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SAT0143 THE EFFECT OF ALENDRONATE PLUS METHOTREXATE FOR A STRUCTURAL BENEFIT IN EARLY
RHEUMATOID ARTHRITIS. COMPARED TO METHOTREXATE ALONE
k. kume*1, k. amano1, s. yamada1, h. nagata1, k. amano2 1rheumatology, hiroshima clinic, 2rheumatology, sky clinic, hiroshima, Japan Background: Bisphosphonates, the most commonly therapeutic agents for osteoporosis prevention and treatment, hold
osteoarthritis treatment appeal based on their known pharmacology of altering bone remodel ing through a direct inhibitory effect on the osteoclast. But there is no evidence of bisphophonates about bone destruction in rheumatoid arthritis. Objectives: To compare the efficacy and safety of alendronate plus methotrexate (MTX) versus MTX monotherapy in
patients with early rheumatoid arthritis (RA) 2years' duration who had not previously received MTX treatment. Methods: This was a one-year, open label randomized control ed, clinical findings and X-ray reader-blinded trial. RA
patients were eligible if their disease duration was under 2 years and they had no prior treatment with MTX or bisphophonates. Forty nine patients were randomly assigned in 2 treatment groups: alendronate (35mg/week alendronate per oral) plus MTX, MTX alone. MTX dosages were rapidly escalated to 12 mg/week.Al the patients were not treated with steroids. Co-primary end points at year 1 were American Col ege of Rheumatology improvement and mean change from baseline in the modified total Sharp score(TSS) by blinded assessmenter. Results: t week 52, the bisphophonates plus MTX group showed statistical y significantly less radiographic change in
TSS (mean 3.2; 95% CI 1.2 to 5.4) than the MTX alone group (mean5.8; 95% CI 3.8 to 9.0; p<0.01). And at week 52 the median percentage of American Col ege of Rheumatology improvement (ACR-N) was not so significant difference with two groups (bisphophonates plus MTX 29.2%, MTX alone 28.4%, respectively; P=0.57). Adverse events were similar in
Conclusion: Combination therapy with alendronate plus MTX provides greater radiographic benefit than MTX alone, in
the treatment of early rheumatoid arthritis. References: Firth JC, Monkkonen J, Auriola S, Monkkonen H, Rogers MJ. The molecular mechanism of action of the
antiresorptive and anti nflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum 2001;44:2201–10.[CrossRef][Medline] Evans CH, Mears DC. Binding of the bone-seeking agent 99mTc-1-hydroxyethylidene-1,1-diphosphonic acid to cartilage and col agen in vitro and its stimulation by Er3+ and low pH. Calcif Tissue Int 1980;32:91–4.[CrossRef][Medline AB0497 EFFICACY OF INTRAARTICULAR INJECTIONS OF HIALURONIC ACID FOR TREATMENT OF KNEE
OSTEOARTHRITIS: COMPARISON TO COMBINED TREATMENT WITH CHONDROPROTECTIVE AGENTS AND
PHYSICAL THERAPY
1Clinical department III, Institute of Rheumatology, Belgrade, Serbia Background: Intraarticular injections of hialuronic acid used for treatment of knee osteoarthris are efficious for fast
achieved and longstanding reduce of pain, as wel as for improvement of patients functional ability. Objectives: To compare efficacy of intraarticular injections of hialuronic acid (ORTHOVISC®,) and combined use of
chondroprotective agent No-Dol®, (glucosamine sulfate and chondroitine sulfate) and physical therapeuthic procedures for knee osteoarthritis treatment in 6 months period. Methods: 45 of total 90 patients enrol ed in this study, received intraarticular injections of ORTHOVISC®, (3 injections in
total - 30mg) at the begining of fol ow up and 45 patients were treated with oral No-Dol®, and physical therapy at the same time. Patients in both groups were of similar demographic (age, gender, BMI) and clinical (disease duration, knee osteoarthritis characteristics, radiological classification-Kel gren-Lawrence) characteristics. Al patients were fol owed in 6 months period. For assessment of treatment efficacy were used visual-analog scales (VAS) for pain and functional ability, as wel as Likert numeric scale for joint movement range after 3 and 6 months of treatment in first group of patients and after 3 weeks of physical therapy as wel as 3 and 6 months during use of No-Dol®, in second group of patients. Results: Data were analyzed using T- test . Patients received ORTHOVISC®, showed significant reduce of pain after
third injection (p<0.001), maximal pain reduce after 3 months (p<0.0001) and significant reduce of pain was found after 6 months (p<0.0001). In patients from second group pain reduction was found after 3 weeks of physical teratment, without statisticaly significance with pain increasement after 3 and 6 months. Patients functional ability was significantly increased after 3 and 6 months of treatment (p<0.001) in first group of patients compared to second group with slight increase after 3 months of treatment, without statistical significance. Knee movement range was significantly better after 3 months of treatment in first group of patients (p<0.005), compared to second group where knee movement range was better after 3 months of treatment, without statistical significance. Treatment effects were present after 6 months of treatment in both patient groups. Treatment eficacy was significantly better in patients receiving ORTHOVISC®, after 3 and 6 months of Conclusion: Intraarticular treatment with hialuronic acid preparations of high moleular weight and high concentration, with
trade name ORTHOVISC®,, dosing regimen 1 injection weekly for 3 weeks showed significantly better efficacy compared to the combined treatment with chondroprotective agens and physical therapy. References: 1. Balazs E,Denlinger JL.Viscosupplementation:a new concept in the treatment of
osteoarthritis.J.Rheumatol.1993;20 suppl 39):3-8. 2. Lo GH,La Val ey M,McAlindon T,et al.Intra-articular hyaluronic acid in the treatment of the knee osteoarthritis. JAMA
FRI0397 STRUCTURAL EFFICACIES OF GLUCOSAMINE SULFATE AND CHONDROITIN SULFATE IN KNEE
OSTEOARTHRITIS: A META-ANALYSIS
Y. Lee*1, J. Woo1, S. Choi1, J. Ji1, G. Song1 1Rheumatology, Korea University Medical Center, Seoul, South Korea Background: : Previous several studies have demonstrated by joint space narrowing (JSN) analysis the possibility that
glucosamine sulfate and chondroitin sulfate modify the disease state, but their effects remain debatable. Objectives: The aim of this study was to assess the structural efficacies of daily glucosamine sulfate and chondroitin
sulfate in patients with knee osteoarthritis (OA). Methods: The authors surveyed randomized control ed studies that examined the effects of long-term daily glucosamine
sulfate and chondroitin sulfate on joint space narrowing (JSN) in knee OA patients using the Medline and the Cochrane Control ed Trials Register, and by performing manual searches. Meta-analysis was performed using a fixed effect model because no between-study heterogeneity was evident. Results: Six studies involving 1502 cases were included in this meta-analysis, which consisted of two studies on
glucosamine sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did not show a significant effect versus controls on minimum JSN over the first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429). However, after 3 years of treatment glucosamine sulfate revealed a smal to moderate protective effect on minimum JSN (SMD 0.432, 95% CI 0.235 to 0.628, P < 0.001). The same was observed for chondroitin sulfate, which had a smal but significant protective effect on minimum JSN after 2 years (SMD 0.261, 95% CI 0.131 to 0.392, P < 0.001).
Conclusion: This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological
progression of OA of the knee after daily administration for over 2 or 3 years. THU0334 AN EVIDENCE-BASED ASSESSMENT OF THE EFFICACY AND SAFETY OF GLUCOSAMINE SULFATE
AS A SYMPTOMATIC AGENT IN OSTEOARTHRITIS, STANDARDISED ACCORDING TO THE GRADE SYSTEM
A. Neuprez*1, L. C. Rovati2, G. Giacovel i2, B. Barbetta2, S. Scholtissen1
1Public Health, Epidemiology and Economics, University of Liege, Liege, Belgium, 2Clinical Pharmacology, Rottapharm, Background: Inconsistencies in the interpretation of glucosamine sulfate (GS) clinical trial results are present in the
Objectives: To col ect and review the clinical trial evidence of the efficacy and safety of GS as a symptomatic treatment
of osteoarthritis (OA) according to a standardised instrument, the GRADE system (1). Methods: Medline was searched for randomised control ed trials of GS and for recent, high-quality systematic reviews
and meta-analyses (SR/MA) of GS up to December 2007. A total of 22 RCTs were retrieved and classified for relevant information. Al were present in 3 SR/MA: -Vlad et al (A&R 2007) includes 12 placebo-control ed studies of any formulation of GS (and 3 of glucosamine HCl, that were excluded due to lack of efficacy in any RCT); - Reginster (A&R 2007) focuses on the 3 pivotal trials of prescription crystal ine glucosamine sulfate 1500 mg once-a-day; -Towheed et al (Cochrane Library 2005) adds 4 old or smal placebo-control ed and 3 NSAID-control ed studies. The former two SR/MA were used for the efficacy assessment on pain, WOMAC pain and WOMAC function, while the latter was used for the safety assessment on patients with adverse events (AEs) and withdrawals for AEs. According to GRADE, evidence profiles were constructed considering study design, quality, consistency and directness, to determine overal quality of the evidence and importance of the outcomes, along with the size of the effect reported. Results: There were no serious limitations in the RCTs used for the efficacy evaluation. Pain assessment in Vlad 2007
was "direct" evidence, but the "important inconsistency" represented by the high heterogeneity in study results decreased the overal quality to "moderate" for an effect size (ES) of 0.44 (95% CI: 0.18-0.70), that could be considered "important (but not critical)" due to the use of different pain evaluation methods in the RCTs. Inconsistency disappeared in Reginster 2007 that focussed only on pivotal regulatory trials of prescription GS resulting in "high" overal quality for the "critical y important" outcomes of WOMAC pain/function with ES of 0.27 (0.12-0.43) and 0.33 (0.17-0.48), respectively. The safety assessment in the more comprehensive and heterogeneous database developed from Towheed 2005, suggested no difference with placebo and better tolerance than with NSAIDs.
