Rheumatoid Arthritis: Hafström I

Svensson B, Hafström I. · Reumatologsektionen, Medicinkliniken, Helsingborgs lasarett. · Lakartidningen. · Pubmed #17212318 No free full text.

This publication has no abstract.

Klareskog L, Hafström I, Saxne T, Hedin PJ. · Reumatologiska kliniken, Karolinska sjukhuset, Stockholm. · Lakartidningen. · Pubmed #11187380 No free full text.

Abstract: During the present year more new drugs will be introduced for the treatment of rheumatoid arthritis than have been for several decades. In order to make the widening range of therapeutic options truly available in daily clinical care, certain changes will be required in the organization of treatment resources for rheumatic patients. Several articles in the present issue of Läkartidningen describe the new drugs. Besides introducing these new drugs, it is shown that combinations of "old" antirheumatic drugs (DMARD's) given in high doses and in an earlier phase of disease than previously also exert positive effects on disease course. Taken together, new strategies have been developed for the treatment of patients with RA. One such strategy, endorsed by the Swedish Rheumatology Association, is described in this paper, together with a description of a new national surveillance system for the new drugs.

Ernestam S, Lampa J, Rogberg S, Rönnelid J, Klareskog L, Hafström I. · Department of Rheumatology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. · J Rheumatol. · Pubmed #12913930 No free full text.

Abstract: OBJECTIVE: Intramuscular gold is a well documented treatment in rheumatoid arthritis (RA), but its mechanism of action is still poorly understood. From an observation that gold sodium thiomalate (GSTM) induces monocyte-derived interleukin 6 (IL-6) and IL-10 production in vitro, a hypothesis has been proposed that gold exerts its action mainly as a selective immunostimulator rather than as a general immunosuppressant. In this prospective study we investigated cytokine production in peripheral blood from patients with RA during treatment with GSTM. METHODS: A total of 20 patients with RA were treated with GSTM for at least 3 months. Disease activity was recorded at baseline, 12, 20, and 28 weeks. The ELISPOT method was used to measure spontaneous production of IL-6, IL-10, and interferon-g (IFN-g) from peripheral blood mononuclear cells (PBMC) at baseline and 4 and 12 weeks and production after incubation with GSTM in vitro, at different concentrations (0, 3, 12.5, 40 micro g/ml) at baseline. IL-6 and IL-10 concentrations in serum were measured with ELISA. RESULTS: The numbers of IL-10-producing cells were increased after 4 weeks' treatment with GSTM (p < 0.01). The numbers of cells spontaneously producing IL-6 were increased after 4 weeks (p < 0.01) and 12 weeks (p < 0.01). The numbers of IFN-g-producing cells were increased after 4 weeks (p < 0.01). Serum concentrations of IL-10 were increased after 4 weeks (p < 0.01). Serum concentrations of IL-6 were not changed at any timepoint. The in vitro effect of GSTM on IL-10 production from PBMC at baseline predicted development of skin reactions during GSTM treatment, with lack of skin reactions being associated with high gold induced IL-10 production (p < 0.05). There was no correlation between clinical response and cytokine production. CONCLUSION: This study indicates an immunostimulatory effect of GSTM treatment in patients with RA. The increase in IL-10 production during GSTM treatment may contribute to the positive effects of gold in RA.

Hafström I, Hallengren M. · Department of Rheumatology, Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden. · Scand J Rheumatol. · Pubmed #12737330 No free full text.

Abstract: OBJECTIVE: The objective was to prospectively evaluate the short as well as the long-term effects of intensive physiotherapy in a stable, sunny and warm climate on physical function and health related quality of life in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA). METHODS: Ninety-three Swedish patients with RA and SpA receiving physiotherapy for 4 weeks in Israel or Tenerife were followed for 6 months. Physical function was evaluated by the Swedish version of Stanford Health Assessment Questionnaire (HAQ) and quality of life by the Nottingham Health Profile (NHP) questionnaire. RESULTS: There were significant improvements in HAQ-scores and global NHP-scores as well as all subcategories of NHP immediately after the treatment abroad, effects that were still measurable after six months. At that time point nearly half of the patients had clinically meaningful reduction of HAQ-scores (> or = 0.25). CONCLUSION: Physiotherapy in a warm and stable climate, with many hours of daily sunshine, is a valuable treatment complement for Swedish patients with RA and SpA.

