care is easily assessed in all patients with all diagnoses on a 0-10 visual analogue scale (VAS), by asking each patient to complete a 2-page multidimensional health assessment questionnaire/routine assessment of patient index data 3 (MDHAQ/RAPID3) at all visits. The MDHAQ includes VAS for pain, patient global assessment, and fatigue, as well as a quantitative physical function scale, RAPID3, review of systems, and recent medical history. The questionnaire provides the doctor with a 10-15 second overview of medical history data that otherwise would require about 10-15 minutes of conversation, saving time for the doctor and patient to focus on the most prominent concerns for the visit. MDHAQ scores from patients with 10 different rheumatic diagnoses, and specific data indicating similarity of scores in patients with osteoarthritis versus rheumatoid arthritis on the same questionnaire, are presented to illustrate the value of the MDHAQ in routine care.

A RheuMetric physician checklist to quantitate levels of inflammation, damage and distress on 0-10 visual analogue scales.

A physician global assessment of patient status (DOCGL) was designed initially to quantitate inflammatory activity in rheumatoid arthritis (RA) clinical trials, in which patients are selected for high levels of activity. However, in patients seen in routine care with various diagnoses, and even in some RA patients selected for clinical trials, DOCGL also may be affected by joint damage and/or patient distress. To clarify DOCGL on a 0-10 visual analogue scale (VAS), 3 additional 0-10 VAS have been developed to record physician estimates of inflammation (DOCINF), damage (DOCDAM), and distress (DOCSTR) (such as fibromyalgia (FM)/depression). Results from 3 locales for these 4 VASs are summarised, including 478 initial-visit patients from Tennessee in 1996 to 2007, 197 initial-visit patients from Pennsylvania in 2008 to 2012, and a random visit of 739 patients from Illinois in 2014 to 2015. Highest DOCGL estimates were seen at the 3 sites in FM, followed by RA and osteoarthritis (OA), spondyloarthropathies (SpA), gout, and systemic lupus erythematosus (SLE). Highest DOCINF (inflammation) estimates were seen in RA and SpA, followed by gout, SLE, FM, and OA. Highest DOCDAM (damage) estimates were in OA, followed by RA, SpA, gout, SLE and FM. Highest DOCSTR (distress) estimates were in FM, followed by OA, RA, SpA, SLE, and gout. In the 2 earlier series, DOCDAM was considerably higher than DOCINF only in OA, and lower in the other diagnoses, although within 50% of DOCINF. In more recent patients from Illinois, mean DOCDAM was higher than DOCINF in all 6 diagnoses. The 0-10 physician VASs depict the expertise of a rheumatologist to distinguish between inflammation, damage and distress in an individual patient and rate levels as quantitative data beyond narrative descriptions. These VASs appear informative for rheumatology care, documentation, and research.

Pain and other self-report scores in patients with osteoarthritis indicate generally similar disease burden to patients with rheumatoid arthritis.

OBJECTIVES: Osteoarthritis (OA) is regarded as a less severe form of arthritis than rheumatoid arthritis (RA) by health professionals and the general public, based largely on laboratory findings of autoantibodies and acute phase reactants. Relatively few studies have reported data from the patient's perspective to compare directly OA versus RA using the same self-report questionnaire measure. We aimed to summarise reports that compare OA versus RA patient pain scores and other indicators of disease burden according to the same self-report questionnaire. METHODS: A retrospective review identified 5 published reports at 8 rheumatology sites in 4 countries from 1989 to 2017 in which patients with OA versus RA completed the same patient self-report questionnaire for pain and other variables. Most comparisons involved a health assessment questionnaire (HAQ) and derivative multidimensional HAQ (MDHAQ), which include physical function, pain visual analogue scale (VAS) and patient global assessment VAS. Other questionnaires were included in one or two reported studies. RESULTS: Mean or median pain VAS was in a similar range in OA versus RA, though somewhat higher in OA at 7 of 8 sites studied (included in 1989). Physical function and other scores also were in a similar range for RA versus OA. Evidence of higher scores for physical function in RA relative to OA in earlier than more recent studies was seen, although all studies indicated a clinically important disease burden in OA. CONCLUSIONS: OA presents a severe disease burden to patients, which appears similar to RA. The findings suggest revision of current clinical and public policy views concerning OA.

