Rheumatoid Arthritis: Sokka T

Sokka T. · Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Clin Exp Rheumatol. · Pubmed #14969065 No free full text.

Abstract: The first Finnish early rheumatoid arthritis (RA) cohort was established in 1973-75 at the Rheumatism Foundation Hospital in Heinola, a hospital for rheumatic diseases only. Since then early RA cohorts for the purposes of longitudinal observation have been established at the Jyväskylä Central Hospital and Helsinki University Hospital. Furthermore, 199 patients with early RA were enrolled in a multicenter randomized controlled study in 1993-95. The primary observations from these cohorts are summarized in this essay.

Pincus T, Sokka T. · Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Clin Exp Rheumatol. · Pubmed #14969056 No free full text.

Abstract: Rheumatoid arthritis (RA) is not characterized by a single pathognomonic measure such as blood pressure in hypertension or cholesterol in hyperlipidemia, which can be used in the diagnosis, prognosis, and monitoring of patient status. Measures such as swollen joints and an elevated erythrocyte sedimentation rate are certainly valuable, but many individuals with abnormal values have conditions other than RA, and many people with RA may have favorable values for one or more of these measures. Therefore, the rheumatology community has developed indices of several measures, such as classification criteria, the disease activity score (DAS), and the ACR Core Data Set with 20%, 50% and 70% improvement (ACR 20, ACR 50, ACR 70) to classify and monitor patients with RA. While these indices have greatly advanced clinical research, databases for long-term observations, including those in early RA described in this Supplement, differ in 20-50% of included data, and the software platforms for these databases differ sufficiently to render it difficult to merge the data to compare one data set to another. It has been proposed that a uniform database for early arthritis clinical research could help advance clinical research in early arthritis. One example of such a database, termed a "standard protocol to evaluate rheumatoid arthritis" (SPERA), has been in use for almost two decades in one clinical site, and has proven valuable in a number of ways, including the demonstration of early radiographic damage, development of a 28-joint count, and documentation that patient questionnaire data are correlated significantly with laboratory, joint count and radiographic data, although questionnaire data are the strongest predictors of severe outcomes including work disability and premature mortality. The use of a uniform database in no way precludes the collection of additional data at particular centers including immunogenetic, serologic, or structural magnetic resonance imaging (MRI) data. However, the availability of an infrastructure of standard data in all RA databases would enhance clinical research in early RA.

Sokka T. · Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Clin Exp Rheumatol. · Pubmed #14969054 No free full text.

Abstract: Patients with rheumatoid arthritis (RA) are at risk of work disability from the very start of their symptoms. Prospective cohorts including patients with early RA show that 20-30% become permanently work disabled during the first 2-3 years of the disease. Risk factors for early work disability include a physically demanding job, older age, and lower educational level, as well as the level of functional disability in daily activities. Work disability accounts for a major fraction of the costs of RA both to the patient and to society. Improved work disability outcomes in RA may require attention to social, economic, and political issues, and broader physician and public education concerning RA, in addition to improved medical management of the disease.

Pincus T, Sokka T. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, 203 Oxford House, Box 5, Nashville, TN 37232-4500, USA. · Best Pract Res Clin Rheumatol. · Pubmed #12915156 No free full text.

Abstract: There is no single 'gold standard' quantitative measure to assess and monitor the clinical status in patients with rheumatoid arthritis (RA). Therefore, a variety of measures have been used in clinical research and clinical care, including laboratory tests, radiographic scores, formal joint counts, physical measures of functional status, global measures and patient self-report questionnaires. These measures may address disease activity, joint damage, both activity and damage, or long-term outcomes. Measures of disease activity, such as joint swelling, are reversible and are emphasized in clinical trials. However, activity measures may be improved over 5 years while measures of damage, such as radiographic score, indicate disease progression. Two quantitative indices which are widely used in clinical trials are the (1) American College of Rheumatology (ACR) Core Data Set, which includes swollen joint count, tender joint count, physician assessment of global status, acute-phase reactant-erythrocyte sedimentation rate or C-reactive protein, functional status, pain, patient estimate of global status, a radiograph in studies over 1 year or longer, and (2) the disease activity score(DAs), which includes a swollen joint count, tender joint count, acute-phase reactant, and patient assessment of global status. Randomized controlled clinical trials provide the optimal method to evaluate new therapies, by comparing a therapy with a placebo or another therapy without selecting patients for specific therapies. However, randomized trials in chronic diseases have important limitations, including a relatively short observation period, patient selection for inclusion and exclusion criteria, inflexible dosage schedules, influence of the design on results despite a control group, emphasis on group data while ignoring individual variation in treatment responses, non-standardized interpretation of adverse effects, and others. Therefore, clinical trials in RA must be supplemented by long-term observational studies to assess results of therapy in regard to long-term outcomes such as work disability, joint replacement surgery and premature mortality. The most simple and effective method of collecting important long-term data from patients in routine clinical care is through patient self-report questionnaires.

