Disease activity and widespread pain are main contributors to patient-reported global health in axial spondyloarthritis: an analysis of 6064 patients.

Global health (GH) and health-related quality of life are patient priorities in axial spondyloarthritis (axSpA). Our objective was to assess the relative importance of disease-related factors including disease activity, and patient-related factors including comorbidities, to explain GH in axSpA. Post hoc cross-sectional analyses of 4 sets (COMOSPA, PERSPA, COMEDSPA, and DESIR) of patients fulfilling ASAS criteria for axSpA. GH was assessed through the ASAS Health Index (ASAS-HI) or the EuroQoL-5D-3L (EQ-5D). Disease-related factors included disease activity (ASDAS, psoriasis, arthritis, enthesitis, and CRP), disease duration, diagnostic delay, bamboo spine, and treatment. Non-disease-related factors included sociodemographic characteristics, comorbidities and chronic widespread pain. Multivariable logistic and linear regressions and partial variances (R2) were applied to identify independent determinants of GH. In 6064 patients (range 284-2756 across datasets), mean age ranged 38.9-45.8 years, 51-68% were male. GH was generally moderate: median ASAS-HI ranged 5.0-7.0. GH was explained by ASDAS (range of odds ratios, OR, 2.60-4.48) and chronic widespread pain (range of OR 2.19-8.39); other determinants included comorbidities and sociodemographic characteristics. Only 47-57% of the total variance in GH could be explained by the models; disease activity (partial variance, 16-26%) and chronic widespread pain (partial variance 12-15%) were the key contributing variables. A wide range of disease and non-disease-related variables usually collected in studies could only explain 47-57% of the variability in GH. Among these, disease activity and chronic widespread pain were most relevant and of similar magnitude of importance. These findings will be helpful for shared decision-making.

Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Suboptimal management of rheumatoid arthritis in France: a real-world study based on data from the French National Health Data System.

OBJECTIVES: The emergence of targeted therapy is changing rheumatoid arthritis (RA) management, but real-world data remain limited. This study aimed to describe real-world RA treatment patterns using data from a French national claims database. METHODS: This longitudinal study used the French Permanent Representative Sample (Echantillon Généraliste des Bénéficiaires) claims database. Patients with RA were identified between 2013 and 2017, with treatment patterns, persistence and adherence described. RESULTS: The study population included 2553 patients with RA. Disease-modifying antirheumatic drugs (DMARDs) were prescribed for 1512 (59.2%) patients, of whom 721 (47.6%) did not require discontinuation or treatment switch. There were 377 (24.9%) treatment discontinuations and 114 patients (7.5%) switched to a targeted DMARD (biological and synthetic (Janus kinase inhibitor) DMARDs). Among the 2315 patients with RA in 2017, almost half (n=1102, 47.6%) were not treated with a DMARD. Most (85.7%) received symptomatic treatment (analgesics (81.0%), steroids (49.2%), non-steroidal anti-inflammatory drugs (39.5%)). Of the 1142 treatment initiations identified, 713 (62.4%) were conventional synthetic DMARDs (csDMARDs), with methotrexate being the most frequent (n=553, 48.45%). One-year persistence rates varied between 55.9% (49.2-62.0%) for tumour necrosis factor inhibitors, and 63.4% (59.6-67.0%) for csDMARDs. Treatment adherence, assessed through medication possession ratio, varied between 71.9% and 90.8%, with ≥80% being the adherence cut-off. Almost half of DMARD initiations were associated with long-term (>6 months), high-dose oral steroid use (~7 mg/day prednisone equivalent). CONCLUSION: Despite a diverse therapeutic arsenal, there remains a medical need that is not covered by current RA management, which is frequently compensated for by overprescription of steroids.

Risk of Cancer After Initiation of Targeted Therapies in Patients With Rheumatoid Arthritis and a Prior Cancer: Systematic Review With Meta-Analysis.