Electronic multidimensional health assessment questionnaire (eMDHAQ): past, present and future of a proposed single data management system for clinical care, research, quality improvement, and monitoring of long-term outcomes.

An MDHAQ/RAPID3 (multidimensional health assessment questionnaire/routine assessment of patient index data) was developed from the HAQ over 25 years, based on observations made from completion by every patient (with all diagnoses) at every routine rheumatology visit since 1980. Modification of the HAQ was viewed as similar to improving a laboratory test, with a primary focus on clinical value for diagnosis, prognosis, and/or management, as well as feasibility for minimal effect on clinical workflow. Rigorous attention, was also directed to validity, reliability, other methodologic and technological considerations, but after clinical value and feasibility were established. A longer "intake" MDHAQ was introduced for new patients to record a complete past medical history - illnesses, hospitalisations, surgeries, allergies, family history, social history and medications. MDHAQ scales not found on the HAQ record complex activities, sleep quality, anxiety, depression, self-report joint count, fatigue, symptom checklist, morning stiffness, exercise status, recent medical history, social history and demographic data within 2 pages on one sheet of paper. An electronic eMDHAQ/RAPID3 provides a similar platform to pool data from multiple sites. A patient may be offered a patient-administered, password-protected, secure, web site, to store the medical history completed on the eMDHAQ. This eMDHAQ would allow a patient to complete a single general medical history questionnaire rather than different intake questionnaires in different medical settings. The eMDHAQ would be available for updates and correction by the patient for future visits, regardless of electronic medical record (EMR). The eMDHAQ is designed to interface with an EMR using HL7 (health level seven) and SMART (Substitutable Medical Apps, Reusable Technology) on FHIR (Fast Healthcare Interoperability Resources), although implementation requires collaboration with the EMR vendor. Advanced features include reports for the physician formatted as a medical record note of past medical history for entry into any EMR without typing or dictation, and a periodic "tickler" function to monitor long-term outcomes with minimal effort of the physician and staff. Nonetheless, clinical use of an eMDHAQ should be guided primarily not by the latest technology, but by value and feasibility in clinical care, the same principles that guided development of the pencil-and-paper MDHAQ/RAPID3.

Electronic eRAPID3 (Routine Assessment of Patient Index Data): opportunities and complexities.

RAPID3 (routine assessment of patient index data) is an index found within a multi-dimensional health assessment questionnaire (MDHAQ) for routine clinical care, composed only of 3 self-report scores for physical function, pain, and patient global estimate, each scored 0-10, for a total of 0-30. RAPID3 is correlated significantly with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index), and distinguishes active from control treatments as efficiently as these indices in clinical trials involving adalimumab, abatacept, certolizumab, infliximab, and rituximab. Many versions of an electronic RAPID3 (eRAPID3) have been developed, which are incompatible with one another, as seen for electronic medical records (EMR). Therefore, opportunities are lost to pool data from many sites for advancement of patient care and outcomes. Interfaces for linkage to EMRs and pooling of data are available as Health Level Seven (HL7) standards, FHIR (Fast Health Interoperability Resources), and innovative open platforms like SMART (Substitutable Medical Apps, Reusable Technology), but many eRAPID3 versions do not have this capacity. RAPID3 scores may be elevated in many patients due to damage or distress, rather than, or in addition to, inflammation, a problem that also affects DAS28, CDAI, and all RA indices which include a patient global estimate, even if they include a formal joint count. A full MDHAQ, of which RAPID3 is a component, provides clues to the presence of damage, and/or distress and adds much further information, with no more work for the health professional and little more time for the patient. A RheuMetric physician checklist of global scores for inflammation, damage, and distress is also useful to recognise damage and/or distress, but not available with most available eRAPID3 versions. Many eRAPID3 versions also are limited by the absence of flowsheets to monitor scores over time, the absence of strategies to convey data to health professionals to improve care, and the absence of advanced features for patients and doctors which are available in some versions of an eRAPID3. It is recommended that eRAPID3 should include a full MDHAQ, RheuMetric checklist, a longitudinal flowsheet of scores, and a defined strategy for management of the data to be available to the physician for improved patient care, to enhance value and quantitative interpretation of RAPID3 scores.

Assessment of fatigue in routine care on a Multidimensional Health Assessment Questionnaire (MDHAQ): a cross-sectional study of associations with RAPID3 and other variables in different rheumatic diseases.