Pincus T, Ferraccioli G, Sokka T, Larsen A, Rau R, Kushner I, Wolfe F. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University School of Medicine, 203 Oxford House, Nashville, TN 37232-4500, USA. · Rheumatology (Oxford). · Pubmed #12468813 links to  free full text

Abstract: Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr to supplement data from randomized controlled clinical trials over 6-24 months.

Pincus T, Sokka T. · Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-4500, USA. · J Rheumatol. · Pubmed #11469488 No free full text.

Abstract: Predictors of longterm mortality in rheumatoid arthritis (RA) include patient questionnaire measures, grip strength, walk time, physician and patient assessment of global status, joint examination abnormalities, erythrocyte sedimentation rate (ESR), and morning stiffness. In the rheumatology literature, these measures have been analyzed primarily according to mean values in groups or regression analyses, which are valuable to recognize that mortality in RA is predicted by more severe disease, but do not provide the clinician with specific goals of therapy. Goals for therapeutic intervention are often expressed either as complete remission or as statistically significant differences versus a placebo, as in a 20% or even 50% response of a measure such as the American College of Rheumatology Core Data Set. Remission may be too stringent, while statistically significant efficacy of a drug compared to placebo may not necessarily indicate effectiveness to control longterm damage. An alternative approach might be to identify possible target values for therapeutic efficacy that markers of a poor prognosis be "near normal" rather than necessarily at normal or remission levels, as has been explored in management of hypertension and diabetes. However, it remains uncertain whether the goal of therapy should be a "near normal" or entirely normal values for a clinical marker. Better control of quantitative markers that predict early mortality could provide a valuable approach to improving outcomes in RA.

Sokka T, Pincus T. · Jyvaskyla Central Hospital, Department of Medicine, Finland. · J Rheumatol. · Pubmed #11469487 No free full text.

Abstract: Work disability is common in rheumatoid arthritis (RA), and accounts for a large fraction of its costs. People with RA who are work disabled have more joint involvement, radiographic damage, and/or laboratory abnormalities than people who are working. However, analysis of predictive and associative markers in 15 studies of work disability indicate that the demographic variables, such as age, occupation, level of education, and duration of disease, as well as functional status in activities of daily living (ADL) identified on a patient questionnaire, appear to identify work status more than physiological variables. Work disability results from complex interactions of a medical disease, demographic variables, social conditions, and government policies. Some patients with RA are work disabled before they see a rheumatologist. Improved work disability outcomes in RA will require attention to social, economic, and political issues, and wider physician and public education concerning RA, in addition to improved medical management of disease.

Pincus T, Sokka T. · Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, 203 Oxford House, Nashville, TN 37232, USA. · Best Pract Res Clin Rheumatol. · Pubmed #11358420 No free full text.

Abstract: The long-term natural history of rheumatoid arthritis includes early radiographic damage and progression, severe functional declines, work disability and increased mortality rates. Emerging evidence suggests that this natural history may be favourably affected by disease-modifying anti-rheumatic drugs (DMARDs), which slow the radiographic progression and functional decline. It is necessary to document both the efficacy of these drugs in randomized controlled clinical trials and their long-term effectiveness in clinical observational studies. Although a 20% improvement in inflammatory measures in the American College of Rheumatology Core Data Set (ACR20) distinguishes DMARDs from placebo in clinical trials, it is not clear that a control of inflammation at this level, or even at 50%, is sufficient to prevent long-term damage. There is limited financial support for long-term observational studies, which depend on data from the clinical experience of rheumatologists. Quantitative databases from clinical care, can be developed to document long-term outcomes in patients with early rheumatoid arthritis to include additional physical, radiographic, laboratory and patient questionnaire quantitative data. Patient self-report questionnaires appear to provide the least expensive and most effective measures toward this goal.