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.

Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, Brannemark S, Nylander I, Rönnelid J, Laasonen L, Klareskog L. · Department of Rheumatology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden. · Rheumatology (Oxford). · Pubmed #11600749 links to  free full text

Abstract: OBJECTIVE: Whether food intake can modify the course of rheumatoid arthritis (RA) is an issue of continued scientific and public interest. However, data from controlled clinical trials are sparse. We thus decided to study the clinical effects of a vegan diet free of gluten in RA and to quantify the levels of antibodies to key food antigens not present in the vegan diet. METHODS: Sixty-six patients with active RA were randomized to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 yr. All patients were instructed and followed-up in the same manner. They were analysed at baseline and after 3, 6 and 12 months, according to the response criteria of the American College of Rheumatology (ACR). Furthermore, levels of antibodies against gliadin and beta-lactoglobulin were assessed and radiographs of the hands and feet were performed. RESULTS: Twenty-two patients in the vegan group and 25 patients in the non-vegan diet group completed 9 months or more on the diet regimens. Of these diet completers, 40.5% (nine patients) in the vegan group fulfilled the ACR20 improvement criteria compared with 4% (one patient) in the non-vegan group. Corresponding figures for the intention to treat populations were 34.3 and 3.8%, respectively. The immunoglobulin G (IgG) antibody levels against gliadin and beta-lactoglobulin decreased in the responder subgroup in the vegan diet-treated patients, but not in the other analysed groups. No retardation of radiological destruction was apparent in any of the groups. CONCLUSION: The data provide evidence that dietary modification may be of clinical benefit for certain RA patients, and that this benefit may be related to a reduction in immunoreactivity to food antigens eliminated by the change in diet.

Elkan AC, Håkansson N, Frostegård J, Cederholm T, Hafström I. · Department of Rheumatology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. · Arthritis Res Ther. · Pubmed #19284557 links to  free full text

Abstract: INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA. METHODS: A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined. RESULTS: The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001). CONCLUSIONS: About one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD.

Tengstrand B, Carlström K, Hafström I. · Department of Rheumatology, Unit of Obstetrics and Gynecology, Division of ClinicalChemistry, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. · J Rheumatol. · Pubmed #19273455 No free full text.

Abstract: OBJECTIVE: To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs. METHODS: Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations. RESULTS: The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (r(s) = -0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity. CONCLUSION: In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.

Engvall IL, Svensson B, Tengstrand B, Brismar K, Hafström I, Anonymous00052. · Department of Rheumatology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. · Arthritis Res Ther. · Pubmed #18986531 links to  free full text

Abstract: INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density. METHODS: One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months. RESULTS: Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group. CONCLUSIONS: Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.

Hafström I, Albertsson K, Boonen A, van der Heijde D, Landewé R, Svensson B, Anonymous00040. · The Rheumatology Unit, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #18420939 No free full text.

Abstract: OBJECTIVE: To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage for a total of 4 years. METHODS: A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp-van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6. RESULTS: Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups. CONCLUSIONS: Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.