OBJECTIVE: To determine the risk of recurrent or new malignancy with exposure to targeted disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA), axial spondyloarthritis (SpA), or psoriatic arthritis (PsA) and a history of cancer. METHODS: We performed a systematic search of the literature for articles published up to June 2019 that investigated adults with RA, axial SpA, or PsA who had a history of cancer and received biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs). We compared the risk of relapse or occurrence of new cancer between patients with and without bDMARDs. Rate ratios (RRs) with 95% confidence intervals (95% CIs) were estimated. The heterogeneity of the studies was evaluated by the Cochran Q test and the I2 statistic. RESULTS: We included 24 observational studies of chronic inflammatory arthritis; of those, 12 were included in the meta-analysis of RA patients receiving bDMARDs. As compared with RA patients with a history of cancer and not receiving bDMARDs, for those receiving any bDMARD, the overall RR for risk of neoplasia was 1.09 (95% CI 0.92-1.32; P = 0.31, I2  = 8%); with tumor necrosis factor inhibitors, it was 1.11 (95% CI 0.85-1.46; P = 0.45, I2  = 48%); and with rituximab, it was 0.79 (95% CI 0.41-1.53; P = 0.49, I2  = 0%). The RR for risk of recurrence for skin cancer was 1.32 (95% CI 1.02-1.72; P = 0.04, I2  = 0%) and for breast neoplasia 1.21 (95% CI 0.84-1.72; P = 0.31, I2  = 0%). CONCLUSION: Apart from skin cancers including melanoma, the risk of recurrent or new cancer is not increased with the initiation of bDMARDs for RA as compared with no bDMARDs.

MRI and ultrasonography for detection of early interphalangeal osteoarthritis.

OBJECTIVES: To assess the interest of MRI and ultrasonography (US) in identifying early and advanced interphalangeal (IP) OA. METHODS: We conducted a case-control study including patients with symptomatic hand OA (n=33) and young healthy volunteers (n=26). Proximal and distal IP joints were graded according to Kellgren and Lawrence (KL) grades. In OA patients, we separated IP joints into 2 groups: "at risk of OA" joints (potential early pre-radiographic OA joints, KL=0) and OA joints (KL=2-4). All IP joints from healthy participants were KL=0 and were considered strictly normal IP joints. Concurrently, synovitis, effusion, erosions, osteophytes, bone marrow lesions, cysts and cartilage space loss were graded by MRI and/or US. We assessed their prevalence, severity and diagnostic performance in hand OA and then compared normal IP joints from healthy participants and "at risk of OA" IP joints from OA patients as well as "at risk of OA" and OA IP joints from OA patients. RESULTS: The prevalence and grade of most MRI/US-detected lesions were higher in IP joints from OA patients than healthy participants. Except for osteophyte assessment, MRI seemed more sensitive than US. We found more MRI/US-detected lesions in "at risk of OA" IP joints than normal joints but also in OA than "at risk of OA" joints from OA patients. US appeared both sensitive and specific for detecting osteophytes in joints without radiographic abnormalities. CONCLUSIONS: MRI and US give good performance for detecting radiographic and pre-radiographic OA lesions and could be interesting tools to identify early hand OA.

Diagnostic performance of 18 F-FDG-PET/CT in inflammation of unknown origin: A clinical series of 317 patients.

BACKGROUND: Inflammation of unknown origin (IUO) is a challenging situation in internal medicine. OBJECTIVES: To describe the final diagnoses in IUO and assess the helpfulness of 18 F-fluorodesoxyglucose positron emission tomography with computerized tomography (18 F-FDG-PET/CT) in the diagnosis strategy. RESULTS: A total of 317 IUO patients with 18 F-FDG-PET/CT were enrolled. A diagnosis was reached in 228 patients: noninfectious inflammatory diseases (NIID) (37.5%), infectious diseases (18.6%), malignancies (7.9%), and non-systemic-inflammatory miscellaneous diseases (7.9%). The two leading causes of NIID were polymyalgia rheumatica and giant cell arteritis. 18 F-FDG-PET/CT results were classified as true positive in 49.8% of patients and contributory in 75.1% of overall IUO patients (after the complete investigation set and a prolonged follow-up). In multivariate analysis, only C-reactive protein minimum level (≥50 mg/L) was associated with the contributory status of 18 F-FDG-PET/CT. CONCLUSION: Within the wide spectrum of IUO underlying diseases, 18 F-FDG-PET/CT is helpful to make a diagnosis and to eliminate inflammatory diseases. Obese patients constitute a specific group needing further studies.

Associations Between Safety of Certolizumab Pegol, Disease Activity, and Patient Characteristics, Including Corticosteroid Use and Body Mass Index.