Sokka T, Möttönen T, Hannonen P. · Department of Medicine, Jyväskylä Central Hospital, Jyväskylä and. Turku University Central Hospital, Turku, Finland. · Rheumatology (Oxford). · Pubmed #10662871 links to  free full text

Abstract: OBJECTIVES: To investigate long-term functional outcomes of early rheumatoid arthritis (RA) patients treated actively with disease-modifying anti-rheumatic drugs (DMARDs) from diagnosis, according to the 'sawtooth' principle, and to compare the results to historical data. METHODS: The surviving 46 and 65 patients from two early RA cohorts were examined on average 13.0 (cohort 1) and 8.5 (cohort 2) yr, respectively, after onset of disease. Functional outcome was measured by the Health Assessment Questionnaire (HAQ) and compared with the HAQ scores of 57 RA patient cohorts found through a Medline computer search. RESULTS: The respective cross-sectional mean HAQ scores of cohorts 1 and 2 were 0.75 and 0. 55, and were more favourable than the mean HAQ scores of 1.27 (27 cohorts, disease duration >10 yr) and 1.13 (13 cohorts, disease duration 5-10 yr) of the comparator cohorts. The median time that our patients were treated with DMARDs out of the total follow-up period was 88%, while in the majority of comparator cohorts the use of DMARDs was less extensive or poorly described. CONCLUSIONS: The observation of better preserved function in patients with RA over 13 and 8.5 yr, compared to earlier reports which indicated more severe declines, is a hopeful sign for the rheumatology community.

Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Ave, Nashville, TN 37232, USA. · Arthritis Res Ther. · Pubmed #17169159 links to  free full text

Abstract: The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography. The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11 to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14], P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17]) than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification in patients with RA.

Häkkinen A, Sokka T, Kautiainen H, Kotaniemi A, Hannonen P. · Department of Physical Medicine and Rehabilitation, Jyväskylä Central Hospital, Keskussairaalantie 19, FIN-40620 Jyväskylä, Finland. · Ann Rheum Dis. · Pubmed #15249317 links to  free full text

Abstract: OBJECTIVE: To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength, bone mineral density (BMD), structural joint damage, and on disease activity in patients with early rheumatoid arthritis (RA). METHODS: Seventy patients were randomised either to perform home based strength training with loads of 50-70% of repetition maximum (EG) or range of motion exercises (CG). Both groups were encouraged to take part in aerobic activities 2-3 times a week. Maximal muscle strength of different muscle groups was measured by dynamometers, and BMD at the femoral neck and lumbar spine by dual x ray densitometry. Disease activity was assessed by the 28 joint disease activity score, and joint damage by x ray findings. RESULTS: 62 patients completed 2 years' training and 59 patients attended check up at 5 years. Mean (SD) maximum muscle strength indices increased from baseline to 2 years-in EG from 212 (78) kg by a mean (95% CI) of 68 (55 to 80) and in CG from 195 (72) kg by 35 (13 to 60) kg-and remained at that level for the next 3 years. Development of BMD in EG tended to be more favourable than that in CG. Muscle strength training was not detrimental to joint structures or disease activity. CONCLUSION: The patients' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years. Despite substantial training effects in muscle strength, BMD values remained relatively constant. Radiographic damage remained low even at 5 years.

Häkkinen A, Sokka T, Hannonen P. · Central Finland Health Care District, Jyväskylä, Finland. · Arthritis Rheum. · Pubmed #14872456 links to  free full text

Abstract: OBJECTIVE: To evaluate the impact of a 2-year home-based strength-training program on physical function in patients with early rheumatoid arthritis (RA) after a subsequent 3-year followup. METHODS: Seventy patients with early RA were randomized to perform either strength training (experimental group [EG]) or range-of-motion exercises (control group [CG]). Maximal strength values were recorded by dynamometers. The Modified Disease Activity Score (DAS28), pain, Health Assessment Questionnaire (HAQ), walking speed, and stair-climbing speed were also measured. RESULTS: The maximum strength of assessed muscle groups increased by 19-59% in the EG during the training period and remained at the reached level throughout the subsequent 3 years. Muscle strength improved in the CG by 1-31%, but less compared with the EG. During the 2-year training period, DAS28 decreased by 50% and 45% and pain by 67% and 39% in the EG and CG, respectively. The differences in muscle strength, DAS28, and HAQ were significantly in favor of the EG both at the 2-year and 5-year followup assessments. CONCLUSIONS: The improvements achieved during the 2-year strength-training period were sustained for 3 years in patients with early RA.

