Rheumatoid Arthritis: Jacobs JW

Verstappen SM, Jacobs JW, Hyrich KL. · No affiliation provided · J Rheumatol. · Pubmed #17985411 links to  free full text

This publication has no abstract.

van der Zant FM, Boer RO, Moolenburgh JD, Jahangier ZN, Bijlsma JW, Jacobs JW. · Department of Nuclear Medicine, Hospital Medical Center Alkmaar, The Netherlands. · Clin Exp Rheumatol. · Pubmed #19327243 No free full text.

Abstract: OBJECTIVE: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO). METHODS: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4. RESULTS: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03. CONCLUSION: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.

Bakker MF, Jacobs JW, Verstappen SM, Bijlsma JW. · University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, F02.127, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #17934098 No free full text.

Abstract: OBJECTIVE: To evaluate the available evidence on the efficacy and feasibility of the new concept of tight control in randomised trials in patients with rheumatoid arthritis (RA). Tight control is a treatment strategy tailored to the individual patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. METHODS: The literature database PubMed was searched and yielded four trials: the FIN-RACo trial, the TICORA study, the BeSt study and the CAMERA study. RESULTS: Tight control resulted in greater improvement and a higher percentage of patients meeting the preset aim of low disease activity or remission when compared to the control intervention. In the FIN-RACo trial, analysing the subset of patients completing the study, 68% in the tight control group achieved remission (DAS28<2.6) verus 41% in the contrast group [corrected] In the TICORA study, 65% of patients in the tight control group versus 16% of the contrast group achieved remission, based on DAS<1.6 (p<0.0001). In the CAMERA study, 50% of patients in the tight control group using a computer decision model achieved remission, versus 37% in the contrast group (p = 0.029). The BeSt study consisted of only tight control groups aimed at a DAS<1.6; remission was achieved in 38-46% of patients. This is higher than the range of remission in earlier trials of 13-36%. CONCLUSION: Tight control aiming for low disease activity or even better still, remission, seems a promising option in treating patients with RA in clinical trials and probably also in daily practice.

Sharp JT, van der Heijde D, Angwin J, Duryea J, Moens HJ, Jacobs JW, Maillefert JF, Strand CV, Anonymous00377. · University of Washington School of Medicine, Seattle, WA, USA. · J Rheumatol. · Pubmed #16331786 No free full text.

Abstract: Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis. We review methods for measuring joint space width in finger, toe, and wrist joints; special attention is given to how the joint edges are found, the method used to measure distance between joint margins, size of an area of the sampled joint, and reproducibility of measurements. Methods for measurement of erosion size, which have had less attention, are briefly discussed.

Jacobs JW, van Vugt RM, Swen WA. · Universitair Medisch Centrum Utrecht, afd. Reumatologie en Klinische Immunologie, F02.127, Postbus 85.500, 3508 GA Utrecht. · Ned Tijdschr Geneeskd. · Pubmed #16114288 No free full text.

Abstract: Musculoskeletal ultrasonography of the rheumatologist can be useful as a supplement to physical diagnostic assessment or as an aid to diagnostic puncture or therapeutic injection. The essence of musculoskeletal ultrasonography includes visualisation of joints and periarticular structures, muscles, tendons, tendon-sheets and insertions. With ultrasound, punctures, biopsies, and injections can be performed more precisely. A specific ultrasound technique is (color and power) doppler; three-dimensional ultrasonography is a promising new imaging modality. The learning curve of musculoskeletal ultrasonography differs according to indication. Data regarding the validity, reproducibility, sensivity and specificity of ultrasonographic findings are scarce. Further development of guidelines for the use and indications of musculoskeletal ultrasonography is warranted.

Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW. · Reumatologia, Hospitais da Universidade, 3000-075 Coimbra, Portugal. · Ann Rheum Dis. · Pubmed #16107513 links to  free full text

Abstract: Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.

Masi AT, Aldag JC, Jacobs JW. · Department of Medicine, University of Illinois College of Medicine at Peoria, One Illini Drive, PO Box 1649, Peoria, IL 61656, USA. · Rheum Dis Clin North Am. · Pubmed #15639060 No free full text.