OBJECTIVE: To investigate the impact of baseline and time-varying factors on the risk of serious adverse events (SAEs) in patients during long-term certolizumab pegol (CZP) treatment. METHODS: Safety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time-varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO. RESULTS: Data were pooled from 8747 CZP-treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m2 or more versus a baseline BMI of 18.5 kg/m2 to less than 25 kg/m2 . Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m2 or more versus BMI of 18.5 kg/m2 to less than 25 kg/m2 and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m2 or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO. CONCLUSION: Age, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP-treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors.

Most Appropriate Conventional Disease-Modifying Antirheumatic Drug to Combine With Different Advanced Therapies in Rheumatoid Arthritis: A Systematic Literature Review With Meta-Analysis.

OBJECTIVE: In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies. METHODS: We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated. RESULTS: The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I2 = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I2 = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed. CONCLUSION: The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.

Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn's disease: a pooled analysis of 11 317 patients across clinical trials.

Objective: To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods: Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results: Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion: This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.

Similar alteration for mental and physical aspects in health-related quality of life over 5 to 8 years in 1347 patients with early arthritis and early inflammatory back pain.

INTRODUCTION: Health-related quality of life (HRQoL) is a priority for patients. The objectives were to describe the changes in HRQoL over 5-8 years in patients with early arthritis (EA) or early inflammatory back pain (IBP) and to explore factors associated to HRQoL. PATIENTS AND METHODS: In 2 prospective observational French cohorts (ESPOIR for EA patients and DESIR for early IBP patients), HRQoL was assessed regularly over 5-8 years, using the SF36 physical and mental composite scores (PCS and MCS, range 0-100). Disease activity was assessed by DAS28-ESR and ASDAS-CRP. Univariate and multivariate linear mixed-effect models and trajectory-based mapping were applied. RESULTS: In all, 1347 patients (701 EA and 646 early IBP) were analysed: mean age 48.4 ± 12.2 and 33.9 ± 8.7 years respectively; mean disease duration 3.4 ± 1.7 and 18.2 ± 10.8 months; and 76.3% and 55.0% females. At baseline, in EA, mean PCS and MCS were respectively 40.2 ± 9.1 and 40.4 ± 11.2 and, in early IBP, were respectively 38.5 ± 8.5 and 39.8 ± 10.9. Over follow-up, HRQoL mean levels improved mostly over the first 6 months (p <  0.001). Two trajectories were evidenced in both diseases. The 'good HRQoL' trajectory groups, i.e. 54-61% of patients, reached levels of HRQoL close to population norms. DAS28-ESR and ASDAS-CRP over time were related to PCS (range of explained variance 9-43%, p <  0.001 in the mixed models) but not to MCS. CONCLUSION: HRQoL was altered similarly for both physical and mental aspects in EA and early IBP. Disease activity only partly explained HRQoL: the drivers of HRQoL should be further explored.

Efficacy and safety of biological DMARDs modulating B cells in primary Sjögren's syndrome: Systematic review and meta-analysis.

OBJECTIVE: In this review, we summarise the clinical efficacy and safety of B-cell targeted therapies for primary Sjögren's syndrome (pSS). METHODS: A systematic literature review was conducted using databases including MEDLINE, EMBASE and Cochrane. Only articles reporting controlled or prospective studies of b-DMARDs modulating B cells in treatment of pSS were selected. The highest-quality studies were selected for meta-analysis. The primary outcome of interest was clinical efficacy at week 24 on fatigue, dryness, Schirmer test, salivary flow rate and the full ESSDAI score including biological domain. For the efficacy criteria used, the difference between rituximab and placebo groups was expressed as mean difference (MD). RESULTS: Eighteen articles (13 of rituximab, 3 of belimumab, 1 of epratuzumab and 1 of baminercept) were identified for detailed evaluation. 4 controlled randomised trials of rituximab treatment vs. placebo involving 300 patients were included for quantitative analysis. No significant differences were observed between groups in the meta-analysis of mean improvements between baseline and week 24 in fatigue VAS [MD -3,24 95% CI (-30,21 to 23,72)], oral dryness VAS [MD -8,41 95% CI (-35,06 to 18,24)], salivary flow rate [MD 0,04 95% CI (-0,03 to 0,11)] and Schirmer test [MD 0,35 95% CI (-2,13 to 2,82)]. Rituximab was relatively safe compared to placebo. CONCLUSION: Our review shows that rituximab is not effective in pSS with the designs and outcomes proposed in the trials. Controlled randomised trials are needed to prove the efficacy of belimumab and epratuzumab in this indication. The randomised controlled trial evaluating baminercept failed to achieve its primary endpoint.