Häkkinen A, Sokka T, Kotaniemi A, Hannonen P. · Central Finland Health Care District, Jyväskylä, Finland. · Arthritis Rheum. · Pubmed #11263764 links to  free full text

Abstract: OBJECTIVE: To evaluate the impact of a 2-year program of strength training on muscle strength, bone mineral density (BMD), physical function, joint damage, and disease activity in patients with recent-onset (<2 years) rheumatoid arthritis (RA). METHODS: In this prospective trial, 70 RA patients were randomly assigned to perform either strength training (all major muscle groups of the lower and upper extremities and trunk, with loads of 50-70% of repetition maximum) or range of motion exercises (without resistance) twice a week; all were encouraged to engage in recreational activities 2-3 times a week. All patients completed training diaries (evaluated bi-monthly) and were examined at 6-month intervals. All were treated with medications to achieve disease remission. Maximum strength of the knee extensors, trunk flexors and extensors, and grip strength was measured with dynamometers. BMD was measured at the femoral neck and lumbar spine by dual x-ray densitometry. Disease activity was determined by the Disease Activity Score, the extent of joint damage by the Larsen score, and functional capacity by the Health Assessment Questionnaire (HAQ); walking speed was also measured. RESULTS: Sixty-two patients (31 per group) completed the study. Strength training compliance averaged 1.4-1.5 times/week. The maximum strength of all muscle groups examined increased significantly (19-59%) in the strength-training group, with statistically significant improvements in clinical disease activity parameters, HAQ scores, and walking speed. While muscle strength, disease activity parameters, and physical function also improved significantly in the control group, the changes were not as great as those in the strength-training group. BMD in the femoral neck and spine increased by a mean +/- SD of 0.51 +/- 1.64% and by 1.17 +/- 5.34%, respectively, in the strength-training group, but decreased by 0.70 +/- 2.25% and 0.91 +/- 4.07% in the controls. Femoral neck BMD in the 17 patients with high initial disease activity (and subsequent use of oral glucocorticoids) remained constantly at a statistically significantly lower level than that in the other 45 patients. CONCLUSION: Regular dynamic strength training combined with endurance-type physical activities improves muscle strength and physical function, but not BMD, in patients with early RA, without detrimental effects on disease activity.

Häkkinen A, Sokka T, Kotaniemi A, Kautiainen H, Jappinen I, Laitinen L, Hannonen P. · Department of Physical Therapy, Central Finland Health Care District, Jyväskylä. · J Rheumatol. · Pubmed #10381039 No free full text.

Abstract: OBJECTIVE: To assess the effects of 12 months' dynamic strength training on muscle strength and bone mineral density (BMD) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two subjects in the training group (EG) and 33 in the control group (CG) completed the study. EG carried out strength training 2 times a week with moderate loads of 50-70% of repetition maximum. They were also encouraged to do recreational physical activities. CG performed recreational physical activities and range of motion exercises. Maximal strength of the knee extensors, trunk extensors and flexors, and grip strength were recorded with dynamometers. BMD was measured using dual x-ray absorptiometry. Modified Disease Activity Score, erythrocyte sedimentation rate, and pain were used for the estimation of disease activity, and Stanford Health Assessment Questionnaire to measure functional disability. RESULTS: The 12 month resistance training in EG led to statistically significant mean increases of 22-35% in all muscle groups examined. CG patients were also able to increase their strength to some degree (3-24%), but at the end of the study strengths in CG were significantly lower than in EG. By the end of the study lumbar spine BMD had changed by +0.19% (4.24) in EG and by -1.14% (4.36) in CG. The corresponding changes of femoral BMD were +1.10% (3.71) and -0.03% (3.58). The changes in BMD were minor and statistically not significant in both groups. However, femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids (n = 15, 3 subjects from EG and 12 from CG) compared with changes in BMD among those not treated with systemic glucocorticoids (n = 50). CONCLUSION: Minimally supervised strength training resulted in significant improvements in muscle strength without detrimental effects on disease activity. The detected annual changes in central BMD were minor and statistically insignificant in both groups. Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment.

Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T, Shintani A, Pincus T, Stein CM. · Vanderbilt University, Nashville, Tennessee. · Arthritis Rheum. · Pubmed #19565493 No free full text.