Elkan AC, Sjöberg B, Kolsrud B, Ringertz B, Hafström I, Frostegård J. · Rheumatology Unit, Karolinska Institutet at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. · Arthritis Res Ther. · Pubmed #18348715 links to  free full text

Abstract: INTRODUCTION: The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (anti-PCs). METHODS: Sixty-six patients with active RA were randomly assigned to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 year. Thirty patients in the vegan group completed more than 3 months on the diet regimen. Blood lipids were analyzed by routine methods, and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay. Data and serum samples were obtained at baseline and after 3 and 12 months. RESULTS: Mean ages were 50.0 years for the vegan group and 50.8 years for controls. Gluten-free vegan diet induced lower body mass index (BMI) and low-density lipoprotein (LDL) and higher anti-PC IgM than control diet (p < 0.005). In the vegan group, BMI, LDL, and cholesterol decreased after both 3 and 12 months (p < 0.01) and oxLDL after 3 months (p = 0.021) and trendwise after 12 months (p = 0.090). Triglycerides and high-density lipoprotein did not change. IgA anti-PC levels increased after 3 months (p = 0.027) and IgM anti-PC levels increased trendwise after 12 months (p = 0.057). There was no difference in IgG anti-PC levels. In the control diet group, IgM anti-PC levels decreased both after 3 and 12 months (p < 0.01). When separating vegan patients into clinical responders and non-responders at 12 months, the effects on oxLDL and anti-PC IgA were seen only in responders (p < 0.05). CONCLUSION: A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory, including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels.

Tengstrand B, Larsson E, Klareskog L, Hafström I. · Karolinska University Hospital/Huddinge, SE-141 86 Stockholm, Sweden. · Scand J Rheumatol. · Pubmed #17963164 No free full text.

Abstract: OBJECTIVE: Short-term, low-dose glucocorticoid (GC) treatment has anti-inflammatory and disease-modifying effects in rheumatoid arthritis (RA). However, scientific support for long-term, low-dose GC treatment, although widespread, is poor, and information on the effects on bone density is scarce. The aim of this study was to investigate how long-term GC treatment in RA affects inflammation as well as bone density, and also to investigate the feasibility of withdrawal of GC. PATIENTS AND METHODS: Fifty-eight patients with RA treated with 5-7.5 mg prednisolone daily for at least 2 years were randomized either to withdraw or to continue GC treatment. The patients were followed prospectively for 2 years with respect to disease activity [using the Disease Activity Score calculated for 28 joints, (DAS28)], functional ability [using the Health Assessment Questionnaire (HAQ) score] and bone mineral density (BMD) of the lumbar spine and hip. RESULTS: Only 11 patients out of 26 randomized to stop GC treatment and available for outcome measures succeeded in stopping the GC medication within 1 year. Fifteen patients failed withdrawal of GC because of increased joint symptoms. A higher mean DAS28 during the study was associated with loss of bone mass in the trochanter. The group that continued with unchanged GC treatment did not deteriorate in BMD during the 2 years but in fact Z-scores improved significantly. CONCLUSION: Our results indicate that low-dose GC treatment after several years has persisting anti-inflammatory effects in RA and no further negative impact on BMD. It thus seems to be more important to control disease activity than withdraw low-dose GC treatment in this population considering bone health.

Hafström I, Rohani M, Deneberg S, Wörnert M, Jogestrand T, Frostegård J. · Department of Rheumatology, Department of Cardiology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · J Rheumatol. · Pubmed #17696277 No free full text.

Abstract: OBJECTIVE: To determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA). METHODS: At start of the first disease modifying antirheumatic drug, 67 patients with early, active RA were randomized to either 7.5 mg prednisolone daily (n = 34) or no prednisolone (n = 33). In the prednisolone group, 21 were treated for 2 years and 13 continuously. After a mean of 5 years intima-media thickness (IMT) and calculated intima-media area (cIMa) of the carotid arteries were determined by B-mode ultrasound. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery. RESULTS: IMT [median (interquartile range) 0.675 mm (0.58-0.82) vs 0.673 mm (0.0.62-0.80)], cIMa [13.7 mm2 (11.45-20.37) vs 14.1 mm2 (12.34-17.38)], prevalence of atherosclerotic plaques (82.3% vs 81.9%), and endothelial function [FMD% (mean +/- SD) 3.88% +/- 2.8 vs 3.74% +/- 2.9] did not differ between patients treated with and those not treated with prednisolone. There were no differences in lumen diameter of carotid arteries, or levels of lipoproteins, glucose, and blood pressure. Patients treated for at least 4 years (and currently treated) with prednisolone had a trend to higher systolic blood pressure (157 +/- 29 mm Hg) compared with untreated patients (141 +/- 28 mm Hg; p = 0.06) and had higher cholesterol levels (5.6 mmol/L +/- 1.39 vs 4.9 +/- 28; p = 0.03). In the whole cohort, age and HDL were independently associated with IMT; age, HDL, and blood pressure with cIMa; and age and serum creatinine with presence of atherosclerotic plaques. CONCLUSION: Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA. However, total cholesterol was higher in patients treated with prednisolone.