Abstract: Current concepts of neuroendocrine immune (NEI) aspects of rheumatoid arthritis (RA) are reviewed and recent clinical trials of glucocorticoids and sex steroids are summarized. A novel physiopathogenetic perspective is presented. Data are provided of amplified NEI interactions and dysregulation, many years before symptomatic onset of RA. Chronic imbalances between the NEI, vascular endothelial, neural, and other vital counterregulatory intertwined networks are proposed to cause RA and influence its disease activity. Future research may reveal means of diminishing the onset risk as well as disease activity of RA by controlling these imbalances of NEI and other vital networks.

Verstappen SM, Bijlsma JW, Verkleij H, Buskens E, Blaauw AA, ter Borg EJ, Jacobs JW, Anonymous00105. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #15188338 links to  free full text

This publication has no abstract.

Bijlsma JW, Van Everdingen AA, Huisman M, De Nijs RN, Jacobs JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. · Ann N Y Acad Sci. · Pubmed #12114262 No free full text.

Abstract: Recently, four prospective placebo-controlled studies have further evaluated the disease-modifying properties of glucocorticoids in the treatment of rheumatoid arthritis. These studies irrefutably show that the use of (low) doses of glucocorticoids leads to a significant retardation of the progression of erosions, especially in early rheumatoid arthritis. This effect on erosions seems more impressive and probably more persistent than the well-known relief during low-dose glucocorticoid therapy of symptoms, such as pain, stiffness, and joint scores. The management of the (side) effects of glucocorticoids on bone has clearly improved in the last years. These two developments lead to a further optimizing of glucocorticoid treatment in patients with rheumatoid arthritis.

Bijlsma JW, Jacobs JW. · Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands. · Rheum Dis Clin North Am. · Pubmed #11084950 No free full text.

Abstract: Bone loss is a hallmark of RA. Factors influencing generalized bone loss include RA-specific factors such as the influence of disease activity and deficient sex hormone status and more general mechanisms (e.g., due to the use of glucocorticoids). Reducing disease activity has a positive effect on bone. Estrogens or androgens can restore deficiency of the sex hormones with a small positive effect on BMD. The more pronounced bone loss occurs when RA patients are being treated with glucocorticoids. This bone loss can be reduced by the concomitant use of calcium and vitamin D and, in most patients, by the use of bisphosphonates as well.

Jacobs JW, Blaauw AA, Dijkmans BA, van Riel PL, Bijlsma JW. · Universitair Medisch Centrum, afd. Reumatologie en Klinische Immunologie, Utrecht. · Ned Tijdschr Geneeskd. · Pubmed #10682647 No free full text.

Abstract: As soon as the diagnosis 'early rheumatoid arthritis (RA)' is made, a disease-modifying antirheumatic drug (DMARD) should be prescribed without delay. Methotrexate in dosages up to 30 mg once weekly is being used more frequently than in the past, also in early RA. Combination therapy with DMARDs is indicated in case of insufficient effect of a single DMARD. Combinations with methotrexate appear to be especially effective, like methotrexate and cyclosporin. A novel effective DMARD is leflunomide. In the near future promising biologicals will probably be applied in clinical daily practice, presumably in combination with conventional DMARDs. New non-steroidal anti-inflammatory drugs (NSAIDs) have been developed that are probably safer than conventional NSAIDs. If the recent finding that glucocorticoids are able to inhibit joint damage in (early) RA will be confirmed, prednisone might be used more often in (early) RA. Bone marrow transplantation in RA is still experimental.

Verstappen SM, van Albada-Kuipers GA, Bijlsma JW, Blaauw AA, Schenk Y, Haanen HC, Jacobs JW, Anonymous00039. · University Medical Centre Utrecht, Department of Rheumatology and Clinical Immunology, PO Box 85500, 3508 GA Utrecht, Netherlands. · Ann Rheum Dis. · Pubmed #15130899 links to  free full text

Abstract: OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.

van Everdingen AA, Siewertsz van Reesema DR, Jacobs JW, Bijlsma JW. · University Medical Center, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #15077265 links to  free full text

