Rheumatoid Arthritis: Mäkinen H

Mäkinen H, Hannonen P. · No affiliation provided · J Rheumatol. · Pubmed #19208530 No free full text.

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Sokka T, Mäkinen H. · No affiliation provided · J Rheumatol. · Pubmed #16821259 links to  free full text

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Sokka T, Mäkinen H. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Best Pract Res Clin Rheumatol. · Pubmed #19233049 No free full text.

Abstract: Modern therapy of rheumatoid arthritis (RA) is based on recognition of the severity of the natural history of disease, with early and aggressive treatment strategies. Methotrexate is the anchor drug, with addition of other disease-modifying anti-rheumatic drugs (DMARDs) in combinations, and biological targeted therapies. The approach emphasizes 'tight control', aiming for remission and low disease activity according to quantitative monitoring. In this chapter, we review selected randomized controlled studies for data concerning early versus delayed therapies. We present a historical perspective for the treatment of early RA using early RA cohorts from Finland as an example. Finally, we discuss principles of contemporary treatment of early RA in 2008.

Mäkinen H, Hannonen P, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #17083758 No free full text.

Abstract: Various definitions of remission in rheumatoid arthritis (RA) have been proposed. The ACR (American College of Rheumatology--formerly ARA, American Rheumatism Association) remission criteria are strict and include nonspecific symptoms such as fatigue. More recently remission according to the Disease Activity Index (DAS) and DAS28 has been described. However, patients who meet the DAS28 remission cut point of < 2.6 may nonetheless have tender and/or swollen joints. The ACR remission criteria are more rigorous than the requirement of DAS28 <2.6. Newer tools for evaluation of RA activity include the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and cut points for remission according to these new indices have been defined. However, all available remission criteria may ignore important aspects of RA, including physical function and radiographic damage.

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.

Mäkinen H, Kautiainen H, Hannonen P, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · J Rheumatol. · Pubmed #18484699 No free full text.

Abstract: OBJECTIVE: To develop a continuous composite index of disease activity for rheumatoid arthritis (RA) based on the 7 American College of Rheumatology (ACR) core data set of disease activity measures: Mean Overall Index for Rheumatoid Arthritis (MOI-RA). METHODS: The MOI-RA is the mean of standardized values of tender and swollen joint counts (28, 42, or 66/68 joint counts), physical function (Health Assessment Questionnaire 0-3), patient's and physician's assessments of global health and patient's assessment of pain (visual analog scale 0-100 mm) and erythrocyte sedimentation rate (1-100). All the 7 components were standardized (0-100), and the mean of standardized values was calculated. The range of MOI-RA is 0-100; higher values indicate poorer outcomes. The validity and measurement properties of MOI-RA were analyzed in 169 patients in the Finnish RA Combination therapy trial. RESULTS: The mean MOI-RA28 decreased from 38.5 to 13.3 [standardized response mean (SRM) = 1.8, effect size (ES) = 1.9] from baseline to 6 months, compared to Disease Activity Score (DAS) 28, which decreased from 5.55 to 2.77 (SRM = 2.0, ES = 2.8). Correlation between MOI-RA28 and DAS28 was 0.90. When compared to the ACR response categories (20/50/ACR remission), changes in MOI-RA versions (using 28/42/66 joints) were similar. The reproducibility of MOI-RA with different joint counts was 0.97. A simulation in which 15% of the component values of MOI-RA were randomly omitted indicated an intraclass correlation coefficient of 0.98 between incomplete and complete data. CONCLUSION: MOI-RA is a simple and feasible index based on the ACR core data set of disease activity measures for assessment of disease activity and treatment response in RA trials and clinical settings.

Mäkinen H, Kautiainen H, Hannonen P, Möttönen T, Korpela M, Leirisalo-Repo M, Luukkainen R, Puolakka K, Karjalainen A, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · J Rheumatol. · Pubmed #17611990 No free full text.