Elkan AC, Engvall IL, Tengstrand B, Cederholm T, Hafström I. · Department of Rheumatology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. · Eur J Clin Nutr. · Pubmed #17637600 No free full text.

Abstract: OBJECTIVE: To evaluate diagnostic instruments for assessment of nutritional status in patients with rheumatoid arthritis (RA) in relation to objective body composition data. SUBJECTS AND METHODS: Study subjects include 60 in-ward patients (83% women, median age 65 years). Anthropometric measures and the nutritional tools Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening tool 2002 (NRS-2002). Body composition was determined by dual-energy X-ray absorptiometry and fat-free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated. RESULTS: Mean body mass index (BMI) for RA women and men were 24.4 and 26.9 kg/m(2), respectively. Twelve per cent of the women and none of the few men had BMI<18.5 kg/m(2), that is, the cutoff value for malnutrition. FFMI indicated 52% of the women and 30% of the men to be malnourished. The sensitivity and specificity for BMI to detect malnutrition according to FFMI were 27 and 100%, whereas for arm muscle circumference the sensitivity was 36% and the specificity 89% and for triceps skin fold 43 and 93%, respectively. For MNA, sensitivity was 85% and specificity 39% and for SGA 46 and 82%. Both MUST and NRS-2002 had sensitivity of 45% and specificity of 19%. CONCLUSION: A large proportion of in-ward RA patients had reduced FFMI. Concurrent elevation of fat mass made BMI a non-reliable tool to detect malnutrition. Of the tested clinical evaluation tools, MNA might be used as a screening instrument, but because of its low specificity it should be followed by body composition determination.

Ernestam S, Hafström I, Werner S, Carlström K, Tengstrand B. · Department of Rheumatology, Division of Clinical Chemistry, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · J Rheumatol. · Pubmed #17477470 No free full text.

Abstract: OBJECTIVE: To determine if major reduction of inflammation with longterm tumor necrosis factor (TNF) antagonist treatment has any influence on the adrenal and gonadal axes in patients with rheumatoid arthritis (RA). METHODS: Forty-eight patients with RA were treated with infliximab or etanercept for 2 years. Disease activity, clinical response, and physical function were evaluated and serum levels of high sensitivity C-reactive protein and interleukin 6 were analyzed before start of treatment and after 1 and 2 years. At the same timepoints adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) were analyzed; luteinizing hormone (LH), estradiol, and testosterone were analyzed as well in 18 male patients. RESULTS: DHEAS increased (p <or= 0.05) after 1 and 2 years of treatment with TNF antagonists. No change in serum levels of ACTH, cortisol, LH, estradiol, or testosterone was recorded during the 2 years. The increased levels of DHEAS correlated with improved physical function measured by Health Assessment Questionnaire (p <or= 0.01). There was no correlation between hormone levels and clinical response or inflammatory markers. A longitudinal stability in individual hormone levels was found between baseline and 2 years, most markedly for DHEAS levels (rs = 0.90, p <or= 0.01). A female subgroup characterized by low levels of DHEAS had a lower age at disease onset. CONCLUSION: The increased DHEAS levels may indicate an improved adrenal function during 2 years' treatment with TNF antagonists. Improved physical function, correlated to increased DHEAS levels, may be an effect of better adrenal function during powerful antiinflammatory treatment. The stability in individual hormone levels suggests a stable hormonal homeostasis, independent of inflammatory activity.