OBJECTIVES: To characterise associations of fatigue with other variables within a multidimensional health assessment questionnaire (MDHAQ) in routine care of patients with different rheumatic diagnoses. METHODS: All patients complete MDHAQ, which includes fatigue on a 0-10 visual analogue scale (VAS), and routine assessment of patient index data (RAPID3), a composite of function, pain, and patient global. Physicians complete a RheuMetric checklist which includes 4 VAS for overall global status (DOCGL), inflammation, damage, and distress. Median score for fatigue and other MDHAQ and RheuMetric scores were compared in 4 diagnosis groups: rheumatoid arthritis (RA), osteoarthritis (OA), systemic lupus erythematosus (SLE), and fibromyalgia (FM), using a Kruskall-Wallis test. Associations of fatigue with other variables were analysed using Spearman correlations and multivariate regressions. RESULTS: 612 patients were included: 173 RA, 199 with OA, 146 with SLE, and 94 with FM. Median fatigue was significantly higher in FM (7) than in RA (4), OA (5), and SLE (5). Fatigue was correlated significantly with all other MDHAQ scores, at higher levels in RA and SLE versus OA and FM. Fatigue was correlated significantly with DOCGL in RA, OA, SLE, but not FM. In multivariate analyses, fatigue scores were explained independently by higher pain and symptom number in RA; lower age and higher symptom number in OA; only higher pain in SLE; and none of the variables in FM. CONCLUSIONS: Fatigue is common in rheumatic diseases and strongly associated with higher pain and number of symptoms. The MDHAQ provides a useful tool to assess fatigue in clinical settings.

Clinical trials documenting the efficacy of low-dose glucocorticoids in rheumatoid arthritis.

Twelve clinical trials have documented that prednisone or prednisolone in doses of 10 mg/day or less is efficacious to improve function, maintain status and/or slow radiographic progression in patients with rheumatoid arthritis (RA). An early trial reported by de Andrade et al. [Ann Rheum Dis 1964;23:158-162] in 1964 indicated that 5 mg of prednisolone at night was preferred to 5 mg of prednisone in the morning. Harris et al. [J Rheumatol 1983;10:713-721] documented the efficacy of 5 mg/day of prednisone in a non-double-blind trial in 1983. Two important trials in the 1990s by Kirwan [N Engl J Med 1995;333:142-146] using 7.5 mg/day, and the COBRA study by Boers et al. [Lancet 1997;350:309-318] with step-down from 60 mg rapidly tapered to 5 mg/day led to strong advocacy of low-dose glucocorticoids. In 2002, the first Utrecht Study [Ann Intern Med 2002;136:1-12] indicated that 10 mg/day prednisone slowed radiographic progression, a finding confirmed and extended in 2005 by Svensson et al. [Arthritis Rheum 2005;52:3360-3370] with 7.5 mg/day, and Wassenberg et al. [Arthritis Rheum 2005;52:3371-3380] with 5 mg/day of prednisolone. In 2008, Buttgereit et al. [Lancet 2008;371:205-214] reported CAPRA-1, which documented that modified-release prednisone or prednisolone taken at bedtime led to lower morning stiffness and IL-6 levels compared to usual morning prednisone. In 2009, Pincus et al. [Ann Rheum Dis 2009;68:1715-1720] reported a withdrawal clinical trial, in which patients who took 3 mg/day were gradually withdrawn to placebo, and dropped out at a significantly higher rate than control patients who were 'withdrawn' to prednisone. In 2012, a second Utrecht Study [Ann Intern Med 2012;156:329-339], CAMERA-II, documented that 10 mg of prednisone added to a 'treat-to-target' strategy with methotrexate provided incremental slowing of radiographic progression. An Italian study of patients with early RA who received step-up disease-modifying antirheumatic drug therapy over 2 years plus prednisolone or not indicated higher rates of clinical remission and sustained remission associated with 7.5 mg/day of prednisolone [Arthritis Res Ther 2012; 14:R112]. The CAPRA-2 trial [Ann Rheum Dis 2013;72:204-210] documented that modified-release nighttime prednisone or prednisolone was significantly more efficacious than placebo. Taken together, these 12 clinical trials indicate that low-dose glucocorticoids prednisone or prednisolone provides symptomatic relief, improved functional status and slowing of radiographic progression for patients with RA. © 2014 S. Karger AG, Basel.

