Rheumatoid Arthritis: Hannonen P

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

This publication has no abstract.

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, Hannonen P, Möttönen T. · Department of Rheumatology, Jyväskylä Central Hospital, Jyväskylä, Finland. · Rheum Dis Clin North Am. · Pubmed #16287594 No free full text.

Abstract: This article reviews the use of conventional disease-modifying antirheumatic drugs (DMARDs) in the treatment of early rheumatoid arthritis (RA). The Finnish early RA cohorts are used as examples of how early and active treatment strategies have improved over time with increasing variety of available DMARDs. Therapy goals of early RA include remission to prevent severe long-term outcomes of RA. Remission can be achieved in a third of patients with early RA using a combination of conventional DMARDs, including methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone. Of patients with early RA, 20% to 30% do not improve enough with conventional treatments and should be identified at early phases to consider institution of biologic agents.

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.

Kuuliala A, Leirisalo-Repo M, Möttönen T, Hannonen P, Nissilä M, Kautiainen H, Korpela M, Julkunen H, Hakola M, Repo H, Anonymous00299. · Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland. · Clin Exp Rheumatol. · Pubmed #15895898 No free full text.

Abstract: OBJECTIVE: To study the value of baseline serum levels of circulating soluble interleukin-2 receptor (sIL-2R) and soluble E-selectin as predictors of early remission in patients with recent-onset rheumatoid arthritis (RA) receiving a single disease-modifying anti-rheumatic drug (DMARD) (SINGLE) or therapy with a combination of DMARDs (COMBI). METHODS: Baseline (n = 157) serum samples originate from the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, in which 195 patients with early and clinically active RA were randomly assigned to receive either SINGLE (initially sulfasalazine) with or without prednisolone, or COMBI therapy (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone). Of the samples, 76 were from SINGLE patients and 81 from COMBI patients. sIL-2R was measured by automated immunoassay analyzer and sE-selectin by enzyme-linked immunosorbent assay. RESULTS: At six months, 7 (9% [95% CI: 4 to 18]) SINGLE and 19 (23% [95% CI: 15 to 34]) COMBI patients were in remission. In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. The area under receiver operating characteristic curve for sIL-2R level was 0.86 (95% CI: 0.62 to 0.95) in SINGLE and 0.57 (95% CI: 0.42 to 0.71) in COMBI (p = 0.006). In SINGLE, the optimal cut offpoint was 442 U/ml, lower levels predicting remission with sensitivity of 83% (95% CI: 73% to 91%) and specificity of 86% (95% CI: 42% to 100%). Likelihood ratio for positive test was 5.9 (95% CI: 1.6 to 32.8). In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. CONCLUSION: Low baseline serum sIL-2R level predicts early remission of patients with active early RA treated with a single DMARD.

Puolakka K, Kautiainen H, Möttönen T, Hannonen P, Korpela M, Hakala M, Järvinen P, Ahonen J, Forsberg S, Leirisalo-Repo M, Anonymous00147. · Department of Medicine, Lappeenranta Central Hospital, Valto Käkelän katu 1, Lappeenranta FIN-53130, Finland. · Arthritis Rheum. · Pubmed #15641055 links to  free full text

Abstract: OBJECTIVE: To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomized to receive either a combination of disease-modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5-year followup, the cumulative number of days of sick leave and RA-related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline. RESULTS: Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient-year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0-3), 4 (IQR 0-131), 16 (IQR 0-170), and 352 (16-365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5-year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%). CONCLUSION: Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.

Puolakka K, Kautiainen H, Möttönen T, Hannonen P, Hakala M, Korpela M, Ilva K, Yli-Kerttula U, Piirainen H, Leirisalo-Repo M, Anonymous00040. · Department of Medicine, Lappeenranta Central Hospital, Valto Käkelän katu 1, FIN-53130 Lappeenranta, Finland. · Ann Rheum Dis. · Pubmed #15608311 links to  free full text

Abstract: OBJECTIVE: To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early, active RA. PATIENTS AND METHODS: In the FIN-RACo trial, 195 patients with recent onset RA were randomised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years. At baseline, 162 patients were working or available for work. After 5 years' follow up, data on sick leave and retirement were obtained from social insurance registers or case records. The cumulative duration of sick leaves and RA related disability pensions was counted for each patient. To analyse predictors of productivity loss, the patients were divided into four groups according to duration of work disability per patient year. RESULTS: Patient's and physician's global assessment of RA severity > or =50 and HAQ score > or =1.0 were risk factors for extension of productivity loss (OR (95% (CI) 1.77 (1.00 to 3.16), 1.85 (1.03 to 3.32), and 1.78 (1.01 to 3.14), respectively). Additional risk factors were low education level (2.40 (1.18 to 4.88)) and older age (1.03 (1.00 to 1.06)); combination treatment was a protective factor (0.59 (0.35 to 0.99)). CONCLUSION: At baseline, the risk of future productivity loss is best predicted by education level, age, global assessments of RA severity, and HAQ score.

