Rheumatoid Arthritis: Hakala M

Niemelä RK, Hakala M. · Department of Internal Medicine, University of Oulu, Finland. · Semin Arthritis Rheum. · Pubmed #10468410 No free full text.

Abstract: OBJECTIVE: Central nervous system (CNS) involvement in primary Sjögren's syndrome (pSS) is controversial with regard to frequency, significance, and etiology. METHODS: We describe a young woman with pSS and severe CNS disease and review the literature on the pathophysiology, clinical significance, symptoms, diagnostic examinations, and treatment of CNS disease with concomitant pSS (CNS-SS). RESULTS: Our patient with pSS had a 5-month history of benign lymphadenopathy and myositis, after which she developed severe CNS disease, vasculitic lesions on her hands, and a neurogenic bladder attributable to spinal cord involvement. The diagnosis was based on the clinical picture and the results of a brain magnetic resonance imaging (MRI) scan, electroencephalography (EEG), and cerebrospinal fluid (CSF) analysis. The disease did not respond to corticosteroids, but the administration of cyclophosphamide resulted in recovery. In the literature, the incidence of CNS-SS varies widely, from rare to incidence rates of 20% to 25%. The clinical picture is diverse, ranging from mild cognitive symptoms to fatal cerebrovascular accidents. The pathophysiology of CNS-SS is unclear, specific diagnostic methods are not available, and diagnosis is based on the clinical picture and a combination of examinations. MRI is the most sensitive test and cerebral angiography the most specific. CSF reflects involvement of the leptomeninges, and EEG is nonspecific. There are no controlled studies of the treatment of CNS-SS. Regimens for vasculitis are commonly used. CONCLUSIONS: CNS-SS is uncommonly recognized and difficult to diagnose. Increasingly accurate and available diagnostic examinations will yield more information about the association of CNS disease with pSS.

Parkkila TJ, Belt EA, Hakala M, Kautiainen HJ, Leppilahti J. · Rheumatism Foundation Hospital, Heinola, Finland and Department of Surgery, Oulu University Hospital, Oulu, Finland. · J Hand Surg Br. · Pubmed #15936131 No free full text.

Abstract: The purpose of this study was to compare the incidence of radiographic osteolysis following insertion of 89 Swanson and 126 Sutter metacarpophalangeal implants in rheumatoid arthritis patients. The mean follow-up time in the two groups of patients was 57 (40-80) and 55 (36-79) months, respectively. This paper proposes a new method of classifying radiographic osteolysis. The remarkable number of osteolytic changes seen in the bones adjacent to MCP prostheses in this study would suggest that silastic prostheses should only be used when other surgical alternatives cannot be used and that long-term control by radiography be maintained after implantation of silicone prostheses into the MCP joint. In all grades of our classification, osteolysis was more frequent in the Sutter than in the Swanson group in this study, suggesting that use of the Sutter rather than the Swanson implant is questionable.

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.

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.

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.

Hakala M, Pentikäinen PJ. · Reumasäätiön sairaala 18120 Heinola. · Duodecim. · Pubmed #12370987 No free full text.

This publication has no abstract.

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.

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.

Immonen K, Finne P, Hakala M, Kautiainen H, Pettersson T, Grönhagen-Riska C. · Departments of Medicine, North-Karelia Central Hospital, Joensuu and Helsinki University Central Hospital, Helsinki, Finland. · J Rheumatol. · Pubmed #18609734 No free full text.

Abstract: OBJECTIVE: To assess the incidence and outcome of renal replacement therapy (RRT) among patients with amyloidosis associated with inflammatory rheumatic diseases. METHODS: Patients with amyloidosis entering RRT from 1987 to 2002 were identified from the Finnish Registry for Kidney Diseases. Five hundred two patients were identified, 80% of whom had amyloidosis associated with an underlying rheumatic disease. They were followed from the time of entering RRT until death or until the end of 2003 using the Finnish national mortality files. RESULTS: During the study period, there was no decline in the number of patients with amyloidosis entering RRT. Mean age of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) increased significantly from 1987 to 2002 (p < 0.001). Male sex and a diagnosis of JIA indicated an increased risk of mortality. The median survival time after entering RRT was 2.11 years for RA (95% CI 1.93 to 2.69), 2.37 years for ankylosing spondylitis (95% CI 1.11 to 4.31), and 3.05 years for JIA (95% CI 2.19 to 4.23). The 5-year survival rates among patients with the corresponding diagnoses were 18% (95% CI 14% to 23%), 30% (95% CI 14% to 48%), and 27% (95% CI 14% to 41%), respectively. CONCLUSION: No decline was seen in the number of patients with amyloidosis associated with inflammatory rheumatic diseases accepted for RRT, but over the years, the age of patients with RA or JIA entering RRT was seen to increase. The outcome of patients with amyloidosis and endstage renal disease associated with rheumatic diseases remains poor.