Forslind K, Hafström I, Ahlmén M, Svensson B, Anonymous00814. · Section of Rheumatology, Helsingborgs Lasarett, Helsingborg, Sweden. · Ann Rheum Dis. · Pubmed #17158139 No free full text.

Abstract: BACKGROUND: The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis. METHODS: 698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis. RESULTS: After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids. CONCLUSIONS: Early remission of rheumatoid arthritis by 28-joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.

Tengstrand B, Ernestam S, Engvall IL, Rydvald Y, Hafström I. · Reumatologiska kliniken, Karolinska Universitetssjukhuset Huddinge, SE-141 86 Stockholm, Sweden. · Lakartidningen. · Pubmed #16408702 No free full text.

Abstract: TNF-blockade has been increasingly used in the treatment of rheumatoid arthritis (RA). However, the safety is unclear and an increased risk of both tuberculosis and other infections has been identified. Recently severe fibrosing alveolitis has also been reported in RA-patients treated with TNF-blockade. We report a further six RA patients, who during treatment with infliximab or etanercept developed fulminant lung fibrosis with alveolitis. For four of the patients, the fibrosing alveolitis was fatal. All patients were RF positive and above 60 years and five had mild fibrosis associated with RA before TNF-blockade treatment. Duration of TNF-blockade treatment was for three patients only two months and for the other three, 20-51 months. Age above 60 years and previous lung fibrosis appear to be risk factors for developing fibrosing alveolitis in RA patients treated with TNF-blockade.

Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I. · University of Lund, Lund, Sweden. · Arthritis Rheum. · Pubmed #16255010 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA). METHODS: At the start of their initial treatment with a disease-modifying antirheumatic drug (DMARD), patients with early (duration < or =1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of <2.6. Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years. RESULTS: Of the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P = 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0-2] versus 1.25 [IQR 0-3.25]; P = 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no-prednisolone group (P = 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no-prednisolone group (P = 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2-year study was similar in the 2 treatment groups. CONCLUSION: Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA.

Forslind K, Ahlmén M, Eberhardt K, Hafström I, Svensson B, Anonymous00310. · Section of Rheumatology, Helsingborgs Iasarett, Helsingborg, Sweden. · Ann Rheum Dis. · Pubmed #15308518 links to  free full text

Abstract: OBJECTIVE: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. METHODS: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. RESULTS: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. CONCLUSIONS: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.

Tengstrand B, Ahlmén M, Hafström I. · Department of Rheumatology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden. · J Rheumatol. · Pubmed #14760787 No free full text.

Abstract: OBJECTIVE: This prospective study analyzed influence of patient's sex on early rheumatoid arthritis (RA) within one year of disease onset and after 2 years' followup. METHODS: A total of 844 consecutive patients, 538 women, with RA of less than 12 months were studied. Standardized clinical and radiographic assessments were performed at study entry and after 2 years. The association of several variables at study entry with the outcome variables Disease Activity Score (DAS28), functional disability measured by the Health Assessment Questionnaire (HAQ), and, in 390 patients, Larsen score at the 2-year followup were analyzed in men and women separately. RESULTS: At study entry the women were younger compared with the men and the sexes showed different age distributions. The women had higher DAS28 and HAQ scores. However, women below 50 years of age at study entry had milder disease than older women and close to that of men. At 2-year followup the women still had higher DAS28 and HAQ scores compared to men, who had achieved remission in a higher frequency. Larsen score showed no sex difference either at study entry or after 2 years. Presence of rheumatoid factor (RF) was associated with lower age at study entry and higher DAS28 at followup in men only. Higher DAS28 and HAQ scores at entry were more strongly correlated with severe disease at followup in women than in men. Presence of the "shared epitope" was not associated with age or the outcome variables DAS28 and Larsen score in either sex. CONCLUSION: The disease phenotype in early RA was significantly different between men and women, particularly concerning age, disease activity, and functional capacity. There were differences between the sexes concerning early disease characteristics associated with outcome at 2 years of followup.