Circadian use of glucocorticoids in rheumatoid arthritis.

A clear temporal relationship exists in rheumatoid arthritis (RA) patients between increased nocturnal levels of pro-inflammatory cytokines, such as TNF-α and interleukin (IL)-6, pro-inflammatory hormones (i.e. melatonin, prolactin) and insufficient night production of the anti-inflammatory cortisol (circadian rhythm). Under long-standing chronic stress of disease, insufficient cortisol is available to inhibit an ongoing nocturnal immune/inflammatory reaction. Clinical RA symptoms follow the same circadian rhythm with highest morning severity. Chronotherapy with nighttime glucocorticoid (GC) availability optimizes the treatment of RA patients with low-dose GCs through more efficient targeting of mediators of the immune/inflammatory reaction during the night to be available on arising. Circadian use of low-dose, long-term prednisone, by using night-release formulations (ingested at 10 to 11 p.m.) especially in early RA patients, appears characterized by a significantly superior efficacy on decreasing morning stiffness and IL-6 serum levels, compared to conventional daytime immediate-release prednisone. Shift from medium-dose, immediate-release prednisone (over 7.5-10 mg/day) to night-release formulations GC low-dose, long-term chronotherapy requires a gradual passage, since the hypothalamic-pituitary-adrenal axis of the treated RA patients, potentially altered by a negative feedback induced by the medium/high daily exogenous GC administration, needs time to re-synchronize control of endogenous GC production into a circadian and more physiological nocturnal hormone availability/optimized efficacy.

The past versus the present, 1980-2004: reduction of mean initial low-dose, long-term glucocorticoid therapy in rheumatoid arthritis from 10.3 to 3.6 mg/day, concomitant with early methotrexate, with long-term effectiveness and safety of less than 5 mg/day.

Quantitative observations are presented concerning treatment with glucocorticoids of 308 patients with rheumatoid arthritis (RA) at a weekly academic rheumatology setting over 25 years from 1980 to 2004. A database of all visits included medications and multidimensional health assessment questionnaire scores for physical function, pain and routine assessment of patient index data (RAPID3; and a surrogate RAPID3-EST), completed by each patient at each visit in routine care. Over the 5-year periods of 1980-1984, 1985-1989, 1990-1994, 1995-1999 and 2000-2004, the mean initial prednisone daily dose declined from 10.3 to 6.5, 5.1, 4.1 and 3.6 mg/day, as initial doses were >5 mg/day in 49, 16, 7, 7 and 3% of patients, 5 mg/day in 51, 80, 70, 26 and 10%, and <5 mg/day in 0, 4, 23, 67 and 86%. Reduction of prednisone doses in the respective five-year periods was accompanied by increased and earlier use of methotrexate as the first disease-modifying antirheumatic drug (DMARD) in 10, 26, 57, 71 and 78%, and methotrexate treatment in 10, 26, 74, 82 and 92% of patients within the first year of disease. Higher methotrexate doses in the respective five-year periods were used after 1990, along with lower prednisone doses. Most patients were treated indefinitely with both low-dose prednisone and methotrexate; 80% continued both medications for more than 5 years. The primary adverse events were skin-thinning and bruising. New hypertension, diabetes and cataracts were seen in fewer than 10% of patients. While efficacy and safety cannot be analyzed definitively from observational data, the data suggest that many patients with RA might be treated effectively with weekly low-dose methotrexate along with initial and long-term, low-dose prednisone of <5 mg/day.

Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) underestimated in polyarticular psoriatic arthritis on the basis of limitations of clinical trials more than on limitations of MTX, as was seen in rheumatoid arthritis?

Clinical trials are the optimal method to establish efficacy of a drug versus placebo or another drug. Nonetheless, important limitations are seen, particularly in chronic diseases over long periods, although most are ignored. Pragmatic limitations of clinical trials include a relatively short observation period, suboptimal dosage schedules, suboptimal surrogate markers for long-term outcomes, statistically significant results which may not be clinically unimportant and vice versa. Even ideal clinical trials have intrinsic limitations, including the influence of design on results, data reported in groups which ignore individual variation, non-standard observer-dependent interpretation of a balance of efficacy and toxicity, and distortion of a "placebo effect." Limitations are seen in many clinical trials of methotrexate (MTX) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The first MTX clinical trial in rheumatology documented excellent efficacy in PsA, but frequent adverse events in 1964, explained by intravenous doses up to 150 kg. MTX was abandoned until the 1980s for RA, while gold salts and penicillamine were termed "remission-inducing," on the basis limitations of clinical trials. In the most recent MTX in PsA (MIPA) trial, all outcomes favoured MTX, but only patient and physician global estimates met the p<0.05 criterion. A conclusion of "no evidence for MTX improving synovitis" appears explained by insufficient statistical power, wide individual variation, no subsets, low doses, and other limitations. MTX appears less efficacious in PsA than RA, but may be underestimated in PsA, similar to historical problems in RA, resulting more from limitations of clinical trials than from limitations of MTX.