Abstract: OBJECTIVE: Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA. METHODS: We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNFalpha]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFalpha, IL-6, and CRP). RESULTS: Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32-4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (rho = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17-0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42-1.73], P = 0.67). CONCLUSION: Concentrations of adipocytokines are increased in patients with RA and may modulate radiographic joint damage. Visfatin is associated with increased, and leptin with reduced, levels of radiographic joint damage.

Gregersen PK, Amos CI, Lee AT, Lu Y, Remmers EF, Kastner DL, Seldin MF, Criswell LA, Plenge RM, Holers VM, Mikuls TR, Sokka T, Moreland LW, Bridges SL, Xie G, Begovich AB, Siminovitch KA. · The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA. · Nat Genet. · Pubmed #19503088 No free full text.

Abstract: We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 x 10(-10)). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 x 10(-14)) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 x 10(-11)) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 x 10(-9)) and BLK (rs2736340; OR = 1.19; P = 5.69 x 10(-9)). c-Rel is an NF-kappaB family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.

Sokka T, Pincus T. · Jyväskylä Central Hospital, 40620 Jyväskylä, Finland. · J Rheumatol. · Pubmed #19411389 No free full text.

Abstract: OBJECTIVE: To analyze erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) tests in 2 databases of consecutive patients with rheumatoid arthritis (RA) over 25 years between 1980 and 2004, in Finland and the USA. METHODS: Databases of 1892 patients of 7 rheumatologists in Jyväskylä, Finland, and 478 of one author in Nashville, TN, USA, seen in usual care, were reviewed for the first recorded ESR and CRP, and all RF tests. RESULTS: Median ESR at presentation was 30 mm/h at both sites. Mean ESR was 36 mm/h in Jyväskylä and 35 mm/h in Nashville. ESR was < 28 mm/h in 45% and 47% of patients at the 2 sites, respectively. CRP was normal in 44% and 58%, and all RF tests were negative in 38% and 37%, respectively. Both ESR and CRP were normal in 33% and 42% of patients, and all 3 tests were normal in 15% and 14% of patients in whom they were assessed. All 3 tests were abnormal in only 28% in Jyväskylä and 23% in Nashville. CONCLUSION: A majority of patients with RA seen between 1980 and 2004 had abnormal ESR, CRP, or RF. However, more than 37% of patients had ESR < 28 mm/h, normal CRP, or all negative RF tests. Similarities of laboratory test data at 2 sites on different continents with different duration of disease suggest generalizability of the findings. Normal ESR, CRP, and RF are seen in a substantial proportion of patients with RA at this time.

Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW, Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T, Anonymous00057. · Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, and Medcare Oy, Hämeentie 1, 44100 Aänekoski, Finland. · Arthritis Res Ther. · Pubmed #19144159 links to  free full text

Abstract: ABSTRACT : INTRODUCTION : Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS : The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS : Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS : In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.

Häkkinen A, Arkela-Kautiainen M, Sokka T, Hannonen P, Kautiainen H. · Department of Physical Medicine and Rehabilitation, Jyväskylä Central Hospital, 40620 Jyväskylä, Finland. · J Rheumatol. · Pubmed #19040312 No free full text.

Abstract: OBJECTIVE: To assess disability and functioning of elderly patients with rheumatoid arthritis (RA) and population controls by linking the items included in the self-report Multidimensional Health Assessment Questionnaire (MDHAQ) with components of the WHO International Classification of Functioning, Disability and Health (ICF) instrument. METHODS: In total, 1439 patients with RA (mean age 66 yrs, men 29%) and 957 population controls (65 yrs, men 27%) completed a mailed questionnaire. Functioning was recorded by the Finnish version of MDHAQ. Data included comorbidity, subjective health, education level, employment, exercise habits, self-report joint pain/tenderness, and, for patients, the disease duration. RESULTS: Patients had lower levels of functioning compared to controls in all ICF domains, with the exception that male patients functioned comparably to male controls in the "general tasks and demands" domain. In patients, disease activity, education, exercise frequency, and comorbidities were expectedly associated with lower functioning in the body structure and function component, while male sex and subjectively perceived health were associated with more favorable functioning. In the activity and participation components, disease activity, exercise frequency, and comorbidities were associated with impaired functioning, while better health on self-report was associated with better functioning. CONCLUSION: There is an extra burden of disability in elderly patients with RA compared to the reference population. With a large patient and control population sample, our study shows that use of the self-report MDHAQ identifies all 3 main components of the ICF framework, thus covering a wide spectrum of functioning. Elderly patients with RA, in comparison to population controls, encounter more difficulties in daily activities and their social life.