The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort.

OBJECTIVE: To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. METHODS: Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. RESULTS: Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. CONCLUSION: Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis.

OBJECTIVES: To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA. METHODS: Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included. RESULTS: Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found. CONCLUSIONS: The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update.

In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.

[The rheumatoid hand]. / La main rhumatoïde.

Rheumatoid arthritis usually affects the hand (90%). Without treatment, joint damages and deformities lead to loss of the ability to grip, grasp, and pinch, often leaving the patient unable to perform the activities of daily living. Early treatment with DMARDs ± physical therapy is the best way to control the disease and prevent deformity, as well as disability, which often occurs when joints get damaged. Two decades later dramatic advances have been made in the medical therapy of RA with the expanded range of effective disease-modifying antirheumatic drugs. When a patient with RA develops joint damages in the hand or wrist that are unresponsive to medical management and injections therapy, surgical intervention may be necessary. Optimal care involves a team approach among the patient involving rheumatologists, physical therapists and hand surgeons. Patients with RA should be closely monitored in order to detect joint damages necessitating physical therapist or hand surgeon consultation.

Cost effectiveness of therapeutic interventions in ankylosing spondylitis: a critical and systematic review.

OBJECTIVES: This report reviews the cost effectiveness of different therapeutic interventions used in the treatment of ankylosing spondylitis (AS). METHODS: We performed a systematic search of the databases MEDLINE via PubMed, EMBASE and the Cochrane Library and used hand-searching to identify articles on cost effectiveness of therapies for adult patients with AS published up to November 2010. RESULTS: Of 135 articles, 13 studies were analysed. Two articles were on physical therapies, one article was on NSAIDs and ten articles were on tumour necrosis factor (TNF) inhibitors (infliximab = 6, etanercept = 2, infliximab and etanercept = 1 and adalimumab = 1). Of the latter, no article directly compared TNF inhibitors. Articles showed substantial heterogeneity in methodological approaches and thus results, which prevented us from any extensive comparison, data pooling or meta-analysis. The incremental cost-effectiveness ratio (ICER) for spa-exercise treatment was &U20AC;7465 (95% CI 3294, 14 686) per QALY. The ICERs for infliximab, etanercept and adalimumab were &U20AC;5307-237 010, &U20AC;29 815-123 761 and &U20AC;7344-33 303 per QALY, respectively. CONCLUSIONS: Modelling treatment strategies in chronic relapsing diseases such as AS presents specific challenges, as reflected in the variation in the cost-effectiveness results reported. Although quite variable, the cost-effectiveness ratios for AS therapies remain within an acceptable range.

Abatacept therapy and safety management.

OBJECTIVES: To develop and/or update fact sheets about abatacept treatment, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable 2. identification and review of publications relevant to each topic 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields (dermatologist, cardiologist, pediatric rheumatologist, endocrinologist, hematologist, immunologist, infectiologist), and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid arthritis (RA). They were members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society (Societe Francaise de Rhumatologie). Each fact sheet was revised by several experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of abatacept treatment; management of adverse effects and concomitant diseases that may develop during abatacept treatment; and management of common situations such as pregnancy, surgery, patient older than 75 years of age, and patients with co-morbidities (such as dialysis, hemoglobinopathy, or splenectomy). After a review of the literature and discussion among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of the abatacept treatment, management of patients with specific past histories, and specific clinical situations such as pregnancy 2. diseases other than RA, such as juvenile idiopathic arthritis, spondylarthropathies, or autoimmune diseases (systemic lupus erythematosus and other systemic autoimmune diseases) 3. models of letters for informing the rheumatologist and general practitioner 4. patient information about the use of abatacept in RA 5. and data on the new abatacept formulation for subcutaneous administration (approved by the FDA in August 2011 for patients with moderate-to-severe RA). CONCLUSION: These fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on abatacept. They will be available continuously on www.cri-net.com and will be updated at appropriate intervals.

Scleritis: a paradoxical effect of etanercept? Etanercept-associated inflammatory eye disease.

OBJECTIVE: To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept. METHODS: Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010. RESULTS: Three patients with seropositive RA developed scleritis 7-28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation. CONCLUSION: Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.

A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis.

OBJECTIVES: To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce. METHODS: A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed. RESULTS: While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small. CONCLUSIONS: This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.