Forslind K, Keller C, Svensson B, Hafström I, Anonymous00342. · Rheumatology Section, Department of Medicine, Helsingborg's lasarett, Helsingborg, Sweden. · J Rheumatol. · Pubmed #14719199 No free full text.

Abstract: OBJECTIVE: Data suggest that reduced bone mass may be associated with radiological damage in rheumatoid arthritis (RA). We investigated if patients with reduced bone mineral density (BMD) at onset of RA had more radiological damage at onset and after 2 years than patients with normal BMD. METHODS: BMD at lumbar spine and hip was measured in 204 patients with recent RA at presentation. At baseline and after 2 years, radiographs of hands and forefeet were evaluated according to the Larsen method. At the same time-points, Disease Activity Score (DAS 28) and functional disability (the Stanford Health Assessment Questionnaire, HAQ) were assessed. RESULTS: The 134 women and 70 men had a mean age of 55 and 61 years, respectively. Reduced bone mass (RBM, Z score < or = 1.0 SD) in at least one site was found in 46.0% of women and 62.5% of men. T and Z scores correlated significantly with Larsen scores both at baseline and after 2 years for the total patient cohort. Calculated separately for the sexes, significant correlations were found only for women. Women but not men with reduced bone mass and osteoporosis had higher Larsen scores at baseline and after 2 years than those without. From a stepwise multiple logistic regression analysis Z score trochanter and baseline C-reactive protein were selected as independent predictors of joint damage, measured as proportion over the median Larsen scores. This model could explain about 25% of the "variance" in outcome (Nagelkerke R2 = 0.27). CONCLUSION: Reduced BMD at onset of RA in women was associated with a higher Larsen score at baseline and after 2 years, indicating that the development of reduced bone mass and joint destruction in RA may have a common pathophysiological mechanism.

Tengstrand B, Carlström K, Felländer-Tsai L, Hafström I. · Department of Rheumatology, R92, Huddinge University Hospital, 141 86 Stockholm, Sweden. · J Rheumatol. · Pubmed #14677174 No free full text.

Abstract: OBJECTIVE: Men with rheumatoid arthritis (RA) have a higher than normal frequency of low testosterone levels, but not much is known about other sex hormones. We investigated serum levels of estradiol, estrone, and the adrenal androgen dehydroepiandrosterone (DHEAS) in men with RA and evaluated the association of various disease variables with these sex hormones. METHODS: Inflammatory activity, measured as disease activity score including 28 joints (Disease Activity Score 28), and degree of disability, measured with the Health Assessment Questionnaire, were estimated in 101 men with RA. Presence of erosions, rheumatoid factor (RF), smoking habits, and body mass index were recorded. DHEAS (not measured in patients taking glucocorticoids), estradiol, and estrone were measured in patients and in healthy controls. RESULTS: DHEAS and estrone concentrations were lower and estradiol was higher in patients compared with healthy controls. DHEAS differed between RF positive and RF negative patients. Estrone did not correlate with any disease variable, whereas estradiol correlated strongly and positively with all measured indices of inflammation. CONCLUSION: Men with RA had aberrations in all sex hormones analyzed, although only estradiol consistently correlated with inflammation. The high levels of estradiol may have positive implications for bone health. The low levels of estrone and DHEAS may depend on a shift in the adrenal steroidogenesis towards the glucocorticoid pathway, whereas increased conversion of estrone to estradiol seemed to be the cause of the high estradiol levels.

Tengstrand B, Hafström I. · Department of Rheumatology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden. · J Rheumatol. · Pubmed #12415584 No free full text.

