The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis - A systematic review with meta-analysis.

This systematic review aimed to systematically investigate the literature on the effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis. For that, seven databases were searched for relevant randomized controlled trials. After the searches, 36 studies investigating 2281 participants were included. Risk of bias assessments were done by two independent reviewers using the Cochrane Risk of Bias tool 2. Random-effects meta-analyses were performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to judge the certainty of evidence. The evidence on benefits of exercise and physical activity programs on fatigue and sleep parameters in people with osteoarthritis and psoriatic arthritis was either lacking or inconclusive. There was very low to low certainty evidence for a slight benefit of exercise and physical activity programs on fatigue at short-term in people with ankylosing spondylitis and rheumatoid arthritis. However, the evidence was very uncertain for the medium- and long-term as well as for any sleep parameters. The results indicate that exercise and physical activity programs may offer some benefits on fatigue for people with arthritis in the short-term, although the best type of exercise remains uncertain. The available evidence on improvements in sleep was insufficient to draw strong conclusions.

Development and validation of a screening tool for SPondyloArthritis Screening in Sub-Saharan Africa: SpASSS questionnaire.

OBJECTIVE: To develop and validate a screening tool to identify patients with a high likelihood for Spondyloarthritis (SpA) in the Democratic Republic of the Congo (DR Congo). METHODS: The development of the SpA Screening questionnaire in Sub Saharian Africa (SpASSS) questionnaire followed 3 steps: The item generation was carried out by a systematic literature review according to the PRISMA guidelines on the clinical manifestations of SpA, interviewing clinical experts and the classification criteria for Spondyloarthritis. The candidate questions were tested in a population of 50 consecutive patients with confirmed diagnosis of spondyloarthritis, in a control population of rheumatic disease excluding SpA and in a group of 200 non-rheumatic participants, randomly chosen in the general population for question reduction and validation. Descriptive statistical analyses were performed to assess socio-demographic characteristics and response distribution for each item. Their diagnostic performance was investigated using ROC curves. For validation, principal component analysis was performed using factor analysis. Referral strategy score for SpA was determined by adjusted Cronbach's alpha coefficient. RESULTS: Mean ± SD age of SpA cases was 41.8 ± 14.4 years, 56% were men compared to diseased controls 60.0 ± 12.5 years, 28.7% men (p < 0.001). 14/20 items showed a statistically significant difference (p < 0.05) between SpA cases and control groups. All items were factorable and 6 components were identified. Only the two first components (C1 with 8 items, C2 with 3 items) showed a significant threshold for reliability in detection of suspected SpA with a Cronbach's alpha of 0.830 and 0.708. All validated items of these two components showed the global reliability threshold with α-adjusted Cronbach calculated at 66.9%. The performance for correctly screening SpA was demonstrated with an area under the curve of 0.938 (0.884-0.991) and 0.794 (0.728-0.861) for C1 and C2 respectively. CONCLUSIONS: This validation and item reduction of the SpASSS questionnaire for SpA might identify patients to refer for case ascertainment and will help conducting future epidemiological and clinical studies in the DR Congo. STRENGTHS AND LIMITATIONS OF THIS STUDY: • To the best of our knowledge, this is the first study in Sub-Saharan Africa based on local data to develop a screening tool for SpA in the population for epidemiological and clinical use. • Referral strategies based on context-specific data are necessary to provide accurate case definition and epidemiological data, thus reducing methodological bias. • In the SpA group, no discrimination was made regarding SpA subtypes, disease duration, activity and severity.

Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.

OBJECTIVES: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). METHODS: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. RESULTS: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). CONCLUSIONS: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography.

OBJECTIVE: To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). METHODS: CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. RESULTS: In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. CONCLUSIONS: Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

The European ankylosing spondylitis infliximab cohort (EASIC): a European multicentre study of long term outcomes in patients with ankylosing spondylitis treated with infliximab.

OBJECTIVES: To study the long-term efficacy and safety of treatment with infliximab in patients with ankylosing spondylitis (AS) in a real life setting. METHODS: AS patients from 6 European countries who had finished the 2-year trial ASSERT were invited to participate in the open- label investigator-driven study EASIC. At baseline, 2 groups were formed: patients of group 1 had not been treated with infliximab after ASSERT, while those of group 2 had continuously received it. Patients of group 1 were further subdivided in group 1a: patients with a relapse and 1b: in remission. All patients of group 1a and 2 continuously received infliximab for 96 weeks, mean dose 5 mg/kg, intervals 6-8 weeks. Patients of group 1b were also treated in case of relapse. RESULTS: A total of 103/149 patients (69%) were included in EASIC, 1.3 ± 0.9 years after the end of ASSERT: 9 in group 1a, 5 in group 1b and 89 in group 2. Most patients were male (83%), mean age 44 years. Most patients of group 2 completed the trial (86%) vs. only 5 of group 1 (33%) - mostly due to allergic reactions after readministration of infliximab. In total, there were 22 drop-outs due to 6 adverse events, 4 lack of efficacy, 3 planned pregnancy. All standard assessments indicated beneficial values over time, at week 96 significantly better than at baseline of ASSERT. CONCLUSIONS: The majority of patients were continuously and successfully treated with infliximab for 5 years, whereas discontinuation and reintroduction of therapy was less satisfactory due to the frequent occurrence of hypersensitivity reactions. Anti-TNF therapy with infliximab proved to be effective and safe on a long-term basis.