Hakala M, Risteli J, Aman S, Kautiainen H, Korpela M, Hannonen P, Leirisalo-Repo M, Laasonen L, Paimela L, Möttönen T, Anonymous00099. · Rheumatism Foundation Hospital, Heinola, Finland. · Scand J Rheumatol. · Pubmed #18415764 No free full text.

Abstract: OBJECTIVE: To assess whether serum C-terminal cross-linking telopeptide of type I collagen (ICTP), a marker of type I collagen degradation, has any additional value in the assessment of treatment effect in patients with early rheumatoid arthritis (RA). METHODS: A total of 182 patients were randomized to treatment either with three disease-modifying anti-rheumatic drugs (DMARDs) and low-dose prednisolone (COMBI) or with a single DMARD with or without low-dose prednisolone (SINGLE). We investigated the prognostic value of serum ICTP level for the progression of joint destruction in X-rays (Larsen's score) from baseline to 2 years. RESULTS: There was a statistically significant decrease in serum ICTP levels from baseline to 1 year. At 6 months, the serum ICTP level was lower in the COMBI patients compared to that of the SINGLE cases (p = 0.008, after adjustment for baseline ICTP). When grouping the patients according to serum ICTP tertiles at 6 months, there was a statistically significant trend for increasing median change in Larsen score from baseline to 2 years from lowest to highest ICTP tertile in the SINGLE patients [p = 0.008, after adjustment for 28-joint Disease Activity Score (DAS28) score and RF status at baseline], while in the COMBI, the change remained low in all ICTP tertiles. CONCLUSIONS: The COMBI strategy for recent-onset RA results in early suppression of type I collagen degradation, which is reflected in radiological joint damage at 2 years. Serum ICTP at 6 months may be useful for identifying those RA patients whose treatment should be intensified to prevent further joint damage.

Jäälinoja J, Nissilä M, Kauppi MJ, Hakala M, Laiho K, Karttunen R, Hörkkö S, Ala-Kokko L. · Collagen Research Unit, Biocenter Oulu, Oulu, Finland. · J Rheumatol. · Pubmed #18381798 No free full text.

Abstract: OBJECTIVE: To measure the presence of autoantibodies binding to intact human recombinant collagen IX and assess their usefulness as a diagnostic marker and an indicator of disease activity in rheumatoid arthritis (RA). METHODS: Recombinant human full-length collagen IX (rCIX) was produced in a baculovirus expression system and purified for use in ELISA developed to detect antibodies to native and denatured collagen IX. Fifty-three patients with recent-onset rheumatoid factor-seropositive RA were analyzed for the presence of rCIX antibodies of the IgG type at the time of initial diagnosis and after 3, 6, 12, and 24 months of followup. The RA sera were accompanied by 30 controls. Associations were determined between patients' antibody titers, development of erosions in the hands and feet, and various clinical and laboratory markers. RESULTS: Serum antibody levels among patients with RA at time of diagnosis were 1.78 times higher against native rCIX (p < 0.001) and 1.71 times higher against denatured rCIX (p < 0.001) than in the controls, and they remained high during the followup. No correlation was seen between antibody levels and clinical and laboratory findings. CONCLUSION: Our data show that patients with recent-onset RA have significantly elevated levels of autoantibodies to human rCIX. These autoantibodies were observed already at the early stages of the disease, which may reflect their diagnostic potential in RA.

Immonen K, Savolainen A, Kautiainen H, Hakala M. · Department of Medicine, North Karelia Central Hospital, Joensuu, Finland. · J Rheumatol. · Pubmed #18381779 No free full text.

Abstract: OBJECTIVE: To determine the outcome of amyloidosis associated with juvenile idiopathic arthritis (JIA) in a hospital-based series. METHODS: Patient registers and amyloidosis biopsy files of the Department of Pediatrics of Rheumatism Foundation Hospital, the main tertiary center for inflammatory joint disorders in children in Finland, were scrutinized from 1976 to the end of 2003 to look for amyloidosis in patients under age 19 years. Medical records were reviewed and patients were interviewed by telephone. The causes of any deaths were obtained from death certificates. RESULTS: Twenty-four patients under age 19 years with biopsy-proven amyloidosis were found. As a sign of renal disease at the time of diagnosis of amyloidosis, 16 patients (67%) had proteinuria, but none had renal insufficiency. The 5-year survival rate of the series was 87.5% (95% CI 75% to 100%), and 10-year survival was 75% (54% to 92%). Ten patients (42%) out of the 24 died during a mean followup of 15.4 (range 1.5-27.6) years. The main cause of death was related to JIA in all patients but one. Patients treated with prednisolone alone from the diagnosis of amyloidosis onward had a mortality rate significantly higher than those taking disease modifying antirheumatic drugs and/or cytostatics (p = 0.001). At the end of followup, 14 patients (58%) were alive, 12 with normal renal function (3 of them had undergone renal transplantation), one had renal insufficiency, and one proteinuria. Proteinuria disappeared in 4 patients who were proteinuric (2 with nephrotic syndrome) at baseline, and their renal function remained normal. All the live patients had completed at least the 9 years of compulsory education, and 4 had academic degrees. Two female patients had delivered healthy children. CONCLUSION:The outcome of JIA-associated amyloidosis is poor. However, renal disease regressed in some patients under vigorous treatment. Successful treatment makes an active life possible for these patients.

Koivula MK, Savolainen E, Kaipiainen-Seppänen O, Kautiainen H, Luosujärvi R, Hakala M, Risteli J. · Department of Clinical Chemistry, P.O.Box 5000, FI-90014 University of Oulu, Oulu, Finland. · Rheumatology (Oxford). · Pubmed #18356174 No free full text.

Abstract: OBJECTIVE: To assess the specificity and sensitivity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series. METHODS: A cohort of 146 patients from the Kuopio 2000 Arthritis Survey having RA, AS, PsA, ReA, uSpA or undifferentiated arthritis were studied. Autoantibodies binding citrullinated types I and II carboxytelopeptides were measured in two different inhibition ELISA assays. Sera from 135 adult persons were used as controls. RESULTS: In RA, the sensitivities were 0.83 with long type I telopeptide and 0.78 with long type II telopeptide and the respective specificities were 0.94 and 0.93, while the corresponding values in other inflammatory joint diseases were much lower. The likelihood ratio in RA increased with longer peptides from 4.20 to 14.06 for type I telopeptide and from 2.74 to 11.67 for type II telopeptide. CONCLUSION: The antibody assay using long telopeptide from type I collagen was the most specific and sensitive method in every diagnostic category, although in the arthritides other than RA, binding was much less abundant and possibly citrulline-independent.

Uutela T, Kautiainen H, Hakala M. · Department of Internal Medicine, Central Hospital of Lapland, Rovaniemi, Finland. · Clin Exp Rheumatol. · Pubmed #18328145 No free full text.

Abstract: OBJECTIVE: There is a consensus on the need for a more thorough assessment of outcome of RA from the perspective of those who experience the disease. Our objective was to assess the health- related quality of life (HR-QOL) of RA patients by the Nottingham Health Profile (NHP), the measurement of subjective experienced distress. METHODS: One hundred and nineteen consecutive out-patients were cross-sectionally assessed. HR-QOL was evaluated by using the first section of the NHP, a generic quality of life instrument, that assess subjective distress on six dimensions: mobility, pain, energy, sleep, emotional reaction and social isolation. Functional capacity was measured by the Health Assessment Questionnaire (HAQ). RESULTS: The NHP scores for mobility, pain, energy and sleep showed a linear association (p<0.001 for each) with HAQ disability level. In addition to pain, patients with mild disability (HAQ 0-1) may suffer from remarkable fatigue (loss of energy) and problems in sleep. Even at the HAQ level 0, there was some perceived distress in almost all of the NHP dimensions. CONCLUSIONS: Poor HAQ levels were associated with patient perceived distress in dimensions which are getting minor attention in clinics, i.e., energy and sleep. It is to be noted that RA patients who reported no disability or its lowest levels measured by HAQ perceived notable distress in many NHP dimensions. Our results suggest that NHP is a potential candidate for a HR-QOL questionnaire which should considered to be used in routine clinical assessment of RA patients.

Eklund KK, Leirisalo-Repo M, Ranta P, Mäki T, Kautiainen H, Hannonen P, Korpela M, Hakala M, Järvinen P, Möttönen T. · Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki, Finland. · Clin Exp Rheumatol. · Pubmed #18078614 No free full text.

Abstract: OBJECTIVE: To study interleukin (IL)-1beta levels in recent onset RA patients treated either with combination DMARD therapy (sulfasalazine, methotrexate, hydroxychloroquine) or a single DMARD therapy. METHODS: Serum IL-1beta levels were measured before the treatment and 6 months after the institution of either single or combination DMARD therapy using a high sensitivity ELISA method. Radiographic evaluation of the hands and feet was performed at 0 and 24 months. RESULTS: Significant correlations (r = 0.28, 95% CI 0.10-0.45) were found between IL-1beta levels measured at 0 and 6 months. The IL-1beta levels at 0 months correlated significantly (r = 0.23, 95% CI 0.03-0.4, p= 0.021) with the baseline number of eroded joints at 0 months but not with radiographic joint damage at 24 months. The baseline level of IL-1beta was a better indicator for the presence of eroded joints than the baseline level of serum CRP. No significant changes in IL-1beta levels were observed during the first 6 months of anti-rheumatic treatment in either group. No statistically significant difference between IL-1beta levels in the patients with or without the shared epitope could be observed. CONCLUSIONS: The serum IL-1beta level is significantly associated with the presence of erosions at the onset of RA but its predictive value is attenuated or lost when single or combination DMARD medication is instituted. Measuring IL-1beta at the time of diagnosis in a single patient cannot be used to estimate the erosive nature of the disease or the prognosis.

Hämäläinen H, Kaarela K, Kröger H, Kauppi M, Järvenpää S, Hakala M, Kotaniemi A. · Department of Physical Medicine and Rehabilitation, Heinola, Finland. · Joint Bone Spine. · Pubmed #17905634 No free full text.

Abstract: OBJECTIVE: To ascertain changes in axial bone mineral in premenopausal women with severe rheumatoid arthritis (RA) treated with and without prednisolone (PRED), we conducted a two-year follow-up study of axial bone mineral density (BMD) and bone mineral content (BMC). METHODS: Premenopausal RA women (n=74) attending wards in the Rheumatism Foundation Hospital, Heinola, Finland were consecutively recruited for a follow-up study of BMD. BMD measurements in the lumbar spine and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry at baseline and after two years. BMD is expressed as BMC per projectional area g/cm2. The Larsen score of 0-100 was assessed at the check-ups. Two RA groups were analyzed: patients receiving prednisolone (n=48), RA with PRED group and without prednisolone (n=26), RA without PRED group. The control group (n=43) comprised age-matched, premenopausal healthy women. RESULTS: The patients in the RA with PRED group had lower BMD values than those in the RA without PRED group at commencement of follow-up. The mean weight-adjusted BMD percentage change in the lumbar spine to two years was -1.5% in the RA with PRED group, +0.6% in the RA without PRED group and -0.6% among the controls; a significant difference (P=0.030) was found between the RA groups. The mean BMC percentage change to two years in the lumbar spine was -2.2% in the RA with PRED-group (P=0.003), +0.0 in the RA without PRED-group and -0.6% in the control group. Accordingly, the mean weight-adjusted BMD percentage change in the femoral neck to two years was -2.6% in the RA with PRED group, +0.4% in the RA without PRED group and -0.9% among the controls; the difference between the RA groups being again significant (P=0.049). The mean BMC percentage change to two years in the femoral neck was -1.9% (P=0.006), -0.4% and -0.8%, respectively. Mean BMD decreased significantly in both lumbar spine (P=0.002) and femoral neck (P<0.001) only in the RA with PRED group. However, in spite of statistical findings above, when BMD is expressed as BMC per projectional area there was no statistically significant difference between the three groups in the change in BMC or projectional area in the lumbar spine or femoral neck. There was no significant correlation between the change in BMD in lumbar spine or femoral neck and the change in Larsen score among the RA groups. CONCLUSIONS: We conclude that according to BMC, premenopausal RA women both with and without prednisolone treatment and controls lost bone statistically similarly. It seems that the role of RA itself in the multifactorial development of axial bone mass during the first decade of severe RA is not the most essential issue. We assume that this role will be less important with better treatment of RA than our patients received. The amount of bone loss during treatment with low-grade prednisolone remains controversial.

Levälampi T, Honkanen V, Lahdenne P, Nieminen R, Hakala M, Moilanen E. · The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland. · Scand J Rheumatol. · Pubmed #17657672 No free full text.

