Impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab in axial spondyloarthritis (axSpA): data from the French multicentre retrospective FORSYA study.

OBJECTIVE: To compare the 1-year retention rate of secukinumab in axial spondyloarthritis (axSpA) and its predisposing factors with regard to its time of initiation (eg, right after or remotely from its launch). METHODS: Study design: Retrospective multicentre French study of patients with axSpA. Study periods: Two cohorts were evaluated regarding the time of initiation of secukinumab: cohort 1 (C1)-between 16 August 2016 and 31 August 2018-and cohort 2 (C2)-between 1 September 2018 and 13 November 2020. STATISTICAL ANALYSIS: The 1-year retention rate of secukinumab was estimated using the Kaplan-Meier method, and the log-rank test was used to compare the retention curves of the two cohorts. Preselected factors (eg, disease characterristics, line and time of secukinumab initiation) of secukinumab retention at 1 year were analysed by univariate and multivariate Cox model regression. RESULTS: In total, 906 patients in C1 and 758 in C2 from 50 centres were included in the analysis. The 1-year retention rate was better in C2 (64% (61%-68%)) vs C1 (59% (55%-62%)) (HR=1.19 (1.02-1.39); p=0.0297). In the multivariate analysis, the line of biologic therapy was the single predictive factor of the 1-year retention rate of secukinumab picked up in both cohorts, with a better retention rate when prescribed as first-line biologic therapy. CONCLUSION: The better secukinumab retention rate remotely from its launch is explained by its use at an earlier stage of the disease, suggesting a change in the behaviour of prescribing physicians. Our results emphasise the relevance of iterative evaluations of routine care treatments.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

Disease activity outcome measures are only available in half of the electronic medical files of patients with axial spondyloarthritis followed in an outpatient clinic: the results of an audit of a tertiary-care rheumatology department.

Current recommendations for management of patients with axial spondyloarthritis (axSpA) include regular collection of validated disease activity outcomes. This study aimed at evaluating the proportion of patients for whom validated outcome measures were available on their electronic medical reports (EMR), and the factors associated with the presence of such information on the EMR. We performed a cross-sectional monocentric observational study, including patients with an axSpA diagnosis who attended an outpatient visit between February, 2018 and February, 2019. Patients (demographics, disease characteristics, treatment) and physician characteristics (age, gender) and the disease activity outcome measures (BASDAI, CRP and ASDAS, and the items allowing to calculate them) were retrieved from the EMR. The proportion of patients in which disease activity outcome measures were available in the EMR was calculated, and the association between the presence of such outcomes and patients and physician's characteristics was evaluated. 320 EMR of axSpA patients seen in the outpatient clinic were examined. Among them, 131 (41%) and 123 (38.4%) had a BASDAI + CRP and an ASDAS reported, respectively, but at least one was available in 178 (55.6%) of the EMR. The most frequently reported disease activity items were duration of morning stiffness (n = 230, 72%) and CRP (n = 224, 70%). Only previous participation on a systematic holistic review was independently associated with a reported disease activity outcome. Thus, implementation of recommendations with regard to regularly collecting disease activity outcome measures is not optimal. The participation in educational programs including self-assessment educational programs might be a key to improve such implementation.

EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.

OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.

Adherence to and patient's knowledge of self-management of subcutaneous biologic therapy in chronic inflammatory rheumatic diseases: results of a multicentre cross-sectional study.

OBJECTIVES: Non-adherence to biologic therapy is an issue in chronic inflammatory rheumatic diseases (CIRDs) and might be related to poor patient knowledge of the risk of these therapies. Our aim here was to evaluate the level of patient adherence to and knowledge of self-care safety skills for biologic therapy. METHODS: This was a multicentre, cross-sectional study in which out-patients visited an office- or hospital-based rheumatologist. All the patients received subcutaneous biologic therapy for CIRDs. We collected data on: 1. the level of CIRD patient adherence to current subcutaneous biologic therapy using both the self-administered Compliance Questionnaire Rheumatology 5 items (CQR5) and a simple adherence question; 2. patients' knowledge of self-management of biologic therapy by the self-administered BIOSECURE questionnaire; 3. sources of information related to biologic therapy. RESULTS: In all, 285 patients (rheumatoid arthritis, n=103; spondyloarthritis, n=153; psoriatic arthritis, n=25) were enrolled by 19 rheumatologists. The mean (SD) biologic therapy duration was 5.9 (4.9) years. Adherence to the current biologic therapy was high (79.3% and 57.5% according to the CQR5 questionnaire and the adherence question, respectively). Level of knowledge of self-care safety skills (median BIOSECURE score 71) was in the acceptable range. Level of adherence and level of knowledge of self-care safety skills for biologic therapy were not associated. Patients declared that the main sources of information were their rheumatologist (92.6%) and the rheumatology team (30.5%). CONCLUSIONS: According to the patients' estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).