Abstract: OBJECTIVE: To examine the influence of components of the Disease Activity Score 28 (DAS28) [tender joint count (TJC), swollen joint count (SJC), patient's general health (GH), and erythrocyte sedimentation rate (ESR)] on the total DAS28 score, and overlapping of the 4 individual components in rheumatoid arthritis (RA) patients with low, moderate, or high disease activity. METHODS: The effect of each component was studied in the FIN-RACo trial patients at 6 months and in a "theoretical model," where each component of the DAS28 ranged as follows: TJC and SJC from 0 to 28, GH from 0 to 100, and ESR from 1 to 100, while the other 3 components were 0 (ESR1). Overlapping of the components was studied in the FIN-RACo trial patients at 6 months with low (DAS28 < or = 3.2), moderate (DAS28 > 3.2 and < or = 5.1), and high (DAS28 > 5.1) disease activity. The higher limit for overlapping was defined as the highest SJC in the low disease activity group, and the lower limit as the lowest SJC in the high disease activity group; the percentage of patients who fall between these limits represent overlapping in SJC. Overlapping was calculated similarly concerning TJC, ESR, and GH. RESULTS: ESR had the greatest effect on DAS28, followed by TJC, GH, and SJC, while in the "theoretical model" TJC had the greatest effect on the DAS28, followed by ESR, SJC, and GH. At 6 months, overlapping was present in 54%, 45%, 49%, and 31% of patients in SJC, TJC, GH, and ESR, respectively. CONCLUSION: In real-life patients, ESR had the greatest effect of the 4 components of DAS28 on the total DAS28 score. The values of the individual components of DAS28 overlap considerably among the 3 disease activity groups.

Sokka T, Kautiainen H, Toloza S, Mäkinen H, Verstappen SM, Lund Hetland M, Naranjo A, Baecklund E, Herborn G, Rau R, Cazzato M, Gossec L, Skakic V, Gogus F, Sierakowski S, Bresnihan B, Taylor P, McClinton C, Pincus T, Anonymous00159. · Arkisto/Tutkijat, Jyvaskyla Central Hospital, 40620 Jyvaskyla, Finland. · Ann Rheum Dis. · Pubmed #17412740 No free full text.

Abstract: OBJECTIVE: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. METHODS: The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. RESULTS: Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 <or=3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. CONCLUSIONS: This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.

Sokka T, Mäkinen H, Hannonen P, Pincus T. · Jyvaskyla Central Hospital, 40620 Jyvaskyla, Finland. · Rheumatology (Oxford). · Pubmed #17405761 links to  free full text

Abstract: OBJECTIVE: To analyse the proportion of individuals in the general population over age 50 who do not meet American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA) remission, and OMERACT criteria for minimal disease activity (MDA), and to compare results to RA patients. METHODS: A self-report questionnaire was completed by 1400 community control subjects and 1705 RA patients, including the Health Assessment Questionnaire (HAQ), gradual rating scales for pain, fatigue and global health, duration of morning stiffness and painful joints. The prevalence of 4/6 ACR remission criteria and 4/7 OMERACT criteria for MDA was analysed in community control subjects and patients with RA over age 50. RESULTS: For ACR criteria, 76% of control subjects reported painful joints, 37% morning stiffness, 62% pain and 66% fatigue, vs 94, 65, 84 and 84% of patients with RA. MDA criteria were not met by 64% of control subjects for painful joints, 38% for pain, 45% for global health and 18% for HAQ, vs 89, 60, 69 and 52% of RA patients. The four ACR remission criteria were met by only 15% of control subjects over age 50 and 3% of RA patients, and MDA criteria by 28% of controls and 7% of patients. CONCLUSIONS: The majority of community population over age 50 did not meet criteria for remission or MDA in RA. Although a self-report format may differ from results involving an assessor, the current criteria may not be accurate to identify remission or MDA in people with RA who are older than age 50.

Mäkinen H, Kautiainen H, Hannonen P, Möttönen T, Leirisalo-Repo M, Laasonen L, Korpela M, Blåfield H, Hakola M, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · J Rheumatol. · Pubmed #17183623 No free full text.

Abstract: OBJECTIVE: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). METHODS: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months. CONCLUSION: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.

Sokka T, Mäkinen H, Puolakka K, Möttönen T, Hannonen P. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #17083766 No free full text.

Abstract: The Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial is the first rheumatoid arthritis (RA) clinical trial in which remission served as the primary outcome measure. This chapter reviews the philosophical background, study design, and results of the FIN-RACo trial. The study showed that a third of patients with active early RA may achieve remission with a combination of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), and prednisolone.