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.

Korpela M, Laasonen L, Hannonen P, Kautiainen H, Leirisalo-Repo M, Hakala M, Paimela L, Blåfield H, Puolakka K, Möttönen T, Anonymous00438. · Tampere University Hospital, Tampere, Finland. · Arthritis Rheum. · Pubmed #15248204 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score. RESULTS: A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively. CONCLUSION: Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.

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.

Puolakka K, Kautiainen H, Möttönen T, Hannonen P, Korpela M, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blåfield H, Hakala M, Leirisalo-Repo M. · Lappeenranta Central Hospital, Lappeenranta, Finland. · Arthritis Rheum. · Pubmed #14730599 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. RESULTS: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods </=300 days): median 11.7 days (IQR 0-44) per patient-observation year in those treated with combination therapy and 30.0 days (IQR 6-68) in those treated with single therapy (P = 0.002). No statistically significant difference was seen in RA-related disability pensions. CONCLUSION: Aggressive initial treatment of RA with a combination of DMARDs improves 5-year outcome in terms of lost productivity in patients with RA of recent onset.

Häkkinen A, Hannonen P, Nyman K, Lyyski T, Häkkinen K. · Department of Physical Medicine and Rehabilitation, Central Finland Health Care District, Central Hospital, Keskussairaalantie 19, Jyväskylä, Finland 40620. · Arthritis Rheum. · Pubmed #14673965 links to  free full text

Abstract: OBJECTIVE: To investigate the effects of a 21-week concurrent strength and endurance training protocol on physical fitness profile in women with early or longstanding rheumatoid arthritis (RA) compared with healthy subjects. METHODS: Twenty-three female patients with RA volunteered for the study. Twelve had early RA and eleven had longstanding RA. Twelve healthy women served as controls. Maximal strength of different muscle groups was measured by dynamometers, walking speed with light cells, and vertical squat jump on the force platform to mirror explosive force. Maximal oxygen uptake was measured by gas analyzer. Six training sessions (3 strength training and 3 endurance training) were carried out in a 2-week period for 21 weeks. RESULTS: The training led to large gains in maximal strength both in women with RA and in healthy women (P < 0.043-0.001). The strength gains were accompanied by increases in walking speed (P < 0.034-0.001) and vertical squat jump (P < 0.034-0.001). Significant improvements also occurred in maximal aerobic capacity in all groups (P < 0.023-0.014). CONCLUSIONS: Both early and longstanding RA patients with stable disease can safely improve all characteristics of their physical fitness profile using a progressive concurrent strength and endurance training protocol.

Kvien TK, Zeidler HK, Hannonen P, Wollheim FA, Førre O, Hafström I, Kaltwasser JP, Leirisalo-Repo M, Manger B, Laasonen L, Prestele H, Kurki P. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #12006323 links to  free full text

Abstract: OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Möttönen T, Hannonen P, Korpela M, Nissilä M, Kautiainen H, Ilonen J, Laasonen L, Kaipiainen-Seppänen O, Franzen P, Helve T, Koski J, Gripenberg-Gahmberg M, Myllykangas-Luosujärvi R, Leirisalo-Repo M, Anonymous00036. · Department of Medicine, Turku University Central Hospital, Turku, Finland. · Arthritis Rheum. · Pubmed #11953964 No free full text.

Abstract: OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in 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.