Abstract: OBJECTIVE: Our previous analysis of patients with early active rheumatoid arthritis (RA) treated with prednisone or placebo revealed the following discrepancy: although a significant retardation of joint damage was observed in the prednisone group compared with the placebo group, no differences in clinical variables between the 2 groups were observed, due to greater use of additional therapy in the placebo group. We sought to investigate whether this discrepancy would extend to variables of well-being. METHODS: We conducted a double-blind, randomized, placebo-controlled clinical trial of prednisone (10 mg) in patients with RA; the duration of the study was 2 years. Following the placebo-controlled trial, a 1-year open-label followup study was conducted in 81 patients with early (</=1 year) active, previously untreated RA. Forty-one patients were allocated to receive oral prednisone, 10 mg/day, and 40 patients were assigned to the placebo group. Analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), local injections of a glucocorticoid (only when absolutely necessary), and use of physiotherapy were allowed in both groups. After 6 months, sulfasalazine (2 gm/day) could be prescribed as rescue therapy in both groups. At the beginning of the study and every 6 months thereafter, 2 questionnaires (the VDF [Dutch version of the Health Assessment Questionnaire] and the IRGL [Dutch version of the Arthritis Impact Measurement Scales]) were administered. A visual analog scale (VAS) for morning pain was administered every 3 months. Disease activity and radiologic scores were assessed. RESULTS: VDF scores in the 2 groups were not statistically significantly different. No statistically significant differences between groups were observed in almost all parameters of the IRGL. In the prednisone group (and only at 6 months), the VAS scores for morning pain and general well-being showed improvement comparable with the transient improvement in some of the disease activity variables. In the prednisone group, use of NSAIDs, analgesics, local injections of glucocorticoids, and physiotherapy sessions was approximately 50% that in the placebo group. CONCLUSION: Although significant retardation of joint damage in the prednisone group indicates better disease control, no differences between the groups for variables of well-being were found. This discrepancy may be attributed to greater use of additional therapy in the placebo group. In future clinical trials, the use of additional therapies should be taken into account when analyzing the differences in effect between drugs.

Verstappen SM, Jacobs JW, Bijlsma JW, Anonymous00220. · University Medical Center Utrecht, Department of Rheumatology and Clinical Immunology, F02.127, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. · Clin Exp Rheumatol. · Pubmed #14969070 No free full text.

Abstract: Since 1990 the Utrecht Rheumatoid Arthritis Cohort study group has performed several clinical trials on different treatment strategies in early rheumatoid arthritis (RA) patients. From 1990 till 1994, patients were randomly assigned to the pyramid strategy group or the early DMARD group. Patients in the early DMARD group were allocated to one of the three following treatment strategies: strategy I, starting with hydroxychloroquine (HCQ); strategy II, starting with intramuscular gold (iAU); or strategy III, starting with oral methotrexate (MTX). After one year, statistically significant advantages for the early DMARD group compared with the pyramid group were found for disability, pain, joint score, and ESR. The increase in radiological damage did not differ significantly between the two strategy groups. These first year results proved that early introduction of DMARDs is more beneficial than a delayed introduction. After 5 years, however, no prolongation of the clinical advantages in favor of the early DMARD group, as observed after one year, was found. It was found that patients assigned to the pyramid group received more intra-articular injections during the first two years; at the end of this period 75% of them used DMARDs, especially the more aggressive DMARDs. Based on the first year results, all patients were randomly assigned to one of the three treatment strategies in the early DMARD group between 1994 and 1998. Patients who started with MTX or iAU as the first DMARD demonstrated better results regarding clinical efficacy and radiological damage after 2 years. However, more patients who received iAU therapy had to discontinue their therapy compared with patients who took MTX. We therefore conclude that MTX is the DMARD of first choice and that treatment should be tailored to the individual patient.

Verstappen SM, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, Borg EJ, Hofman DM, van der Veen MJ, Anonymous00035. · University Medical Center Utrecht, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #12847672 links to  free full text

Abstract: OBJECTIVE: To evaluate whether the clinical advantages observed after 1 year in a randomized controlled clinical trial, in which 2 treatment strategies were compared (the early disease-modifying antirheumatic drug [DMARD] approach versus the pyramid approach), persist after 5 years. METHODS: In this study, 238 patients with recently diagnosed rheumatoid arthritis (RA) were randomized to either the pyramid group (n = 56) or the early DMARD group (n = 182). Patients assigned to the pyramid group received nonsteroidal antiinflammatory drugs for at least 1 year after inclusion (the mean +/- SD lag time until first prescription of a DMARD was 14 +/- 9 months). Patients in the early DMARD group were treated with a DMARD immediately after inclusion. RESULTS: After 5 years, data were available for 44 patients in the pyramid group (79%) and 145 patients in the early DMARD group (80%). No prolongation of the clinical advantages in favor of the early DMARD group, as observed after the first year, was demonstrated. Nevertheless, a significantly shorter delay time until complete response and a higher number of patients with overall clinically relevant improvement at several assessment points were observed in the early DMARD group compared with the pyramid group. CONCLUSION: The clinical results in favor of the early DMARD group, as observed after the first year, were not as evident after 5 years. This indicates that a more aggressive treatment approach in early RA is required, and that treatment should be continued for a prolonged period of time, in order to maintain the advantages obtained in the first year.

Huisman AM, Siewertsz van Everdingen AA, Wenting MJ, Lafeber F, van Reesema DR, Jacobs JW, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, PO Box 85000, 3508 GA Utrecht, The Netherlands. · Clin Exp Rheumatol. · Pubmed #12747278 No free full text.

Abstract: OBJECTIVE: Low or medium dose prednisone in early rheumatoid arthritis (RA), albeit with significant variation in clinical efficacy, reduces the progression of joint damage. The glucocorticoid receptor (GR) number in peripheral mononuclear cells (PBMC) might be helpful to predict which patients will respond to low or medium dose prednisone and therefore do not or will not need higher doses. With this in mind we determined in a double blind, placebo controlled study at baseline and yearly the GR number in PBMC. METHODS: Eighty-one early RA patients (disease duration less than one year) were included. All patients fulfilled the ACR criteria and were disease modifying antirheumatic drugs (DMARD) and glucocorticoid-naive. They were randomly assigned to treatment with 10 mg prednisone daily or placebo. From all patients disease activity (CRP, number of tender and swollen joints), the radiological joint score, bone mineral density, and the GR number in PBMC were measured annually. RESULTS: In females the GR number was up-regulated over time in both the prednisone and the placebo group. The same trend was observed in males. No correlations were found between the GR number in the prednisone users at the start of their treatment and changes in radiological scores or bone density after 2 years of treatment. No correlations were found between the GR number at the start and the clinical characteristics after a follow-up of 2 years. CONCLUSION: The GR number in the PBMC of early RA patients did not predict which patients would be prednisone responders based on clinical or radiological parameters. However, the up-regulation of the GR number in PBMC in early RA patients towards the GR number of healthy subjects during the first two years of their disease course seems to reflect a recovery or compensatory mechanism as a response to an ongoing inflammatory process. This recovery may be not enough to efficiently control the inflammatory situation.

van Everdingen AA, Siewertsz van Reesema DR, Jacobs JW, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands. · Clin Exp Rheumatol. · Pubmed #12747268 No free full text.

Abstract: OBJECTIVE: To investigate the incidence of osteoporotic fractures and effects on bone of low-dose glucocorticoid (GC) monotherapy in a group of previously untreated patients with early active RA we performed a double blind, randomised, placebo-controlled clinical trial. The study duration was 2 years, with an open follow-up during the third year. Patients were randomly allocated to receive 10 mg prednisone or placebo. METHODS: Non-steroidal anti-inflammatory drugs (NSAIDs) were allowed in both groups. After 6 months sulphasalazine (2 gr daily) could be prescribed as rescue therapy in both groups. Except for 500 mg calcium supplement daily, no specific preventive measures were taken. This was a normal procedure at the time the study was designed (1989-1991). At the start of the study and every 6 months, X-rays of the twelfth thoracic and of all lumbar vertebrae were scored using the Kleerekoper method, and every year biochemical parameters of bone metabolism and bone mineral density (BMD, expressed in T-scores) and bone mineral content (BMC, expressed in g/cm) were assessed. RESULTS: In the prednisone group there was a higher incidence during the study of lumbar vertebral fractures than in the placebo group: 7 vs 4 respectively. This difference did not reach statistical significance however, probably because of the small numbers. One patient of the prednisone group suffered an osteoporotic fracture of the pelvis. In the 2-year study and the subsequent follow-up year, no other peripheral fractures were seen in either group. No significant changes from baseline in BMD and BMC of the hips were seen in either group during the study and the follow-up year. In the lumbar spine, BMD in the prednisone group decreased although not statistically significantly during the whole study. No correlation between changes in serum osteocalcin and BMD was observed. CONCLUSION: Low-dose prednisone monotherapy for patients with early active previously untreated RA seems to increase the risk of fractures not only by reducing the BMD but also by changes in bone strength and structure.