Osteoporosis in rheumatoid arthritis and ankylosing spondylitis.

Bone is a target in many inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The generalized effect of inflammation on bone may result in a decreased quality of bone and is associated with an increased risk of fractures and deformities, both in RA and AS. RA is characterized by periarticular osteopenia, systemic osteoporosis and bone erosions. Periarticular osteopenia and bone erosions are mainly correlated with disease activity. Unlike postmenopausal osteoporosis, osteoporosis in RA is more characterised by marked loss of bone in the hip and the radius, while the axial bone is relatively preserved. In general, several cross-sectional studies documented a lower bone mineral density in patients with RA, with a two-fold increase in osteoporosis compared to age- and sex-matched controls and relates to an increased fracture risk. Several factors contribute to the increased risk: older age, little exercise, long-term use of corticosteroids, and high disability index. AS is characterized by an increase in bone fragility due to reduced bone mineral density. The reported prevalence of osteoporosis in AS patients varies largely. The large variation reflects the difficulties in assessing BMD in AS due to new bone formation. Bone fragility is also due to changes in structural properties resulting from inflammation-induced bone failure in the spine in combination with reduced capacity of shock absorption leading to vertebral fractures. Different types of spinal fractures in patients with AS are described, including wedging. Wedging vertebral fractures contribute to hyperkyphosis and impaired physical function. In contrast to RA , bone loss in AS is accompanied by new bone formation. The pathophysiology of osteoporosis in RA and AS probably is fundamentally similar, but with different clinical phenotypes. The implications for therapeutically intervening in its occurrence and progression might be fundamentally different.

Detection and identification of antinuclear antibodies (ANA) in a large community hospital.

OBJECTIVE: Antinuclear antibodies (ANA) and their identification are important diagnostic tools in rheumatic diseases. We aimed to determine their prevalence in samples referred for ANA testing and to identify factors predicting more specific reactivities. METHODS: We analyzed the first sample of 6422 consecutive patients for ANA. Positive samples were analyzed by indirect immunofluorescence (IIF) on Crithidia luciliae and by line immunoassay. We used multivariate logistic regression to detect predicting variables. RESULTS: 42.6% of all patients were ANA positive of which 13.0% showed > or = one extractable nuclear antigen (ENA) reactivity with anti-SSA/Ro (5.5%), anti-SSB/La (2.9%), anti-Cenp-B (2.5%) and anti-histones (2.2%) as the most prevalent antibodies. Anti-double-stranded DNA antibodies (dsDNA) were present in 1.0%. The strongest overall predictor was ANA intensity regardless of pattern. Cenp-B however was best predicted by pattern. Anti-dsDNA and anti-histone were more frequent in samples with a homogenous as compared with a speckled pattern. Anti-SSA and anti-SSB were more frequent in females and anti-Sm in patients < or = 30 years. CONCLUSIONS: The best overall predictor of antibodies to ENA or dsDNA is ANA intensity. Anti-Cenp-B is however best predicted by pattern. Samples with low ANA intensity (1+) may not need further testing unless a high clinical suspicion of ANA-associated disease.

Classification models for disease: the effect of associations between markers on calculating the risk for disease by likelihood ratio products.

OBJECTIVES: The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. PATIENTS AND METHODS: Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. RESULTS: When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk. CONCLUSIONS: We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal.

OBJECTIVE: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. METHODS: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as "paper patients" by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. RESULTS: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p<0.001) was strongly associated with the classification of axial SpA. The knowledge of MRI findings led to a change in the classification of 21.1% of patients. According to the first set of candidate criteria (sensitivity 97.1%; specificity 94.7%) a patient with chronic back pain is classified as axial SpA in the presence of sacroiliitis by MRI or x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). CONCLUSION: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.

Treatment recommendations for psoriatic arthritis.

OBJECTIVE: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. METHODS: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. RESULTS: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. CONCLUSIONS: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.

Activation of nuclear factor kappa B and mitogen activated protein kinases in psoriatic arthritis before and after etanercept treatment.