Neva MH, Kauppi MJ, Kautiainen H, Luukkainen R, Hannonen P, Leirisalo-Repo M, Nissilä M, Möttönen T, Anonymous00034. · Jyväskylä Central Hospital, Finland. · Arthritis Rheum. · Pubmed #11083260 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy of combination therapy with disease-modifying antirheumatic drugs (DMARDs) versus single therapy with DMARDs in the prevention of early cervical spine changes in patients with rheumatoid arthritis (RA). METHODS: One hundred ninety-five patients with recent-onset RA (mean disease duration 8 months) were randomly assigned to receive a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single DMARD with or without prednisolone. After 2 years of followup, cervical spine radiographs were taken of 176 of these patients (85 in the combination-therapy group and 91 in the single-therapy group). These radiographs were evaluated, and the findings were correlated with the therapy strategies as well as with peripheral joint destruction and clinical and laboratory variables describing the disease activity. RESULTS: Anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI; i.e., vertical subluxation), and subaxial subluxation (SAS) were found in only 6 (3.4%), 2 (1.1%), and 5 (2.8%) of the patients, respectively. Interestingly, none of the patients in the combination-therapy group had aAAS or AAI. The incidences of aAAS and AAI in the single-therapy group were 6.6% and 2.2%, respectively. SAS was present in 2 patients (2.2%) in the single-therapy group and in 3 patients (3.5%) in the combination-therapy group. The difference in the incidence of aAAS between the treatment groups was statistically significant (P = 0.029). None of the patients with cervical spine changes achieved remission of RA during the study. CONCLUSION: In the present study, the incidence of cervical spine subluxations in patients treated with single-drug therapy was in accord with findings of previous studies. However, none of the patients in the combination-therapy group had aAAS or AAI. These findings suggest that early, aggressive combination-DMARD therapy with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone can prevent or retard the development of rheumatoid atlantoaxial disorders.

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.

Möttönen T, Hannonen P, Leirisalo-Repo M, Nissilä M, Kautiainen H, Korpela M, Laasonen L, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blåfield H, Hakala M, Ilva K, Yli-Kerttula U, Puolakka K, Järvinen P, Hakola M, Piirainen H, Ahonen J, Pälvimäki I, Forsberg S, Koota K, Friman C. · Division of Rheumatology, Turku University Central Hospital, Finland. · Lancet. · Pubmed #10334255 No free full text.

Abstract: BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

Anderson IF, Helve T, Hannonen P, Leirisalo-Repo M, Gilboe IM, Nissilä M, Keystone EC, Kraag GR, Bjørneboe O, Chalmers A, Dovland H, Mueller E, Richard F, Whatmough I, Schmidt AG, Kovarik JM. · Pretoria Rheumatology Institute, Pretoria Academic Hospital, South Africa. · J Rheumatol. · Pubmed #10090162 No free full text.

Abstract: OBJECTIVE: To assess whether patients with rheumatoid arthritis (RA) may be converted, on a milligram-to-milligram basis, from conventional cyclosporin A (CyA, Sandimmun) to the microemulsion formulation (Neoral) with maintenance of longterm safety, and to compare cyclosporin A (CyA) pharmacokinetics between formulations. METHODS: In this double blind, multicenter, parallel group study, 51 patients receiving stable conventional CyA maintenance treatment were randomized to continue conventional CyA (n = 27) or to convert to CyA microemulsion (n = 24) and were monitored for 52 weeks. Trough blood CyA levels were measured before and at intervals after conversion. CyA steady-state area under the curve was assessed one week before and 2 and 6 weeks after randomization in 15 patients in each treatment arm. CyA trough levels and pharmacokinetic results remained unknown to investigators throughout the study. CyA doses were titrated as necessary on the basis of clinical evaluation and disease activity assessments. RESULTS: Initial mean daily doses were 3.5 mg/kg/day (conventional CyA) and 3.3 mg/kg/day (CyA microemulsion) and did not change significantly during the study. The mean bioavailability of CyA from the microemulsion formulation was 23% higher than from conventional CyA. Replicate assessments indicated a more reproducible pharmacokinetic profile with CyA microemulsion. The overall incidence and nature of adverse events and changes in vital signs and laboratory variables were similar in both groups. No clinically relevant differences in efficacy were found between treatments. No loss of efficacy and no tolerability problems occurred after conversion from conventional to microemulsion CyA. CONCLUSION: Existing CyA dosing guidelines, formulated for conventional CyA, are suitable for longterm CyA microemulsion therapy of patients with RA. These results indicate the pharmacokinetic advantages of the microemulsion formulation.

Puolakka K, Kautiainen H, Möttönen T, Hannonen P, Korpela M, Hakala M, Viikari-Juntura E, Solovieva S, Arkela-Kautiainen M, Leirisalo-Repo M. · Department of Medicine, Lappeenranta Central Hospital, Lappeenranta, Finland. · Clin Exp Rheumatol. · Pubmed #19604434 No free full text.