van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. · Department of Rheumatology, Deventer Hospital, Box 5001, 7400 GC Deventer, the Netherlands. · Ann Intern Med. · Pubmed #11777359 links to  free full text

Abstract: BACKGROUND: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis. OBJECTIVE: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis. DESIGN: 2-year randomized, double-blind, placebo-controlled clinical trial. SETTING: 2 outpatient rheumatology clinics. PATIENTS: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs. INTERVENTION: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication. MEASUREMENTS: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months. RESULTS: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group. CONCLUSIONS: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

de Nijs RN, Jacobs JW, Bijlsma JW, Lems WF, Laan RF, Houben HH, ter Borg EJ, Huisman AM, Bruyn GA, van Oijen PL, Westgeest AA, Algra A, Hofman DM, Anonymous00207. · Department of Rheumatology and Clinical Immunology, F02.127, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #11752508 links to  free full text

Abstract: OBJECTIVE: This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. PATIENTS AND METHODS: This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. RESULTS: Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). CONCLUSION: There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.

van Jaarsveld CH, Jahangier ZN, Jacobs JW, Blaauw AA, van Albada-Kuipers GA, ter Borg EJ, Brus HL, Schenk Y, van Der Veen MJ, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center, PO Box 85500, 3508 GA Utrecht, the Netherlands. · Rheumatology (Oxford). · Pubmed #11136881 links to  free full text

Abstract: OBJECTIVE: To evaluate the toxicity of slow-acting anti-rheumatic drugs (SAARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) in early rheumatoid arthritis. METHODS: Patients were randomized to receive a SAARD-hydroxychloroquine (HCQ; n=120), i.m. gold (n=114) or methotrexate (MTX; n=118)-or a NSAID only (n=67). Patients in the three SAARD groups were allowed to take NSAIDs. Follow-up included 545 patient-years (p-yr). Adverse effects were attributed to specific medications using the Naranjo scoring method. RESULTS: Fifty-five per cent of the patients suffered from adverse effect(s). Adverse effects were most common during i.m. gold therapy (87 per 100 p-yr), which led to permanent discontinuation of this treatment in 31 cases. The incidences of adverse effects that were probably attributable to NSAIDs in patients treated simultaneously with a SAARD were similar for the three SAARD groups. The mean period until the first adverse effect was longer in the MTX group (39 weeks) than in the HCQ group (27 weeks). Baseline clinical and sociodemographic parameters were not predictive of the occurrence of adverse effects. CONCLUSION: No adverse effect could be classified as definitely related to either SAARDs or NSAIDs by the Naranjo scoring method. The incidence of possible adverse effects of NSAIDs and SAARDs was 72 per 100 p-yr, and adverse effects led to permanent discontinuation of the therapy in 56 cases (13%) (31 patients receiving i.m. gold, 12 receiving MTX, 10 receiving HCQ and three receiving NSAID only).

Jacobs JW, Geenen R, Evers AW, van Jaarsveld CH, Kraaimaat FW, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #11114284 links to  free full text

Abstract: OBJECTIVE: To investigate the short term effects of corticosteroid pulse treatment (CPT) on disease activity, functional ability, and psychological wellbeing of patients with active rheumatoid arthritis (RA). METHODS: Of 66 consecutive patients with active RA admitted for CPT, erythrocyte sedimentation rate, C reactive protein level, haemoglobin concentration, platelet count, duration of early morning stiffness, a joint score, and grip strength were assessed before and after CPT. Additionally, a health status questionnaire was administered. Effects of CPT were expressed as before to after intervention effect sizes and, to place them in perspective, compared with the (long term) effect sizes of disease modifying antirheumatic drug (DMARD) treatment in a historical contrast group of patients with early RA. RESULTS: Statistically significant improvement from baseline in disease activity, physical functioning, and psychological wellbeing after CPT was seen, with moderate to large effect sizes, resembling the effects seen after DMARD treatment. Neither depression nor psychosis occurred during and after CPT. CONCLUSION: Qualitatively and quantitatively the short term effects of CPT in patients with active established RA on various dimensions of health status resemble the long term effects of conventional DMARD treatment in patients with early RA. Psychological disorders do not seem to be common short term side effects of CPT in patients with active RA.