Routine Assessment of Patient Index Data (RAPID3) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Scores Yield Similar Information in 85 Korean Patients With Ankylosing Spondylitis Seen in Usual Clinical Care.

BACKGROUND: Disease-specific ankylosing spondylitis (AS) indices, including BASDAI (Bath AS Disease Activity Index), BASFI (Bath AS Functional Index), ASDAS (AS Disease Activity Score), and BASMI (Bath AS Metrology Index), are widely used in clinical trials and in some clinical settings, but not in most routine care. Laboratory tests usually are the only quantitative measures included in routine care of AS patients, but often are poorly informative. Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) is feasible and informative in many rheumatic diseases. OBJECTIVE: The aim of this study was to compare RAPID3 to BASDAI, BASFI, ASDAS, and BASMI in a cross-sectional analysis of 85 Korean AS patients collected in routine care. METHODS: MDHAQ/RAPID3, BASDAI, and BASFI were completed by patients, and ASDAS and BASMI assessed by health professionals. Indices and individual measures were compared using correlations, cross tabulations, scatter plots, and κ statistics. RESULTS: RAPID3 scores were correlated significantly with BASDAI (ρ = 0.82) and ASDAS-ESR (erythrocyte sedimentation rate) (ρ = 0.76), at levels similar to the correlation of BASDAI with ASDAS-ESR (ρ = 0.81). All 21 patients with BASDAI scores of 4 or greater, indicating active AS, were among 39 patients who had RAPID3 scores of greater than 12, indicating high severity, whereas 79% of 33 patients with ASDAS of greater than 1.3, indicating high activity, had RAPID3 high severity. CONCLUSIONS: RAPID3 gives similar information to BASDAI and ASDAS in AS patients, in this limited cross-sectional study from 1 setting. Ankylosing spondylitis-specific measures are needed for clinical trials, but poorly feasible in most busy clinical settings. The MDHAQ/RAPID3 offers pragmatic quantitative clinical assessment of AS patients in routine care.

Physician estimate of inflammation vs global assessment in explaining variations in swollen joint counts in rheumatoid arthritis patients.

Objective: To analyse patients with RA for inflammatory activity by physician estimate of global assessment (DOCGL) vs an estimate of inflammatory activity (DOCINF) to explain variation in the swollen joint count (SJC). Methods: Patients with RA were studied at routine care visits. Patients completed a multidimensional health assessment questionnaire (MDHAQ) and the physician completed a 28-joint count for swollen (SJC), tender (TJC) and deformed (DJC) joints and a RheuMetric checklist with a 0-10 DOCGL visual numeric scale (VNS) and 0-10 VNS estimates of inflammation (DOCINF), damage (DOCDAM) and patient distress (DOCSTR). The disease activity score in 28 joints with ESR (DAS28-ESR), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were calculated. Individual scores and RA indices were compared according to Spearman correlation coefficients and regression analyses. Results: A total of 104 unselected patients were included, with a median age and disease duration of 54.5 and 5 years, respectively. The median DAS28-ESR was 2.9 (Q1-Q3: 2.0-3.7), indicating low activity. DOCINF was correlated significantly with DOCGL (ρ = 0.775). Both DOCGL and DOCINF were correlated significantly with most other measures; correlations with DOCGL were generally higher than with DOCINF other than for SJC. In regression analyses, DOCINF was more explanatory of variation in SJC than DOCGL and other DAS28-ESR components. Conclusions: Variation in SJC is explained more by a 0-10 DOCINF VNS than the traditional DOCGL or any other measure in RA patients seen in routine care. DOCINF on a RheuMetric checklist can provide informative quantitative scores concerning inflammatory activity in RA patients monitored over long periods.