Conclusion: The present standardised and evidence-based GRADE assessment is offered to expert panels for use in
future practice guidelines in OA. It suggests that glucosamine sulfate is safe and provides a smal but consistent effect on pain and function in OA when used as the prescription product in once daily dosing. High inconsistency makes uncertain the benefit of other formulations/dosages. References: 1)Atkins D et al. BMJ 2004;328:1490-7
AB0555 ASSOCIATION RESTLESS LEGS SYNDROME AND FIBROMYALGIA: CONTROLLED STUDY OF 102
PATIENTS
A. Simon*1, C. Dufauret-Lombard1, C. Bonnet1, P. Vergne-Sal e1, P. Bertin1, R. Trèves1 1Service de Rhumatologie et Thérapeutique, CHRU Dupuytren, LIMOGES, France
Objectives: The main objective of the study was to compare the proportion of the restless legs syndrome (SJSR) in
fibromyalgic group versus patients suffering of others rheumatic diseases as control group. The secondary objective was to compare between theses groups the proportion of idiopathic SJSR and secondary SJSR and to estimate the severity of Methods: 102 patients were recruited in the service of rheumatology: 50 patients with fibromyalgia according to the ACR
criteria and 52 patients as control group. SJSR was diagnosed according to the International Restless Leg Syndrome Study Group criteria and severity of SJSR was estimated through the IRLSRS classification. Results: The results of the study show a significantly higher proportion of SJSR in the fibromyalgic group (28 %) compare
to the control group (11,5 %) (p < 0,05). The col ected data concerning the possibly secondary SJSR and the severity are not exploitable because of the limit of the sample size. We emit the physiopathological hypothesis that there is a possible intrication between a dopaminergic dysfunction in the SJSR and the fibromyalgia.
Conclusion: Our study shows an important proportion of SJSR in the fibromyalgic’s patients. So, these data imply that
dyssomnia should be considered in the treatment of the patients suffering from fibromyalgia. Nevertheless, a better understanding of the disturbances in the dopaminergic neuromediators in the fibromyalgia remains necessary 1Unidad de Reumatología, IPR. Hospital Universitario Gregorio Marañón, Madrid, 2Sección de Reumatología, Hospital Gral. Universitari d’Alacant, Alicante, 3Departamento de Psicología de la Personalidad, Evaluación y Tratamientos Background: Multiple domains should be considered in the evaluation of patients with fibromyalgia (FM). The most
frequent and severe clinical symptoms and comorbidities are very important parts of this syndrome and should be taken Objectives: To quantify the number and patient subjective importance of clinical symptoms and comorbidities for
establishing a rank with al those clinical manifestations that should be assessed in a priority manner in patients with FM. Methods: This is a multicentric, transversal study of a cohort of patients attended in specialized rheumatology clinics al
over the country (ICAF study). The frequency of the most common symptoms, active comorbidities (defined as wel defined diseases that are being treated at the time of patient inclusion), and the subjective importance given by the patient to these clinical manifestations in a Likert scale where 1 = no important, 2 = low important, 3 = moderate important and 4 The frequency of the symptoms or comorbidities was multiplied by the mean of importance given by the patients for Results: ICAF study cohort is composed of 301 patients (female 96,7%) distributed al over the country, with a mean age
of 48,73 ± 8,54 yr. and a mean evolution time of 11,51 ± 9,19 yr. The frequency of clinical manifestations, mean of importance, the product of both and the rank is shown in the table. Cognitive alterations (4th position), headaches (7th position), paresthesias (8th position) and dizziness (9th position) rank as more frequent and important than symptoms of depression. Among comorbidities, non inflammatory rheumatic diseases, upper GI disturbances, serum lipid alterations and hypertension rank higher. Clinical manifestations and comorbilities in patients with fibromyalgia Percentage
Importance
Sleep disorder
Cognitive alt.
