The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire: predicting clinical arthritis development.

OBJECTIVE: There is a need to better define symptom characteristics associated with arthritis development in individuals at risk of rheumatoid arthritis (RA). We investigated whether reported symptoms in at-risk individuals could predict arthritis development and whether predictive symptoms differed between seropositive and seronegative at-risk individuals. METHOD: At-risk individuals from four cohorts (Netherlands, UK, Sweden, and Switzerland) completed the Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire. Participants had either (i) anti-citrullinated protein antibodies and/or rheumatoid factor, or (ii) relevant symptoms with or without RA antibodies. Follow up was ≥ 24 months or until clinical arthritis development. Stepwise forward selection created SPARRA prediction models for the combined group and for a seropositive subgroup. RESULTS: Of 214 participants, the mean age was 50 years, 67% were female, and 27% (n = 58) developed clinical arthritis after a median time of 7 months. Four symptoms predicted arthritis development: self-reported joint swelling, joint pain moving from side to side (combined group only), feeling pins and needles in the joints, and often feeling fatigued (predicting non-arthritis). CONCLUSION: Specific symptoms can provide useful information to estimate a person's RA risk. Differences in predictive symptoms between seropositive and seronegative at-risk individuals need to be further investigated. Future research is needed to determine whether changes in symptoms over time improve prediction and to determine the value of SPARRA in optimizing the selection of individuals who need to consult a rheumatologist.

Greater trochanteric pain syndrome: predicting who will respond to a local glucocorticoid injection.

Objectives: This study aimed to explore whether certain clinical tests or a rapid improvement in lateral hip pain following periarticular injection are predictive of subsequent efficacy of local glucocorticoid (GC) injection in greater trochanteric pain syndrome (GTPS).Method: This secondary analysis of a randomized controlled trial of an injection of GC and local anaesthetic (LA) versus placebo included 44 patients with GTPS. Two subgroups of patients were defined: (i) 30 min responders, reporting a decrease of ≥ 50% of the initial pain at 30 min post-injection; and (ii) positive triple test, presenting a combination of three positive clinical tests (30-second single-leg stance, FABER, and Lequesne). Median level of numeric rating scale for pain at 1 month was the primary outcome. Interaction analysis of treatment effect in the subgroups was performed using a linear regression adjusting for pain at baseline.Results: Sixteen patients (36%) were 30 min responders. In this group, GC treatment was associated with a significant improvement in pain at 1 month compared to non-responders (p = 0.03). The 30 min response was not associated with the use of LA. Positive triple test (22% of patients) was associated with higher pain scores at baseline (p = 0.03). In this group, patients who received placebo had significantly more pain at 1 month than those with the cortisone injection (p = 0.04).Conclusion: Patients with GTPS who present a rapid decrease in pain after periarticular injection, and those who display a combination of three specific clinical tests, are more likely to benefit from an injection with GC and anaesthetic.

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland.

BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.

Towards standardized patient reported physical function outcome reporting: linking ten commonly used questionnaires to a common metric.

OBJECTIVES: Outcomes obtained using different physical function patient reported outcome measures (PROMs) are difficult to compare. To facilitate standardization of physical function outcome measurement and reporting we developed an item response theory (IRT) based standardized physical function score metric for ten commonly used physical function PROMs. METHODS: Data of a total of 16,386 respondents from representative cohorts of patients with rheumatic diseases as well as the Dutch general population were used to map the items of ten commonly used physical function PROMs on a continuous latent physical function variable. The resulting IRT based common metric was cross-validated in an independent dataset of 243 patients with gout, osteoarthritis or polymyalgia in which four of the linked PROMs were administered. RESULTS: Our analyses supported that all 97 items of the ten included PROMs relate to a single underlying physical function variable and that responses to each item could be described by the generalized partial credit IRT model. In the cross-validation analyses we found congruent mean scores for four different PROMs when the IRT based scoring procedures were used. CONCLUSIONS: We showed that the standardized physical function score metric developed in this study can be used to facilitate standardized reporting of physical function outcomes for ten commonly used make physical function PROMs.

Value of Biomarkers in the Prevention of Rheumatoid Arthritis.

Recent diagnostic advances allow to identify persons in a pre-symptomatic stage of rheumatoid arthritis (RA), opening the way for a preventive therapeutic intervention, which may potentially be curative. We review and discuss existing biomarkers predictive of future onset of RA. A responsible use of biomarkers in clinical settings will require an integration of blood-based tests, imaging techniques, clinical history, environmental risk factors, and family history.

Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study.

BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.

Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis.

OBJECTIVE: To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). METHODS: We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. RESULTS: We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001). CONCLUSION: Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.

The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries.