Neva MH, Häkkinen A, Mäkinen H, Hannonen P, Kauppi M, Sokka T. · Department of Orthopaedic and Trauma Surgery, Tampere University Hospital, PL 2000, 33521 Tampere, Finland. · Ann Rheum Dis. · Pubmed #16269427 links to  free full text

Abstract: OBJECTIVE: To study the prevalence of cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery, and symptoms that might be associated with the disorders. METHODS: 194 patients with rheumatoid arthritis were referred for orthopaedic surgery at Jyväskylä Central Hospital, 154 (79%) of whom volunteered for the present study including clinical examination, laboratory tests, radiographs of the cervical spine, hands, and feet, and self report questionnaires. Definition of anterior atlantoaxial subluxation (aAAS) was >3 mm and of subaxial subluxation (SAS)>or=3 mm. Atlantoaxial impaction (AAI) was analysed following to the Sakaguchi-Kauppi method. RESULTS: 67 patients (44%) had cervical spine subluxation or previous surgical fusion. The prevalence of aAAS, AAI, SAS, or previous fusion was 27 (18%), 24 (16%), 29 (19%), and 8 (5%), respectively; 69% of patients with cervical spine subluxations (those with fusions excluded) reported neck pain, compared with 65% of patients without subluxations (p=0.71). The prevalence of occipital, temporal, retro-orbital, and radicular pain in upper extremities was similar in patients with or without cervical spine subluxations (54% v 43%; 17% v 31%; 25% v 24%; 47% v 48%, respectively). However, patients with subluxations were older, had longer disease duration, more active disease, poorer function according to the Health Assessment Questionnaire, and had more often erosive disease. CONCLUSIONS: Asymptomatic cervical spine subluxation is common in patients with rheumatoid arthritis waiting for orthopaedic surgery. Regardless of symptoms, the possibility of cervical spine subluxation in patients with severe rheumatoid arthritis should be considered in preoperative evaluation.

Häkkinen A, Neva MH, Kauppi M, Hannonen P, Ylinen J, Mäkinen H, Jäppinen I, Sokka T. · Department of Physical Medicine and Rehabilitation, Jyväskylä Central Hospital, Jyväskylä, Finland. · Arch Phys Med Rehabil. · Pubmed #16084814 No free full text.

Abstract: OBJECTIVE: To compare neck muscle strength and mobility of the cervical spine in rheumatoid arthritis (RA) patients with and without atlantoaxial (AA) disorders (anterior atlantoaxial subluxation [AAS], AA impaction). DESIGN: Clinical cross-sectional study. SETTING: Outpatient rheumatology and rehabilitation clinics in a Finnish hospital. PARTICIPANTS: Patients with RA (N=124; mean age +/- standard deviation, 62+/-12y [corrected]) on a waiting list for orthopedic surgery. Thirty (24%) patients presented with AA disorders (16 with anterior AAS, 8 with AA impaction, 6 with a combination of anterior AAS and AA impaction). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neck function was measured by isometric neck strength and mobility tests, neck pain by a visual analog scale, erosion of the hands and feet by radiography, and the patients' function by the Health Assessment Questionnaire (HAQ). RESULTS: Maximal neck muscle strength against flexion, extension, and rotation was lower in patients with AA disorders compared with the other patients in both women (P=.012) and men (P=.017). Mobility was lowest in the AA impaction group in all measured directions (P<.001). Peripheral erosive disease was more frequent in the group with AA disorders. They also had longer disease duration and were more disabled (HAQ) than the other patients. CONCLUSIONS: Neck muscle strength is significantly decreased in patients with AA disorders. Mobility of the cervical spine is most limited in patients with AA impaction, but can be normal in cases with solitary anterior AAS.

Mäkinen H, Kautiainen H, Hannonen P, Sokka T. · Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland. · Ann Rheum Dis. · Pubmed #15941836 links to  free full text