Stiffness
Paresthesia
Dizziness
Depression
Sof tissue rheum.
Osteoarthritis
Upper GI disturb.
Serum lipid alt.
Hypertension
Discal herniation

Conclusion: Clinical manifestations such as cognitive alterations, headaches, paresthesias and dizziness are as frequent
and important as pain, fatigue, sleep disorders, stiffness, anxiety or depression. These clinical manifestations and the most frequent comorbidities should be also assessed in the clinical evaluation of FM patients together with the remaining outcome variables which are commonly used. SAT0450 PRODUCTION OF NITRIC OXIDE (NO) BY GRANULOCYTES IN FIBROMYALGIA
E. J. R. Souza*1, D. Caldeira Costa2, M. M. Chaves2, F. C. Lima e Silva3, J. A. Nogueira-Machado3 1Rheumatology, Hospital Santa Casa de Belo Horizonte, 2Biochemistry and Immunology, Universidade Federal de Minas Gerais, 3Núcleo de Pós-Graduação e Pesquisa, Hospital Santa Casa de Belo Horizonte, Belo Horizonte, Brazil Background: Fibromyalgia (FM) is a generalized chronic pain syndrome (1). Central sensitization contribute to or are
responsible for FM pain (2). Nitric oxide (NO) may play an important role. The NMDA activation induces calcium entry into the dorsal horn neurons (3), leading to the synthesis of NO (4). NO can enhance the release of sensory neuropeptides (substance P) contributing to the development of hyperalgesia and maintenance of central sensitization (5). Correlation between serum NO level and pain in FM patients were seen in a control ed study (6).
Objectives: Investigate the production of nitric oxide (NO) by granulocytes from patients with FM.

Methods: Twenty patients (ACR criteria), 18 women and 2 men, with ages ranging from 20 to 40 years (mean value 32.6
years) and sex- and age-matched healthy volunteers were selected. Al participants presented normal clinical and laboratory test evaluations. None of the FM group had used medications (except paracetamol) during the 2 week period prior to the commencement of the study. Granulocytes were purified from 10.0 mL samples of heparinised venous blood and incubated in a humidified atmosphere of CO2 for 16 h at 370C. The cel -free supernatants were col ected and nitrite concentration determined and the results were expressed as micromolar ( M) nitrite. Results: The production of NO (expressed in M nitrite) by granulocytes from FM patients was 24.5 times greater than

Conclusion: Results of the present study indicate that NO synthesis in granulocytes from FM patients is elevated. This
should encourage further researches, evaluating the potential role of NO in the pathophysiology of FM. References: 1. Yunus MB. Fibromyalgia syndrome: clinical features and spectrum. In: SR Pil emer, ed. The fibromyalgia
syndrome: current research and future directions in epidemiology, pathogenesis, and treatment. New York: Haworth 2. Clauw DJ, Chrousos GP. Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation 1997 (4):134–153. 3. Bennett GJ. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor J Pain 4. Mel er ST, Gebhart GF. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993 (52):127–136 5. Luo ZD, Cizkova D. The role of nitric oxide in nociception. Curr Rev Pain 2000 4:459–466. 6. Sendur OF, Turan Y, Tastaban E, Yenisey C, Serter M. Serum antioxidants and nitric oxide levels in fibromyalgia: a control ed study. Rheumatol Int 2008 (14). [Ep
FRI0166 SAFETY OF METHOTREXATE IN RHEUMATOID ARTHRITIS PATIENTS WITH INTERSTITIAL LUNG
DISEASE: A SYSTEMATIC LITERATURE RESEARCH
B. A. Cruz*1, F. A. Rocha2, R. M. Xavier3, G. R. C. Pinheiro4, D. C. Titton5, I. A. Pereira6 1Rheumatology, Biocor Instituto, Nova Lima, 2Rheumatology, Medical School, UFC, Fortaleza, 3Rheumatology, Medical School, UFRG, Porto Alegre, 4Rheumatology, Medical School, UERJ, Rio de Janeiro, 5Rheumatology, Medical School, UFPR, Curitiba, 6Rheumatology, Medical School, UFSC, Florianópolis, Brazil Background: Methotrexate (MTX) is the most prescribed disease modifying drug in Rheumatoid Arthritis (RA).