OBJECTIVE: To study activation of intracellular pathways depending on nuclear factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of patients with psoriatic arthritis before and after treatment with etanercept. METHODS: Synovial biopsies were obtained by needle arthroscopy of the knee in 9 patients with active psoriatic arthritis before the initiation of etanercept. Follow-up biopsies were taken in the same knee after 6 months. Synovitis was studied by histology. Pathway activation was studied by immunofluorescense for phosphorylated ERK, phosphorylated p38, phosphorylated JNK or phosphorylated inhibitor of kappa B (IkappaBalpha) using digital image analysis. RESULTS: Histological severity scores were significantly reduced after etanercept treatment. Activation of NFkappaB signaling was found in the lining layer, and in infiltrating and peri-vascular cells in the sublining zone. Activated p38 was present in both lining and sublining layer. In the sublining layer, positive cells were found in inflammatory infiltrates, in perivascular zones and in the endothelium. Activated ERK was mainly present in the sublining layer, both in mononuclear cell infiltrates and perivascularly. Occasional positive cells were found in the lining layer. Activation of JNK was recognized in cells of the lining layer, in some of the sublining cell infiltrates and the perivascular compartment. CONCLUSIONS: Etanercept therapy resulted in a significant decrease in NFkappaB, JNK and ERK, but not in p38 activation. Persistent activation of these pathways, albeit reduced, may trigger positive feedback loops and flares of arthritis after cessation of etanercept.

Dissemination and evaluation of the ASAS/EULAR recommendations for the management of ankylosing spondylitis: results of a study among 1507 rheumatologists.

BACKGROUND: Ten ASAS/EULAR recommendations for the management of ankylosing spondylitis (AS) were published in 2006. OBJECTIVES: (a) To disseminate and (b) to evaluate conceptual agreement with, and (c) application of, these recommendations as well as (d) potential barriers to the application. METHODS: A questionnaire was sent to rheumatologists in 10 countries. It included (a) the text of the recommendations; (b) rheumatologists' demographic variables; (c) two numerical rating scales from 1 to 10 for each recommendation: conceptual agreement with, and application of, the recommendation (10 indicates maximal agreement and maximal application); and (d) a list of potential barriers to the application of the recommendation. Statistical analysis included descriptive and multivariate analyses. RESULTS: 7206 questionnaires were sent out; 1507 (21%) were returned. Of the 1507 answering rheumatologists, 62% were men, mean (SD) age 49 (9) years, and 34% had an academic position. Conceptual agreement with the recommendations was high (mean (SD) for all recommendations 8.9 (0.9)). Self-reported application was also high (8.2 (1.0)). The difference between agreement and application varied across recommendations and countries. The most pronounced discrepancies were reported for use of anti-tumour necrosis factor drugs in a few countries, with funding as the most commonly reported barrier for application of this recommendation. CONCLUSION: This large project has helped the dissemination of the ASAS/EULAR recommendations for the management of AS and shows that conceptual agreement with the recommendations is very high. The project also highlights inequalities in access to healthcare for European citizens with AS.

Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2.

OBJECTIVE: To evaluate the effect of infliximab on progression of structural damage over 1 year in patients with active psoriatic arthritis (PsA) enrolled in the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. METHODS: In this double-blind, placebo-controlled study, 200 patients with active PsA were randomly assigned (1:1 ratio) to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6, and every 8 weeks thereafter through week 54. At week 24, patients initially assigned to receive placebo crossed over to receive infliximab (5 mg/kg). Based on predefined criteria, patients randomized to receive placebo could enter early escape by receiving infliximab (5 mg/kg) starting at week 16, and patients randomized to receive infliximab could have the dose increased to 10 mg/kg starting at week 38. Patients were analyzed according to the treatment they were randomized to receive. Radiographs of hands and feet were obtained at baseline and at weeks 24 and 54. Two readers blinded to treatment assignment and radiograph sequence independently evaluated erosions and joint space narrowing using the Sharp/van der Heijde scoring method modified for PsA. RESULTS: At week 24, patients randomized to receive infliximab 5 mg/kg had significantly less radiographic progression compared with patients randomized to receive placebo, with mean +/- SD changes from baseline in the total Sharp/van der Heijde score of -0.70 +/- 2.53 and 0.82 +/- 2.62, respectively (P < 0.001). At week 54, mean +/- SD changes from baseline in the total Sharp/van der Heijde score were -0.94 +/- 3.40 in patients randomized to receive infliximab and 0.53 +/- 2.60 in those receiving placebo/infliximab (P = 0.001). CONCLUSION: Infliximab significantly inhibits radiographic progression in patients with PsA as early as 6 months after starting treatment, and the beneficial effect continues through 1 year of infliximab therapy.

Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial.

OBJECTIVE: To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis (PsA) enrolled in the IMPACT 2 trial. METHODS: In this double blind, placebo controlled, phase III study, 200 patients with active PsA were randomised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter through 1 year. Patients with persistent disease activity could enter early escape at week 16, and all remaining placebo patients crossed over to infliximab at week 24. Patients randomised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38. Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses. Major clinical response (that is, maintenance of ACR 70 response for 24 continuous weeks) was assessed for the first time in PsA. RESULTS: Through 1 year of treatment, 58.9% and 61.4% of patients in the randomised infliximab and placebo/infliximab groups, respectively, achieved ACR 20; corresponding figures for PASI 75 were 50.0% and 60.3%. At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent with that seen through week 24. Two malignancies occurred: basal cell skin cancer (placebo) and stage I Hodgkin's lymphoma (infliximab). CONCLUSION: Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment.