Rheumatoid Arthritis: Kvien TK

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

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

Kalden JR, Scott DL, Smolen JS, Schattenkirchner M, Rozman B, Williams BD, Kvien TK, Jones P, Williams RB, Oed C, Rosenburg R, Anonymous00047. · Department of Internal Medicine III, University of Erlangen-Nuremberg, Germany. · J Rheumatol. · Pubmed #11550964 No free full text.

Abstract: OBJECTIVE: We previously reported that the new disease modifying antirheumatic drug leflunomide resulted in significant improvement in functional ability compared with placebo and sulfasalazine in a 6 month double blind, randomized, Phase III trial in rheumatoid arthritis (RA). The current study compared functional disability in cohorts of patients with RA from the initial study who volunteered to continue treatment with leflunomide or sulfasalazine. METHODS: The Health Assessment Questionnaire (HAQ) was used to assess functional ability in patients completing 6 months of therapy who chose to continue in double blinded 12 and 24 month extensions. Patients on active regimens continued taking leflunomide 20 mg/day or sulfasalazine 2 g/day; those taking placebo were switched at Month 6 to sulfasalazine. RESULTS: Leflunomide significantly improved patients' functional ability compared to placebo (p < or = 0.0001) and sulfasalazine (p < or = 0.01) at 6 months. These changes were seen as early as Month 1, and continued improvements were seen in 12 and 24 month cohorts. Mean HAQ scores were significantly improved with leflunomide compared with sulfasalazine at 24 months (-0.65 vs -0.36; p = 0.0149); corresponding changes in HAQ Disability Index (DI) were -0.73 vs -0.56 and were not statistically different. Leflunomide is safe and well tolerated and no unexpected adverse events were noted during the 2 year period; diarrhea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION: These longterm data confirm leflunomide improves functional ability as shown by reductions in HAQ scores. The benefit of leflunomide is reflected in other efficacy criteria, such as global assessments and the American College of Rheumatology response rates, all of which showed significantly more improvement with leflunomide than sulfasalazine at 24 months.

Emery P, Kvien TK. · No affiliation provided · BMJ. · Pubmed #17626917 No free full text.

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Kvien TK, Mikkelsen K, Nordvåg BY. · No affiliation provided · J Rheumatol. · Pubmed #12784381 No free full text.

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Kvien TK. · No affiliation provided · Rheumatology (Oxford). · Pubmed #11886956 links to  free full text

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Lillegraven S, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Best Pract Res Clin Rheumatol. · Pubmed #17870030 No free full text.

Abstract: Rheumatoid arthritis is a chronic inflammatory disease with a major impact on physical and psychological health. It can cause severe disability and reduce health-related quality of life, aspects that are important to patients. Thus, it is important to measure disability and health-related quality of life in clinical practice and in clinical trials. This article presents an overview of the most important measures of outcome concerning disability and health-related quality of life, including different forms of the Health Assessment Questionnaire (HAQ, MHAQ, MDHAQ, HAQ II), visual analogue scales for fatigue and function, SF-36, Arthritis Impact Measurement Scales (AIMS/AIMS2), the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire, Nottingham Health Profile, Sickness Impact Profile and the utility instruments 15D, EQ-5D, SF-6D and Health Utilities Index (HUI) 2 and 3.

Keeling SO, Landewe R, van der Heijde D, Bathon J, Boers M, Garnero P, Geusens P, El-Gabalawy H, Inman RD, Kraus VB, Kvien TK, Mease PJ, Ostergaard M, Ritchlin C, Syversen SW, Maksymowych WP. · Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #17343310 No free full text.

Abstract: OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. CONCLUSION: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA.

Skomsvoll JF, Wallenius M, Koksvik HS, Rødevand E, Salvesen KA, Spigset O, Kvien TK. · Department of Obstetrics, Trondheim University Hospital, Trondheim, Norway. · Nat Clin Pract Rheumatol. · Pubmed #17334338 No free full text.

Abstract: Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti-TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk-benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible.

Kvien TK, Uhlig T. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Scand J Rheumatol. · Pubmed #16234180 No free full text.

Abstract: Assessment of health-related quality of life (HRQoL) is relevant for the patients and is important in both clinical research and daily clinical practice. Generic and disease-specific instruments for assessment of HRQoL are reviewed. Changes in HRQoL provide important information on randomized controlled clinical trials as well as on observational studies. The floor effect is a limitation of many of the scales, especially in patients with less severe disease. Feasibility and low test-retest reproducibility limit the use of many of the instruments in clinical practice, especially when they are used for individual treatment decisions. Electronic transferral of data from patients to the health professionals by, for example, internet or a personal digital assistant (PDA), opens up new opportunities for frequent patient reports and improved access to the data.

Uhlig T, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #15286008 links to  free full text

Abstract: During the past decades a number of studies have examined the incidence of rheumatoid arthritis (RA) in different geographical settings and at different times. Some studies from the 1970s and 1980s reported a higher incidence of RA than seen during recent years, where reported incidence numbers seems to have flattened out at a lower level. Besides a real time dependent decline of RA incidence, changing methodology in classification may be an equally important explanation. Today we may assume that annually 25-50 people from a population of 100,000 will develop typical RA.

Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Pharmacoeconomics. · Pubmed #15157000 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, generally progressive autoimmune disease that causes functional disability, significant pain and joint destruction, and leads to premature mortality. It is estimated to affect between 0.5 and 1.0% of the adult population worldwide, increases in prevalence with age and affects more women than men. The magnitude of the severe long-term economic consequences of RA has been underestimated in the past. Most patients with the disease require continuous treatment to retard or stop progression and to control disease flares. Many also require surgery, such as total hip or knee replacement. In addition to these direct costs, work disability leads to reduced productivity and early retirement, and as a result, substantial indirect costs. The individual and his or her family must cope with the feeling of loss of contribution to society combined with redefined social roles, and the effects of pain, fatigue, low self-esteem, mental distress and depression. A number of countries in North America and Europe have reported a decline in the incidence of RA in recent years, although geographical differences remain that may be associated with genetic, environmental or cultural factors. Nevertheless, patients with RA have not shared the improvements in survival rates seen with other diseases over the last 40 years, and have a mean reduction in life expectancy of between 5 and 10 years. Disease severity, activity and disability are strongly linked to premature mortality in patients with RA. The high direct and indirect costs associated with RA, together with the substantial morbidity and mortality affecting millions of people worldwide, underline the potential benefits of improved treatments for this chronic disease to patients, their families and society.

Kvien TK, Uhlig T. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Clin Exp Rheumatol. · Pubmed #14969062 No free full text.

Abstract: The Oslo experience with early rheumatoid arthritis (RA) is based on studies performed within the setting of a register of RA patients and of the longitudinal follow-up of patients with early RA. This article discusses some relevant issues for research on early arthritis: whether the current RA classification criteria are appropriate, the shift in incidence toward elderly patients, and the heterogeneity of the disease. Our data clearly show that 3 of the items of the classification criteria are infrequently fulfilled early in the disease and that RA most frequently starts after the age of 60. Our data also suggest that disease onset may be defined either as symptom onset or as when the classification criteria are fulfilled. The choice between these 2 options does not seem to influence the longitudinal results.

Johnsen V, Førre Ø, Haga HJ, Kvien TK, Mikkelsen K, Nordvåg BY, Rødevand E. · Revmatologisk avdeling, Sørlandet sykehus, 4604 Kristiansand. · Tidsskr Nor Laegeforen. · Pubmed #12822010 links to  free full text

Abstract: BACKGROUND: During the last decade patients with active rheumatoid arthritis have been offered early and aggressive drug therapy in order to decrease the damaging effect of inflammation on cartilage and bone. Combination of two or more disease-modifying antirheumatic drugs has been used more frequently to achieve better efficacy than with monotherapy without increasing drug side effects. MATERIALS AND METHODS: We have studied available rheumatological literature to find the best documented drug combinations. RESULTS: The combination of methotrexate, sulfasalazine and hydroxychloroquine seems to be a well documented alternative, and so is the combination of methotrexate and cyclosporine. Modern biologic drugs like etanercept, infliximab and anakinra work best in combination with methotrexate. INTERPRETATION: The combination of two or more disease-modifying antirheumatic drugs can be a good alternative to monotherapy in the treatment of patients with active rheumatoid arthritis, either when monotherapy has failed or unacceptable side effects have occurred, or as a first choice in patients who need very early and aggressive therapy. Combination therapy should only be initiated by a rheumatologist, after informed consent. A safe clinical and chemical monitoring must be organized in cooperation with the patient and the primary physician.

Haugeberg G, Ørstavik RE, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Norway. · Curr Opin Rheumatol. · Pubmed #12819477 No free full text.

Abstract: The effects of rheumatoid arthritis on bone include structural joint damage (erosions) and osteoporosis. The latter may lead to increased risk for fractures, which are associated with increased morbidity and mortality. Osteoporosis in rheumatoid arthritis is characterized by a complexity of risk factors, including primary osteoporosis risk factors in addition to inflammation, immobilization, and use of corticosteroids. Quantitative assessment of periarticular and generalized bone loss in rheumatoid arthritis may be reliable indicators of future disease course and potential response variables in intervention studies. The osteoclast cell in rheumatoid arthritis plays a crucial role in the development of erosions and periarticular and generalized osteoporosis, suggested to be mediated through the osteoprotegerin/receptor activator of Nuclear Factor (NF)-kappabeta/receptor activator of NF-kappabeta ligand signaling system. Based on an improved understanding of this biology, new treatment opportunities exist.

Kvien TK, Heiberg T. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · J Rheumatol. · Pubmed #12672219 No free full text.

Abstract: Health status measures constitute an essential part of outcome assessments in patients with rheumatic diseases. Currently used health status measures typically assess patient perceptions within various dimensions of health. The issue of widening patient perspective in outcome assessments was raised at OMERACT 2000 and further activities were initiated at the subsequent American College of Rheumatology meetings. Measuring patient perceptions of health is considered the standard approach in clinical practice, controlled clinical trials, and longitudinal observation studies, as well as in other types of epidemiological research. However, the traditionally used instruments also have limitations based on the relevance of the questionnaire items, sensitivity to change in longitudinal observational studies, and intraindividual variations over time. Patient priorities or preferences for improvement in health may be an alternative for the assessment of important patient outcomes. Data support that patient priorities for improvement in health are associated with their perception, but that overlap is incomplete and that complimentary information may be achieved. Expectations about future health and satisfaction with health may also represent alternative approaches. Thus, an open research agenda is required for the future, including different approaches regarding both endpoints and methodological issues.

Uhlig T, Finset A, Kvien TK. · National Resource Center for Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Curr Opin Rheumatol. · Pubmed #12598801 No free full text.

Abstract: Comprehensive rehabilitation involving multidisciplinary involvement of healthcare professionals is available to patients with rheumatic diseases. Studies were reviewed on the effectiveness of such programs for patients with chronic low back pain, widespread pain, and rheumatoid arthritis. When effects on the various outcome measures are demonstrated, improvements can only with difficulty be attributed to a specific component of a comprehensive program. Economic analyses for the effectiveness of comprehensive programs are scarce, but are needed by policy makers to allow optimal allocation of resources. Preferably the overall performance of comprehensive rehabilitation programs, not the individual components, should be evaluated.

Rødevand E, Kvien TK, Johnsen V. · Revmatologisk avdeling Regionsykehuset i Trondheim 7006 Trondheim. · Tidsskr Nor Laegeforen. · Pubmed #11876141 No free full text.

Abstract: BACKGROUND: Leflunomide is a novel disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis. The agent has been developed for the treatment of rheumatoid arthritis, but its multiple immunomodulatory properties may in the future be of interest in the treatment of other rheumatic and immunological diseases. MATERIAL AND METHODS: Review of the literature in order to present the current relevant clinical documentation of the drug. RESULTS: The clinical documentation is mainly based on three large, prospective, randomized trials of six months "to two years" duration comparing leflunomide with placebo, sulphasalazine or methotrexate. The efficacy of leflunomide in all trials was superior to placebo and comparable to sulphasalazine and methotrexate. The frequency of adverse events was also comparable to the comparators. INTERPRETATION: Leflunomide is a safe and efficacious addition to the roster of antirheumatic drugs, but further clinical trials and experience from clinical practice are needed in the evaluation of its place as a disease-modifying agent.

Kvien TK, Uhlig T, Kristiansen IS. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Drugs. · Pubmed #11693461 No free full text.

Abstract: Tumour necrosis factor (TNF) antagonists or blocking agents represent a major advance in the treatment of rheumatoid arthritis (RA), but their use raises economic concerns because of the high drug cost. Population-based patient registers with clinical data allow the estimation of the proportion of patients with RA who are eligible for TNF antagonist therapy according to recent consensus statements on TNF-targeted therapy. Data were derived from a representative county-based (500,000 population) register of patients with RA. Of 894 patients aged between 18 and 70 years, 636 (71%) [females 80%, mean (SD) age 53.6 (12.2) years and mean (SD) disease duration 12.2 (9.3) years] had a clinical and radiographic examination. The eligibility for TNF-targeted therapy was estimated from the following criteria: (i) previous or current therapy with at least one disease-modifying antirheumatic agent (DMARD); and (ii) active disease. Disease activity criteria were set to 28-swollen joint count (28-SJC) > or = 6, 28-tender joint count > or = 6, and erythrocyte sedimentation rate (ESR) > or = 28 mm/hour or C-reactive protein (CRP) > or = 20 mg/L. Sensitivity analyses were performed varying some of these disease activity parameters. Of the 636 patients, as many as 526 (83%) had previously or were currently using DMARDs and 98 (15%) fulfilled both the DMARD and activity criteria, thus being the maximum number of patients considered for TNF-targeted therapy. If the most stringent criteria were used (ever DMARD, 28-SJC > or = 12 and ESR > or = 50 mm/hour or CRP > or = 40 mg/L) only 15 of the 626 (2%) would be candidates for TNF-targeted therapy. In a population of 1 million, assuming a prevalence of 2000 patients with RA under the age of 70 years, the number of candidates for TNF-targeted therapy would be 40 to 300, depending on the disease activity criteria. Stringent ESR and CRP criteria would lead to a major reduction in the number of eligible patients. These utilisation data imply annual drug costs in the range of $US 480,000 to $US 3,600,000 for TNF antagonists for RA per 1 million population. Further economic evaluations are needed to determine for which groups such treatment is warranted from a health economics perspective.

Haga HJ, Johnsen V, Østensen M, Mikkelsen K, Gulseth HC, Kvien TK, Nordvåg BY. · Revmatologisk avdeling Haukeland Sykehus 5021 Bergen. · Tidsskr Nor Laegeforen. · Pubmed #11187194 No free full text.

Abstract: The polymyalgic syndrome may be the presenting clinical feature for several diseases such as polymyalgia rheumatica, temporal arteritis, malignancy, rheumatoid arthritis, virus infections, connective tissue diseases, and myositis. In this review we present the various diagnostic options seen from a rheumatological point of view, with emphasis on polymyalgia rheumatica, temporal arteritis and the paraneoplastic syndrome. We are of the opinion that polymyalgia rheumatica is overdiagnosed in general practice, and steroid treatment may delay diagnosis and treatment of other differential diagnosis presenting as the polymyalgic syndrome. Several recently published Norwegian epidemiological studies offer new information on various aspects of the polymyalgic syndrome, which will be discussed.

Keystone E, Emery P, Peterfy CG, Tak PP, Cohen S, Genovese MC, Dougados M, Burmester GR, Greenwald M, Kvien TK, Williams S, Hagerty D, Cravets MW, Shaw T. · Division of Rheumatology, University of Toronto, Toronto, Canada. · Ann Rheum Dis. · Pubmed #18388156 No free full text.

Abstract: OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.

Heiberg MS, Rødevand E, Mikkelsen K, Kaufmann C, Didriksen A, Mowinckel P, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #16679432 No free full text.

Abstract: OBJECTIVES: To compare the effectiveness of adalimumab monotherapy and adalimumab and methotrexate (MTX) combination therapy in patients with established rheumatoid arthritis. METHODS: Data from an ongoing longitudinal observational study in Norway were used to compare response to treatment with two different adalimumab regimens (monotherapy, n = 84; combination with MTX, n = 99). Patients were assessed with measures of disease activity, health status and utility scores. Within-group changes were analysed from baseline to follow-up at 3 and 6 months and the changes were compared between groups after adjustment for the propensity score. The groups were also compared for the proportions of patients achieving European League Against Rheumatism (EULAR) good response, Disease Activity Score (DAS)28 remission and treatment terminations. RESULTS: The improvement from baseline was significant for all measures in the adalimumab and MTX group, but only for DAS28, joint counts, two Short-form Health Survey with 36 questions (SF-36) dimensions and patient's and investigator's global assessment in the monotherapy group. All between-group differences were numerically in favour of combination therapy and significant for C reactive protein, joint counts, DAS28, Modified Health Assessment Questionnaire, investigator's global assessment, four SF-36 dimensions and Short Form 6D at 6 months. More patients in the combination therapy group reached EULAR good response (p<0.001) and remission (p = 0.07). At 6 months, 80.8% of the patients in the combination therapy group and 59.5% in the monotherapy group remained on treatment (p = 0.002). More withdrawals in the monotherapy group were due to adverse events. CONCLUSIONS: Our results were consistent across several categories of end points and suggest that adalimumab combined with MTX is effective in patients with rheumatoid arthritis treated in daily clinical practice and is superior to adalimumab monotherapy.

Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF. · Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #16606653 No free full text.

Abstract: OBJECTIVES: To examine whether treatment with anti-tumour necrosis factor (TNF) alpha prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment. PATIENTS AND METHODS: 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, beta-isomerised carboxy terminal telopeptide of type 1 collagen (beta-CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks. RESULTS: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum beta-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in beta-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0-14 weeks interval. CONCLUSION: In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands.

Heiberg MS, Nordvåg BY, Mikkelsen K, Rødevand E, Kaufmann C, Mowinckel P, Kvien TK. · Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #16052584 links to  free full text

Abstract: OBJECTIVE: To compare the effectiveness of tumor necrosis factor (TNF)-blocking agents (etanercept and infliximab) in patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS). METHODS: Data from an ongoing longitudinal, observational study in Norway were used to assess changes in health-related quality of life (HRQOL) in patients with RA (n = 291) and AS (n = 62). Patients received anti-TNF therapy, and changes in scores on the Short Form 36 (SF-36), SF-6D, modified Health Assessment Questionnaire, and visual analog scales for patients' assessments of pain, fatigue, and global status from baseline to followup examinations at 3 and 6 months were compared. Data were adjusted for age, sex, and baseline values and are presented as crude estimates as well as standardized response means. RESULTS: Both groups had improvements in all measures at 3 and 6 months. At 3 months, the changes were significantly better in the AS group compared with the RA group for all measures except the SF-36 social functioning scores. At 6 months, all changes were numerically greater in the AS group. Differences were significant for the SF-36 role emotional scores and were borderline significant for the SF-36 physical functioning, role physical, and vitality scores and for the SF-6D scores. CONCLUSION: In this real-life setting, patients with AS experienced improvement in HRQOL that was comparable to, and sometimes greater than, that observed in RA patients. These results support the idea that patients with AS should have the same access to TNF-blocking agents as patients with RA.

Haugeberg G, Strand A, Kvien TK, Kirwan JR. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Arch Intern Med. · Pubmed #15956010 links to  free full text

Abstract: BACKGROUND: Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions. Prednisolone has been shown to reduce the rate of hand joint destruction as seen on radiography but has not been shown to reduce the rate of hand bone loss. METHODS: In a double-blind study comparing oral prednisolone (7.5 mg/d for 2 years) with placebo, hand bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years. RESULTS: The mean loss of hand bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up (-0.011 vs -0.022 g/cm(2)) (P = .005) and at the 2-year follow-up (-0.026 vs -0.039 g/cm(2)) (P = .03). The mean percentage group difference in loss of hand bone density was 2.8% (P = .004) at the 1-year follow-up and 3.5% (P = .01) at the 2-year follow-up. In the first year, C-reactive protein, a marker of inflammation, was strongly correlated with hand bone loss in placebo-treated patients but not in prednisolone-treated patients, suggesting that prednisolone breaks the link between bone loss and inflammation. CONCLUSIONS: To our knowledge, this is the first double-blind randomized study to show that disease-related loss of hand bone density in rheumatoid arthritis can be decelerated by prednisolone. This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect.

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.