Abstract: OBJECTIVES: To study which cut off point of DAS28 corresponds to fulfilment of the American Rheumatism Association (ARA) preliminary remission criteria, and clinical remission criteria in patients with rheumatoid arthritis (RA). METHODS: All adult patients diagnosed with RA at Jyväskylä Central Hospital 1997-98 were assessed for remission at 5 years. Remission was defined as (a) ARA remission; (b) clinical remission (defined as no tender or swollen joints and normal erythrocyte sedimentation rate). DAS28 was used to measure disease activity. A receiver operating characteristics curve analysis was performed to calculate a cut off point of DAS28 that best corresponds to the ARA remission criteria and the clinical remission criteria. RESULTS: 161 patients (mean age 57 years, 107 (66%) female, 98 (61%) with positive rheumatoid factor, and 51 (32%) with erosions) were studied. At 5 years, 19 (12%) patients met the ARA remission criteria, and 55 (34%) met the clinical remission criteria. The cut off value of DAS28 was 2.32 for the ARA remission criteria, and 2.68 for the clinical remission criteria. In patients with DAS28 <2.32, 11/57 (19%) had tender joints, 6/57 (11%) had swollen joints, and 4/57 (7%) had both tender and swollen joints (66 joint count). CONCLUSION: In this study the DAS28 cut off point for the ARA remission was lower than in previous studies. The cut off point for DAS28 remission remains controversial. A substantial proportion of patients below the DAS28 cut off point for remission have tender or swollen joints, or both. DAS28 may not be an appropriate tool for assessment of remission in RA.

Häkkinen A, Kautiainen H, Hannonen P, Ylinen J, Mäkinen H, Sokka T. · Department of Physical Medicine and Rehabilitation, Jyväskylä Central Hospital, Finland. · Ann Rheum Dis. · Pubmed #15901635 links to  free full text

Abstract: OBJECTIVE: To study the extent to which muscle strength and performance, pain, and disease activity are associated with the total Health Assessment Questionnaire (HAQ) disability index and its subdimensions in male and female patients with rheumatoid arthritis. METHODS: HAQ for functional capacity was completed by 135 patients with rheumatoid arthritis referred for orthopaedic surgery (74% women; mean (SD) age 62 (10) years; disease duration 19 (13) years, 70% positive for rheumatoid factor). Knee extension, trunk extension and flexion, grip strength, walking speed, and sit-to-stand test were measured to mirror physical function. Radiographs of hands and feet, pain, and the modified 28 joint disease activity score (DAS28) were also assessed. RESULTS: Mean total HAQ was 1.08 (0.68) in women and 0.67 (0.70) in men (p = 0.0031). Women had greater disability than men in five of the eight subdimensions of the HAQ. Grip strength was 48%, knee extension strength 46%, trunk extension strength 54%, and trunk flexion strength 43% lower in women than in men. Knee extension strength was inversely correlated with walking time (r = -0.63 (95% confidence interval, -0.73 to -0.51)) and with sit-to-stand test (r = -0.47 (-0.60 to -0.31)). In an ordered logistic regression analysis in female rheumatoid patients, DAS28, pain, knee extension strength, and grip strength were associated with the total HAQ disability index. CONCLUSIONS: Women reported greater disability than men both in the total HAQ and in the majority of its eight subdimensions. In addition to disease activity and pain, muscle strength has a major impact on disability especially in female rheumatoid patients.

Mäkinen H, Kautiainen H, Hannonen P, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · J Rheumatol. · Pubmed #15868611 No free full text.

Abstract: OBJECTIVE: To study the frequency of remission using 3 sets of criteria in patients with rheumatoid arthritis (RA) at 5 years after the diagnosis. METHODS: All adult patients with recent onset inflammatory arthritis who did not meet criteria or show clinical signs of other specific arthritides were included in the RA1997 inception cohort at Jyväskylä Central Hospital, Finland, and were assessed for remission at 5-year control examination. Remission was defined as (1) American College of Rheumatology (ACR) remission (fatigue excluded), (2) clinical remission with no tender and no swollen joints and normal erythrocyte sedimentation rate, and (3) radiographic remission with no worsening of erosions and no new erosions from baseline to 5 years. RESULTS: The study included 127 patients with early RA (mean age 56 yrs, 61% female, 54% with positive rheumatoid factor, and 25% with erosions). At 5 years, 111 patients were examined, 17% (95% CI 11%-25%) of whom met ACR remission criteria, 37% (95% CI 28%-47%) met clinical remission criteria, and 55% (95% CI 49%-68%) met radiographic remission criteria. Only 13 (12%) patients met all 3 sets of remission criteria. The rate of remission was statistically significantly different (p < 0.001) using the 3 sets. CONCLUSION: The rate of remission in RA depends on the criteria used. No gold standard exists for defining remission in RA. A set of criteria including no sign of inflammatory activity and no radiographic progression might be a basis for development of clinically relevant remission criteria for RA.

Mäkinen H, Hannonen P, Sokka T. · No affiliation provided · Ann Rheum Dis. · Pubmed #18556449 No free full text.

This publication has no abstract.