Evaluation of the impact of a nurse-led program of systematic screening of comorbidities in patients with axial spondyloarthritis: The results of the COMEDSPA prospective, controlled, one year randomized trial.

OBJECTIVE: To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). PARTICIPANTS: consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist) THE PROGRAM: A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit. TREATMENT ALLOCATION: random allocation (i.e. either this program or an educational program not presented here and considered here as the control group). MAIN OUTCOME: change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management). RESULTS: 502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p<0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p<0.01). CONCLUSIONS AND RELEVANCE: This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.

A randomised, double-blind, placebo-controlled study assessing the efficacy of high doses of vitamin D on functional disability in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the short-term efficacy of vitamin D (cholecalciferol) supplementation on functional disability in RA patients. METHODS: 1) Patients: RA (ACR 1987 revised criteria) in non-remission (DAS28 >2.6) whose treatment was not expected to be changed over a 3-month period following inclusion and presenting with vitD deficits (serum 25OHD <30ng/mL). 2) Study design: prospective randomised placebo-controlled trial (NCT02243800). 3) Study arms: either vitD ampoules (cholecalciferol 100,000IU) or placebo. 4) Outcome measures: primary: improvement in patients' functional disability using the Health Assessment questionnaire (HAQ); secondary: improvement in DAS28ESR, DAS28CRP, ESR, CRP, RAID score, fatigue (EVA and FACIT), and SF36. RESULTS: Overall, 59 patients were included, 83.1% females, aged 59.8±10.9 years on average, with RA for 17.0±9.7 years. Thirty patients received placebo and 29 vitD. At 6 months, HAQ scores tended to be increased in the placebo group (+0.08±0.25), while slightly numerically decreased in the vitD group (-0.03±0.23) (p=0.11). After adjusting for age, gender, season, and initial vitD status, the between-group difference achieved statistically significance (p=0.046). After adjusting for age, gender, season, and initial vitD status, there was no significant difference in the secondary criteria between the 2 groups except for ESR and CRP (p=0.002 and 0.04, respectively). CONCLUSIONS: In this randomised, double-blind, placebo-controlled clinical trial in patients with RA and VitD deficiency, high doses of cholecalciferol resulted in a statistically significant improvement in functional disability at month 6, which, however, was clinically not relevant.

Vitamin D status in spondyloarthritis: results of the ASAS-COMOSPA international study.

OBJECTIVES: Spondyloarthritis (SpA) encompasses both bone production and bone loss, and the latter is particularly linked to inflammation. Vitamin D deficiency has been associated with several inflammatory conditions (i.e. cardiovascular disease, rheumatoid arthritis), but it has been poorly evaluated in SpA patients. We aimed to a) describe the prevalence of vitamin D deficiency in SpA patients worldwide; b) compare SpA patients with and without vitamin D deficiency in terms of disease phenotype, activity severity and comorbidities. METHODS: This is an ancillary study of the ASAS-COMOSPA study initiative, an international cross-sectional study of patients with SpA. Demographics, patients' phenotype, disease activity/severity measures and comorbidities were assessed. Serum 25-hydroxyvitamin D (25OHD) deficiency was defined as <20 ng/mL (<50 nmol/L). STATISTICAL ANALYSIS: a) prevalence of vitamin D deficiency; b) comparison of the disease presentation/activity/severity and comorbidities in the group of patients with and without vitamin D deficiency by bi-variable and multivariable analysis. RESULTS: Vitamin D deficiency was observed in 527(51.2%) of the 1030 patients with available data who were not receiving any supplementation. Vitamin D deficiency was independently associated with the presence of radiographic sacroiliitis (OR=2.1 [95%CI1.3; 3.3]) and a 25OHD measured in winter and spring (OR=1.88 [95%CI 1.2; 2.9]). No independent association between vitamin D deficiency and comorbidities was found. CONCLUSIONS: This study suggests that vitamin D deficiency is common in SpA worldwide and is associated with season but also with more severe forms of SpA.