Abstract: OBJECTIVE:To explore the combination of data on functioning and work load for early identification of patients at risk for diminished work productivity in rheumatoid arthritis (RA).PATIENTS AND METHODS:In the FIN-RACo trial, 162 patients with recent onset RA and available for the workforce were treated with either a combination of disease-modifying antirheumatic drugs (DMARDs) or a single DMARD for 2 years. Otherwise, they received routine care and were followed up for 5 years. Data on their individual income and lost work days came from official registers. Loss of productivity was computed by the human capital approach. Self-reported data on physical work demand (Finnish Institute for Occupational Health Questionnaire) at baseline and on functioning (HAQ) at 6 months were linked according to the International Classification of Functioning, Disability and Health. RESULTS:Data on 112 patients were analyzable at 6 months; 35 (31%) of them had diminished capacity in functions required at paid work. Any mismatch between perceived abilities and requirements predicted future (7 through 60 months) loss of productivity - on average Euro 14,040 (95% confidence interval (CI): 9,143-20,511) per year in patients with the mismatch compared to Euro 3,043 (1,623-5,534) in those without any mismatch - and was associated with RA-related permanent work disability (hazard ratio: 11.6; 95%CI: 4.0-33.4).CONCLUSION:Linking together self-reported data about functioning and work load helps in early identification of the RA patients at risk for loss of working days.

Rantalaiho V, Korpela M, Hannonen P, Kautiainen H, Järvenpää S, Leirisalo-Repo M, Hakala M, Puolakka K, Julkunen H, Luosujärvi R, Möttönen T, Anonymous00066. · Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland. · Arthritis Rheum. · Pubmed #19404945 No free full text.

Abstract: OBJECTIVE: To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission. RESULTS: At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. CONCLUSION: Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.

Uutela T, Hannonen P, Kautiainen H, Hakala M, Paananen ML, Häkkinen A. · Department of Medicine, Central Hospital of Lapland, Rovaniemi, Finland. · Clin Exp Rheumatol. · Pubmed #19327237 No free full text.

Abstract: OBJECTIVE: To examine treatment induced changes in health-related quality of life (HR-QoL) in patients with early rheumatoid arthritis (RA). METHODS: Changes in HR-QoL were assessed by the Nottingham Health Profile (NHP) instrument in 62 consecutive working age patients with recent onset RA with duration of symptoms of less than two years and naive with regard to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. Treatment-response was assessed by the criteria of the European League against Rheumatism (EULAR; 28-joint score; DAS28) at 6 months. RESULTS: NHP mean scores for pain (p=0.029) and emotional reaction (p=0.035) at baseline were related to EULAR response at 6 months, i.e. non-responders had the poorest baseline HR-QoL scores. When the patients were grouped according to EULAR response at 6 months there was a statistically significant mean linear change to better HR-QoL in NHP energy (p=0.0023), pain (p<0.001) and mobility (p=0.0085) from baseline to 6 months from the lowest to highest treatment-response level. CONCLUSION: Our results show that good treatment-response as measured by the EULAR response criteria translates into improved HR-QoL dimensions for energy, pain and mobility.

Puolakka K, Kautiainen H, Mottonen T, Hannonen P, Korpela M, Hakala M, Luukkainen R, Vuori K, Blåfield H, Leirisalo-Repo M. · Lappeenranta Central Hospital, Lappeenranta, Finland. · Scand J Rheumatol. · Pubmed #19274516 No free full text.

Abstract: OBJECTIVE: To evaluate the utility of the Stanford Health Assessment Questionnaire (HAQ) in the estimation of loss of productivity due to early rheumatoid arthritis (RA) and to develop a simple model for analysis of the cost-benefit of therapies. METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial, 162 patients with recent-onset RA who were available for the workforce were randomized to receive either a combination of three disease-modifying anti-rheumatic drugs (DMARDs) or a single DMARD for 2 years and were followed up for 5 years. No biological drugs were used. Data on sick leave and RA-related disability pensions came from official register records. Loss of productivity was computed by both the human capital approach (HCA) and the friction cost approach (FCA). Functional capacity was assessed by the HAQ at baseline and at 6 months. RESULTS: Over 5 years, mean loss of productivity per year was EUR 8344 by the HCA and EUR 1928 by the FCA. The level of the HAQ index at 6 months, but not the change in HAQ from baseline, determined productivity costs. With the HCA, a monotonous association between annual loss of productivity and the 6-month HAQ was found: EUR 2087 [95% confidence interval (CI) 1340-2903] per one step (0.13) on the HAQ scale from 0 to 1.88. With the FCA, the increase in loss of productivity was cut at the HAQ level of 0.5 to 0.75 (EUR 17 740 in 5 years). CONCLUSION: The HAQ index at 6 months may serve as a determinant of long-term RA-related indirect costs in economic analyses in early RA.

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.

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.