Abstract: OBJECTIVE: To quantify bone mineral density (BMD) in men with rheumatoid arthritis (RA) and to evaluate the influence of various disease-specific and non-disease-specific variables on bone mass. METHODS: Dual energy x-ray absorptiometry was performed in 104 male patients with RA and BMD was measured in lumbar spine, femoral neck, trochanter, and Ward's triangle. Inflammatory activity, measured as Disease Activity Score including 28 joints (DAS28), degree of functional impairment measured with the Health Assessment Questionnaire, and sex hormones (bioavailable testosterone, DHEAS, estradiol, and estrone) were estimated. Presence of erosions, rheumatoid factor, and current treatment as well as body mass index and smoking habits were recorded. Correlations were performed with nonparametric tests and multiple regression analyses. RESULTS: BMD was reduced in both spine and hip compared to an age matched reference population. Erosive disease was the variable with the strongest correlation with BMD. Treatment with sulfasalazine correlated positively with BMD at 3 of the 5 measured bone sites. However, in multivariate analysis significance was sustained only in the trochanter region. There were no correlations between the degree of inflammation, levels of sex hormones, treatment with corticosteroids, or smoking and BMD at any site measured. CONCLUSION: A large proportion of the men with RA had reduced bone mass. Sex hormone levels and treatment with corticosteroid did not influence BMD, nor did current degree of disease activity. Erosive disease was closely correlated with low BMD, whereas sulfasalazine was associated with high BMD at least in the trochanter region.

Tengstrand B, Carlström K, Hafström I. · Department of Rheumatology, Karolinska Institutet at Huddinge University Hospital, 141 86 Stockholm, Sweden. · Rheumatology (Oxford). · Pubmed #11934965 links to  free full text

Abstract: OBJECTIVES: To study bioavailable testosterone (T) in men with rheumatoid arthritis (RA) by determining non-sex hormone-binding globulin (SHBG)-bound T (NST) under standardized conditions and to investigate if NST is related to disease variables. METHODS: Basal serum concentrations of total T, SHBG and luteinizing hormone (LH) were measured in 104 men with RA, and the levels of NST as well as the quotient T/SHBG were calculated. The data were compared with those of 99 age-matched healthy men. The results were analysed separately for the age groups 30-49, 50-59 and 60-69 yr. RESULTS: The RA men had lower NST levels than the healthy men in all age groups. T levels and the T/SHBG ratio were lower only in the age group 50-59 yr. SHBG did not differ significantly. LH was significantly lower in the patients than in the controls. Thirty-three of the 104 patients were considered to have hypogonadism compared with seven of the 99 healthy men. The only clinical variable apart from age that had a significant impact on NST was the Stanford Health Assessment Questionnaire (HAQ). CONCLUSION: Men with RA had lower levels of bioavailable T and a large proportion were considered hypogonadal. The low levels of LH suggested a central origin of the relative hypoandrogenicity.

Keller C, Hafström I, Svensson B, Anonymous00259. · Department of Medicine, Helsingborgs lasarett, Sweden. · Scand J Rheumatol. · Pubmed #11578016 No free full text.

Abstract: OBJECTIVE: To study bone mineral density (BMD) in patients with early rheumatoid arthritis. METHODS: Dual x-ray absorptiometry was performed in 227 patients, 149 women and 78 men, with rheumatoid arthritis (RA) of no more than 12 months duration. RESULTS: Women, as well as men above 60 years of age, had a BMD at spine and hip comparable with age and sex matched reference populations. Men younger than 60 years had a tendency to lower BMD. Although the proportion of female patients with osteoporosis was not higher than in the reference, population the proportion of patients with reduced bone mass was increased, and this was found also in men. There was no significant association between BMD and disease duration, disease activity or disability. CONCLUSION: Untreated patients with early RA have a BMD in spine and hip not significantly different from that of normal reference populations. However, an increased number of the patients had reduced bone mass already at disease onset.