Karonitsch T, Aletaha D, Boers M, Bombardieri S, Combe B, Dougados M, Emery P, Felson D, Gomez-Reino J, Keystone E, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Richards P, van Riel P, Siegel J, Smolen JS, Sokka T, van der Heijde D, van Vollenhoven R, Ward M, Wells G, Zink A, Landewe R. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791056 No free full text.

Abstract: OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Solus J, Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM. · Vanderbilt University Medical Center, Nashville, Tennessee. · Arthritis Rheum. · Pubmed #18759301 No free full text.

Abstract: OBJECTIVE: Increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation. METHODS: In 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated. RESULTS: NT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated. CONCLUSION: NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Sokka T, Pincus T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Rheumatology (Oxford). · Pubmed #18687711 links to  free full text

Abstract: OBJECTIVES: To analyse consecutive patients with RA in usual rheumatology care between 1980 and 2004 at two settings for the proportion of patients taking MTX, interval from patient presentation to MTX prescription and radiographic and functional status outcomes. METHODS: Longitudinal study of all patients seen in usual care between 1980 and 2004, 1982 consecutive patients in Jyväskylä, Finland and 738 consecutive patients in Nashville, TN, USA. Clinical status was assessed as Larsen radiographic scores in Jyväskylä and modified health assessment questionnaire (MHAQ) in Nashville. RESULTS: The probability of initiating MTX within 5 yrs after presentation increased from <5% in Jyväskylä before 1989 to >90% in 2000-04, and from 25% in Nashville in 1980-84 to >90% since 1995. The median interval from presentation to MTX initiation in Jyväskylä was 14 yrs in 1980-84 vs 8.6 in 1985-89, 4.5 in 1990-94, 1.8 in 1995-99 and <1 yr in 2000-05; in Nashville, median intervals were 8.6 yrs in 1980-84, 4.4 years in 1985-89, and <2 months in 1990-95, 1995-2000 and 2000-05. Patient outcomes were substantially improved in both settings: in Jyväskylä, mean 5-yr Larsen radiographic scores (0-100) were 15.7 in 1980-84 vs 4.0 in 1995-99; in Nashville, mean MHAQ scores (0-3) for physical function were 1.13 in 1980-84 vs 0.57 in 2000-04. CONCLUSION: Early MTX in usual clinical care of RA increased from <5% in 1980 to >90% in 2004. Over this period, substantially improved outcomes were seen, most of which antedated biological agents.

Hakkinen A, Makinen H, Ylinen J, Hannonen P, Sokka T, Neva M, Kautiainen H, Kauppi M. · Department of Physical Medicine and Rehabilitation, Jyväskylä Central Hospital, Jyväskylä, Finland. · Scand J Rheumatol. · Pubmed #18609259 No free full text.

Abstract: OBJECTIVE: To study the effect of isometric neck strength exercises on upper cervical stability in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with a mean (SD) age of 58 (9) years and duration of RA of 27 (10) years volunteered for the study. Lateral radiographs of the cervical spine were taken to measure the current atlantoaxial distance (AAD) in flexion and extension. Maximal isometric neck flexion and extension strength values were measured by a dynamometer. Thereafter, AADs were measured from radiographs taken at 80-90% resistance of maximal strength. RESULTS: According to the full flexion radiographs at baseline, the patients were classified into three groups: eight patients without anterior atlantoaxial subluxation (aAAS) [AAD = 2.1 (2-3) mm], seven with unstable aAAS [AAD = 6.6 (5-8) mm], and five with stable aAAS [AAD = 5.5 (5-7) mm]. During resisted flexion the AAD decreased by 5 (3-7) mm (p<0.001) in the unstable aAAS group, while in the other two groups the changes were minor. During resisted extension the AAD increased by 3 (2-6) mm (p<0.001) in the cases with unstable aAAS only. CONCLUSION: Isometric exercising towards flexion decreases the AAD in cases with unstable aAAS. Submaximal loading of the neck extensors by pushing the back of the head against the resistance even in the neutral position of the cervical spine leads to a decrease in the width of the cervical spine canal and is not recommended in unstable aAAS.