Abstract: OBJECTIVE: Infliximab is effective and well tolerated in the treatment of juvenile idiopathic arthritis (JIA). The aim of the present study was to measure circulating levels of inflammatory mediators in patients with JIA during treatment with infliximab. METHODS: Eight patients with active JIA refractory to standard treatments were treated with infliximab (3-4 mg/kg) at weeks 0, 2 and 6 and thereafter at approximately 6-week intervals up to 24 weeks. RESULTS: All patients (n = 8) responded to the treatment. By 6 weeks of treatment the number of active joints had reduced from 16+/-4 (mean+/-SEM) to 4+/-1 (p<0.01) and C-reactive protein (CRP) levels had fallen from 31+/-8 to 8+/-3 (p<0.001). Infliximab treatment also reduced the serum concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO), and soluble adhesion molecules ICAM-1 (intercellular adhesion molecule-1), and E-selectin. Tumour necrosis factor-alpha (TNFalpha) levels tended to increase while the concentrations of endogenous TNF antagonists (sTNF-RI and sTNF-RII) reduced in most patients during treatment. CONCLUSIONS: Infliximab reduced serum levels of IL-6, MPO and soluble adhesion molecules in JIA patients, producing a good clinical response to the treatment.

Laivoranta-Nyman S, Möttönen T, Hannonen P, Korpela M, Kautiainen H, Leirisalo-Repo M, Julkunen H, Luukkainen R, Hakala M, Vuori K, Laine AP, Toivanen A, Ilonen J, Anonymous00074. · Turku Immunology Centre and Department of Virology, University of Turku. · Clin Exp Rheumatol. · Pubmed #17207378 No free full text.

Abstract: OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.

Parkkila T, Hakala M, Kautiainen H, Leppilahti J, Belt EA. · Rheumatism Foundation Hospital, Heinola, Finland. · Scand J Plast Reconstr Surg Hand Surg. · Pubmed #17065120 No free full text.

Abstract: Our aim was to evaluate the incidence and degree of osteolysis in a prospective series of patients with rheumatoid arthritis operated on with Sutter implants. Eighty-seven of the 110 operated hands (104 patients) with 282 implants were evaluated after a mean of 5.7 years (2.1-7.4). Osteolytic changes were present in 142 (50%) of the metacarpal and 152 (54%) of the phalangeal bones. Twenty-six of the metacarpal (9%) and 36 of the proximal phalangeal (13%) bones had osteolytic changes that did not affect the cortical bone. Cortical invasion was recorded in 100 (35%) of the metacarpal and 103 (37%) of the proximal phalangeal bones. The cortex was perforated in both bones in 14 (5%). Osteolytic changes were related to fractures of implants and to the dominant hand, but not to pain. Surgeons who operate on patients with rheumatoid diseases should note that silicone rubber implants often cause osteolytic changes.

Palosaari K, Vuotila J, Takalo R, Jartti A, Niemelä RK, Karjalainen A, Haapea M, Soini I, Tervonen O, Hakala M. · Department of Diagnostic Radiology, Oulu University Hospital, Kajaanintie 50, FIN-90029, BOX 50, Oulu, Finland. · Rheumatology (Oxford). · Pubmed #16670155 links to  free full text

Abstract: OBJECTIVES: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA). METHODS: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome. RESULTS: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage. CONCLUSION: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.

Koivula MK, Aman S, Alasaarela E, Karjalainen A, Hakala M, Risteli J. · Department of Clinical Chemistry, University of Oulu, PL 5000, FI-90014 Oulun yliopisto, Finland. · Rheumatology (Oxford). · Pubmed #16632481 links to  free full text

Abstract: OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II collagens inhibit the binding of autoantibodies to the respective antigens immobilized onto solid phase, and to use modifications of previous methods to re-analyse rheumatoid arthritis (RA) and control serum samples. METHODS: Autoantibody binding was inhibited with normal or citrullinated carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods. Serum samples were available from 120 patients with RA and 81 controls. RESULTS: Autoantibodies that bind normal C-telopeptides were not inhibited with soluble normal or citrullinated telopeptides. However, the antibodies that bind only citrullinated telopeptides could be inhibited with corresponding citrullinated telopeptides. Thus, it is not necessary to study the binding of autoantibodies to normal collagens if the specificity of their binding is assessed by immunological inhibition. For type I telopeptide, there are two arginines, the latter of which, when citrullinated, is important for binding. For type II telopeptide, there is one arginine, which is important when citrullinated. The other amino acids, e.g. the last alanine, have only a slight effect on binding. These improved methods differentiate better between RA patients, who have specific citrullinated autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on inhibition assay, it is possible to measure the autoantibodies binding specifically to citrullinated telopeptides of type I and II collagens. When only one assay is involved, variance is decreased and the overall performance is easier than before.