van Jaarsveld CH, Jacobs JW, van der Veen MJ, Blaauw AA, Kruize AA, Hofman DM, Brus HL, van Albada-Kuipers GA, Heurkens AH, ter Borg EJ, Haanen HC, van Booma-Frankfort C, Schenk Y, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Centre, Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #10834865 links to  free full text

Abstract: OBJECTIVES: To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect. METHODS: Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up. RESULTS: All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies. CONCLUSION: Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity.

van Jaarsveld CH, ter Borg EJ, Jacobs JW, Schellekens GA, Gmelig-Meyling FH, van Booma-Frankfort C, de Jong BA, van Venrooij WJ, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands. · Clin Exp Rheumatol. · Pubmed #10609067 No free full text.

Abstract: OBJECTIVE: To study the prognostic value of the antiperinuclear factor (APF), determined by an indirect immunofluorescence test (IIF) and a recently developed anti-citrullinated cyclic peptide (CCP) ELISA, in combination with rheumatoid factor (RF) status, in early RA (< 1 year). METHODS: A total of 249 participants in a randomized trial of treatment strategies were divided into 4 groups according to their APF (or CCP) and RF status at baseline. Differences in disability, joint involvement and radiological damage over a 3-year period were analysed. RESULTS: APF-IIF results differed from CCP-ELISA in 42 cases (17%); 38 of the 42 had a positive IIF and negative ELISA value. Disability after 3 years did not differ significantly between the RF and APF groups. APF- patients had significantly lower Thompson joint scores compared to APF+ patients (6 vs 24 for CCP-ELISA; 2 vs 24 for IIF). RF+APF+ patients exhibited more radiological damage compared to RF-APF- patients. RF+APF- and RF-APF+ patients had intermediate scores. Within the RF+ and RF- groups, APF+ was associated with more radiological damage and thus yielded prognostic information in addition to RF. In this respect, the results of ELISA and IIF were comparable. Thirty percent of the RF+APF+ patients had a radiological score higher than 45, compared to 13% of the RF+APF-, none of the RF-APF+, and 2% of RF-APF- patients (p < 0.001). In addition, more large joints were affected in APF+ than in APF- patients, while no difference was observed between RF+ and RF- patients. CONCLUSION: APF has prognostic value in addition to RF for joint involvement and radiological damage in early RA. The CCP-ELISA technique for APF assessment may facilitate its use in clinical practice. However, the prognostic value of the two tests lies in their ability to predict mild disease. Reliable identification at baseline of individual patients with progressive disease is still not possible.

Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW, Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T, Anonymous00057. · Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, and Medcare Oy, Hämeentie 1, 44100 Aänekoski, Finland. · Arthritis Res Ther. · Pubmed #19144159 links to  free full text

Abstract: ABSTRACT : INTRODUCTION : Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS : The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS : Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS : In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.

Jacobs JW, Bijlsma JW. · Universitair Medisch Centrum Utrecht, afd. Reumatologie en Klinische Immunologie, Utrecht. · Ned Tijdschr Geneeskd. · Pubmed #18265793 No free full text.

Abstract: In a recent study involving 691 patients, for whom general practitioners had ordered a rheumatoid factor test in 2004, the serum samples had simultaneously been analysed for antibodies against citrullinated fibrinogen. Two years later, 28 of 616 individuals of the original sample met the classification criteria for rheumatoid arthritis. In 8 of these 28 patients (29%), the rheumatoid factor test had been positive in 2004 and the anti-citrullinated fibrinogen test in 7 (25%) of the 28. The pre-test probability for rheumatoid arthritis was thus 5% and the post-test probability in case of a positive test for anti-citrullinated fibrinogen antibodies 37%. The pre-test probability for not having rheumatoid arthritis was 95% and the post-test probability in case of a negative test for anti-citrullinated fibrinogen antibodies 96%. In a patient sample with a low probability or incidence of rheumatoid arthritis, screening with these tests only moderately increases the chance of having rheumatoid arthritis in case of a positive test and adds virtually nothing to exclude rheumatoid arthritis.