Evaluation of Vitamin D Status in Rheumatoid Arthritis and Its Association with Disease Activity across 15 Countries: "The COMORA Study".

The aims of this study are to evaluate vitamin D status in 1413 RA patients of COMORA study from 15 countries and to analyze relationship between patients' RA characteristics and low levels of vitamin D. All demographic, clinical, and biological data and RA comorbidities were completed. The results showed that the average of vitamin D serum dosage was 27.3 ng/mL ± 15.1 [0.1-151]. Status of vitamin D was insufficient in 54.6% and deficient in 8.5% of patients. 43% of RA patients were supplemented with vitamin D and absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency (p < 0.001). Finally, our study shows that the status of low levels of vitamin D is common in RA in different countries and under different latitudes. Absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency. Low levels of vitamin D were associated with patients characteristics (age, BMI, and educational level), RA (disease activity and corticosteroid dosage), and comorbidities (lung disease and osteoporosis therapy). This suggests the need for a particular therapeutic strategy to improve vitamin D status in RA patients.

Prevalence of vitamin D deficiency in rheumatoid arthritis and association with disease activity and cardiovascular risk factors: data from the COMEDRA study.

OBJECTIVES: The relationship between vitamin D and rheumatoid arthritis (RA) activity remains controversial. RA is a cardiovascular risk factor. A low level of vitamin D may increase blood pressure (BP) and decrease HDL-cholesterol. We aimed to determine the prevalence of vitamin D deficiency in RA patients compared to controls, and also to investigate the relationship between vitamin D and RA activity, and between vitamin D and cardiovascular risk factors. METHODS: Patients in the COMEDRA study with established inactive RA (1987 ACR criteria) were matched with subjects from the NUTRINET-SANTE cohort (age, gender, latitude, sampling season). Vitamin D deficiency was defined as <10 ng/mL, and insufficiency as 10 to 29.9 ng/mL. RESULTS: Eight hundred and ninety-four RA patients were analysed, of which 861 were matched with controls. The prevalence of vitamin D insufficiency and deficiency was lower in RA patients than in controls: 480 (55.8%) vs. 508 (59%) and 31 (3.6%) vs. 45 (5.23%), respectively; p=0.04. There was an inverse correlation between vitamin D levels and RA activity assessed by DAS28-CRP (p=0.01), SDAI (p<0.001) and CDAI (p=0.001), but not DAS28-ESR after adjustment for age, gender, inclusion season, body mass index (BMI), vitamin D supplementation, disease duration, RF or anti-CCP status and RA treatments. Vitamin D levels were inversely correlated with BMI (p<0.001), but not with BP, total cholesterol, LDL-cholesterol, HDL-cholesterol or blood glucose. CONCLUSIONS: This study demonstrates that vitamin D is inversely correlated with RA activity and BMI, but not with other cardiovascular risk factors.

Vitamin D, disease activity and comorbidities in early spondyloarthritis.

OBJECTIVES: To assess the vitamin D status in patients presenting inflammatory back pain suggestive of axial spondyloarthritis and to assess the relationship between vitamin D status and disease activity/severity; comorbidities at baseline and during the first two years of follow-up. METHODS: DESIR is a prospective, multicentre, observational study. Vitamin D deficiency was defined as <50 nmol/L and severe deficiency less than 25 nmol/L. Clinical variables were collected at each six month interval visits during the two-year follow-up. RESULTS: A total of 700 patients were analysed. The mean vitamin D was 54.2±28.7 nmol/L. Severe deficiency were observed in 11.7% versus 5% in the DESIR cohort versus the French population respectively. In the DESIR cohort, after adjusting for season and ethnicity, vitamin D deficiency remained significantly associated with presence of radiological sacroiliitis, higher ASDAS score and elevated BASDAI. Such association was also found between vitamin D deficiency and the mean value of disease activity/severity parameters during the two-year follow-up. Otherwise, vitamin D deficiency was significantly associated with the presence of baseline abdominal obesity (OR=1.65 [1.05-2.61], p=0.03), low HDL (OR=1.71 [1.14-2.55], p=0.01) and presence of metabolic syndrome (OR=2.20 [1.04-4.64], p=0.03) at baseline. CONCLUSIONS: We found a higher percentage of patients with severe vitamin D deficiency in early axial spondyloarthritis. Vitamin D deficiency was associated with higher disease activity and severity and presence of metabolic syndrome. Further longitudinal studies are required to evaluate the interest of vitamin D supplementation on the long-term outcome of the disease.