Nevertheless, adverse events affecting the lung are described and may be considered a limitation when prescribing MTX for RA patients with previous lung diseases. There are no definitive recommendations regarding the use of MTX in patients with RA and Interstitial Lung Disease (ILD). Objectives: To perform a Systematic Literature Research (SLR) about the safety of MTX in patients with RA and ILD.
Methods: The 3E 2007-2008 is a multi-national initiative to develop evidence and expert based recommendations for the
use of MTX in rheumatic diseases. Beside common clinical questions to be answered by an international bibliographic committee, there were specific questions to be developed by each national committee. The Brazilian committee performed a SLR focusing on the safety of MTX in patients with RA and ILD. Databases searched included Medline and Cochrane Clinical Trials from 1950 until June 2007 and EULAR/ACR abstracts 2005-2007. Keywords were RA, MTX, and a composite of ILD, pneumonitis, lung fibrosis, and pulmonary function. Results: One hundred and twelve studies were initial y retrieved for analysis that included predefined exclusion criteria.
Studies were excluded mainly due to smal sample size or design limitations. Only seven studies remained for the final analysis. One prospective study (n = 26; two years fol ow-up) suggests that MTX does not influence lung function in RA patients with ILD. Six retrospective studies (n = 1799) suggest that RA patients with ILD have an increased risk of developing acute pneumonitis when exposed to MTX. Nevertheless, these studies were heterogeneous regarding design and outcome definitions thus precluding a quantitative analysis.
Conclusion: There is some evidence that MTX does not interfere with the lung function in RA patients with ILD (Oxford
Category of Evidence: 2b). There is some evidence that pre-existing ILD is a risk factor for acute pneumonitis in RA patients treated with MTX (Oxford Category of Evidence: 3b). The Brazilian expert Committee concluded that RA patients with ILD may receive MTX, but on close surveil ance of their lung function (Grade of Recommendation = B). FRI0167 EFFICACY AND SAFETY OF VACCINATION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH
METHOTREXATE: A SYSTEMATIC LITERATURE RESEARCH.
B. A. Cruz*1, I. M. M. Laurindo2, M. B. Bertolo3, R. D. Giorgi4, I. A. Pereira5 1Rheumatology, Biocor Instituto, Nova Lima, 2Rheumatology, Medical School, USP, São Paulo, 3Rheumatology, Medical School, UNICAMP, Campinas, 4Rheumatology, Hospital dos Servidores do Estado, São Paulo, 5Rheumatology, Medical Background: Methotrexate (MTX) is the most prescribed disease modifying drug in Rheumatoid Arthritis (RA). There are
no definitive recommendations regarding efficacy and safety of vaccination in RA patients treated with MTX. There is also a concern about the possibility that immunization may increase disease activity in those patients. Objectives: To perform a Systematic Literature Research (SLR) about the efficacy and safety of vaccination in RA
Methods: The 3E 2007-2008 is a multi-national initiative to develop evidence and expert based recommendations for the
use of MTX in rheumatic diseases. Beside common clinical questions to be answered by an international bibliographic committee, there were specific questions to be developed by each national committee. The Brazilian committee performed a SLR focusing on the efficacy and the safety of vaccination in RA patients treated with MTX. Databases searched included Medline and Cochrane Clinical Trials from 1950 until June 2007 and EULAR/ACR abstracts 2005- 2007. Keywords were RA, MTX, vaccination and/or immunization. Results: Two hundred and six studies were initial y retrieved for analysis that included predefined exclusion criteria.
Studies were excluded mainly due to smal sample size or design limitations that did not permit comparison between RA patients treated with MTX, a control group of RA patients on other treatment and/or healthy subjects. Eight studies were kept for final analysis. Four prospective open studies (n = 615) that evaluated Influenza vaccination and two prospective open studies (n = 258) that evaluated hepatitis B vaccination suggest that both vaccines are effective, safe and do not interfere with disease activity. Two prospective open studies (n = 77) suggest that pneumococcal vaccination is safe, does not interfere with disease activity, but may be less effective in RA patients on MTX in comparison with RA patients on other treatments and healthy subjects. The studies were heterogeneous regarding design and outcome, thus precluding a
Conclusion: There is evidence that vaccination against Influenza, Hepatitis B, and Pneumococcus is effective and safe in
RA patients on MTX (Category of Evidence: 2b). Nevertheless, pneumococcal vaccination seems to be less effective in RA patients on MTX in comparison with healthy subjects and RA patients on other treatments. There are no data regarding the use of attenuated live viruses vaccinations in this population. The Brazilian expert Committee concluded that RA patients on MTX may receive vaccination against Influenza, Hepatitis B and Pneumococcus (Grade of

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