Randomised, controlled trial of avocado-soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study.

OBJECTIVE: To assess the ability of avocado-soybean unsaponifiable-Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). METHODS: Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of 'progressors' (JSW loss≥0.5 mm) between groups. RESULTS: 399 patients were randomised (345 kept in the FAS), aged 62 (35-84) years, 54% women, mean body mass index 27 (SD 4) kg/m(2), mean symptom duration 4 (SD 5) years, 0-100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (-0.638 mm vs -0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. CONCLUSIONS: 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment.

Evidence of the symptomatic and structural efficacy of methotrexate in daily practice as the first disease-modifying drug in rheumatoid arthritis despite its suboptimal use: results from the ESPOIR early synovitis cohort.

OBJECTIVE: To describe the use of MTX in early arthritis (EA) in daily clinical practice and to evaluate its 6-month symptomatic efficacy and 12-month structural efficacy. METHODS: Patients included in the French observational ESPOIR cohort were assessed. Evaluation of the symptomatic and structural efficacy was performed by generalized linear regression after adjustment on propensity score (PS) in the group of patients receiving at least 3 months of MTX vs the ones receiving any other treatment except LEF, SSZ or TNF inhibitors. RESULTS: Within the first 6 months of follow-up of 777 EA patients, 59% received a DMARD, which was MTX in 68% (N = 313) of patients. The mean dose of MTX was 12.7 ± 3.8 mg/week. Only 53.7% of the patients received folic acid supplementation. MTX was initiated in patients with more active and severe disease. At 6 months, in unadjusted analysis, patients starting MTX had a significantly higher DAS-28 (3.58 vs 3.23; P = 0.001) and a significantly higher HAQ (0.60 vs. 0.48; P = 0.01) compared with controls. After adjustment by PS, there were no significant differences. Adjustment for the PS also revealed a statistically significant decrease in the radiological progression at 12 months in the MTX group [total Sharp-van der Heijde score (SHS), 1.05 ± 0.29 vs 2.02 ± 0.29, P = 0.025]. CONCLUSION: This study confirms the symptomatic and structural efficacy of MTX in EA in daily practice despite the non-optimal use of MTX, including low doses and infrequent concomitant folic acid supplementation.

Symptomatic slow-acting drugs for osteoarthritis: what are the facts?

The term "symptomatic slow-acting drugs for osteoarthritis" (SySADOA) was coined more than a decade ago to designate medications and/or nutritional supplements used to alleviate the manifestations of osteoarthritis in the long-term. Their efficacy has always been a focus of considerable skepticism. However, a critical reappraisal of the available data, which include results of carefully designed clinical trials conducted in accordance with Good Clinical Practice guidelines, strongly suggests a therapeutic effect. The effects of SySADOA need to be determined based, in particular, on treatment objectives (symptom relief, decreased use of nonsteroidal antiinflammatory drugs and other conventional agents, decreased radiographic progression, and decreased use of joint replacement surgery). In addition, the characteristics of the patients who are most likely to benefit from SySADOA need to be identified.

Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion.

OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

The use of glucosamine therapy in osteoarthritis.

Glucosamine products have been used extensively for the management of pain in osteoarthritis. This paper reviews the most recent clinical and experimental studies regarding its efficacy and safety. Although clinical trials include methodologic flaws and publication bias, glucosamine is likely an effective therapy for the symptomatic management of osteoarthritis. In turn, definite proof for chondromodulating effect requires well-conducted clinical trials. In North America, glucosamine is an over-the-counter dietary supplement and preparations made by different manufacturers may vary. There is also a need to standardize this therapy and allow practitioners to give patients suitable advice. An ongoing long-term clinical trial in the US will possibly permit to investigate the clinical relevance of these results and give appropriate recommendations.

The use of glucosamine therapy in osteoarthritis.

Glucosamine products have been used extensively for the management of pain in osteoarthritis. This paper reviews the most recent clinical and experimental studies regarding its efficacy and safety. Although clinical trials include methodologic flaws and publication bias, glucosamine is likely an effective therapy for the symptomatic management of osteoarthritis. In turn, definite proof for chondromodulating effect requires well-conducted clinical trials. In North America, glucosamine is an over-the-counter dietary supplement and preparations made by different manufacturers may vary. There is also a need to standardize this therapy and allow practitioners to give patients suitable advice. An ongoing long-term clinical trial in the US will possibly permit to investigate the clinical relevance of these results and give appropriate recommendations.