BACKGROUND: There are substantial differences in accessibility to biological disease modifying antirheumatic drugs (bDMARDs) across countries. The objective of this study was to analyse the impact of patient demographics, disease characteristics and gross domestic product (GDP) on abatacept (ABA) retention in patients with rheumatoid arthritis (RA) treated in clinical practice. METHODS: Data from nine European observational RA cohorts of patients treated with ABA were pooled. Kaplan-Meier analysis was used to compare drug retention across registries. Specific causes of drug retention were investigated using competing risks multivariate Cox regression. RESULTS: A total of 3961 patients treated with ABA, with 6188 patient-years of follow-up, were included. Patients in the different national registries had similar demographic features, but varied in baseline disease characteristics. ABA drug retention differed between countries, with median drug retention rates ranging from 1.2 to more than 6 years. The differences in drug retention were marginally explained by disparities in disease characteristics, while the national GDP per capita was strongly associated with drug retention (correlation coefficient -0.74; p=0.02). CONCLUSIONS: Patient characteristics at ABA initiation vary across Europe, probably reflecting differences in eligibility criteria and prescription patterns. However, the difference in ABA drug retention between countries was not primarily explained by disparities in patient characteristics. Lower ABA retention was observed in countries with a more liberal access to bDMARDs and higher GDP. National differences need to be accounted for when pooling data on treatment with bDMARDs from various countries.

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study.

OBJECTIVES: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. METHODS: SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. RESULTS: 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. CONCLUSIONS: These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

The new 2010 ACR/EULAR criteria as predictor of clinical and radiographic response in patients with early arthritis.

New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of rheumatoid arthritis (RA) have recently been proposed. The aim of this cohort study was to examine whether fulfilling these 2010 ACR/EULAR criteria at the first visit has an impact on the clinical course and on the radiographic progression of the disease. For this observational cohort study, we included patients from the Swiss RA registry SCQM with early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous disease modifying anti-rheumatic drugs (DMARDs). Patients were categorized into two groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria (≥6 points vs <6 points) at the first visit. The primary outcome measures were the evolution of the DAS 28 and of radiographic erosions as measured by the Ratingen score over time. Of the 592 patients fulfilling the inclusion criteria, 352 satisfied the 2010 ACR/EULAR criteria at baseline, whereas 240 were not classifiable as definite RA. The ACR/EULAR criteria scores correlated with disease activity at disease onset (R (2) = 0.31). DMARD treatment was subsequently initiated in all patients, mostly with methotrexate (MTX). There were no significant differences in the therapeutic strategies between patients fulfilling or not fulfilling the classification criteria. Six months after inclusion, patients fulfilling the ACR/EULAR criteria developed a 39.1 % reduction of DAS 28 scores, as compared to a 33.6 % reduction in patients not fulfilling the ACR/EULAR criteria (p = 0.0002), independently of their respective treatment strategy. Importantly, the DAS 28 scores were higher in those patients fulfilling the ACR/EULAR criteria (ACR/EULAR positive patients) throughout the observation, as compared to patients not fulfilling those (ACR/EULAR negative patients). Average radiographic progression was higher among ACR/EULAR positive than negative patients (progression of Ratingen score/year 0.50 vs 0.32, resp., p = 0.03) after 3 years of follow-up. Among early RA/UA patients, a score of the 2010 ACR/EULAR criteria sufficient to classify RA selects patients with worse clinical outcome and more radiographic progression.

Tocilizumab in the treatment of rheumatoid arthritis: a cost-effectiveness analysis in the UK.

BACKGROUND: Since receiving a positive recommendation in England, Wales and Scotland, tocilizumab (TCZ) is one of the options available to clinicians for the treatment of rheumatoid arthritis (RA) patients in the UK. OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of adding TCZ to the current treatment sequence of RA patients from a UK payer's perspective over a patient lifetime horizon. METHODS: An individual sampling model was developed to synthesise all clinical and economic inputs. Two scenarios were explored separately: patients contraindicated to methotrexate (MTX) and those MTX tolerant. For each scenario, the analysis compared three strategies. The standard of care (SoC) strategy included a sequence of the most commonly prescribed biologics; the other two comparator strategies considered the addition of TCZ to SoC at first line and second line. Patient characteristics were representative of UK patients. Treatment efficacy and quality-of-life evidence were synthesised from clinical trials and secondary sources. An analysis of a patient registry informed the model parameters regarding treatment discontinuation. The safety profile of all treatments in a given strategy was based on a network meta-analysis and literature review. Resource utilisation, treatment acquisition, administration, monitoring and adverse event treatment costs were considered. All costs reflect 2012 prices. Uncertainty in model parameters was explored by one-way and probabilistic sensitivity analysis. RESULTS: In the MTX-contraindicated population, if TCZ was added to the SoC in first line, the estimated incremental cost-effectiveness ratio (ICER) was £7,300 per quality-adjusted life-year (QALY) gained; if added in second line, the estimated ICER was £11,400 per QALY. In the MTX-tolerant population, the estimated costs and QALYs of the TCZ strategy were similar to those of the SoC strategy. Sensitivity analysis showed that parameters that affect the treatment cost (such as patient weight) can have a noticeable impact on the overall cost-effectiveness results. The majority of the other sensitivity analyses resulted in modest changes to the ICER. CONCLUSION: For the treatment of RA in MTX-tolerant and contraindicated patients, the addition of TCZ to the SoC was estimated to be a cost-effective strategy.

[Risk factors for the development of rheumatoid arthritis]. / Facteurs de risque pour le développement d'une polyarthrite rhumatoïde.

The role of genetic factors in the development rheumatoid arthritis (RA) is starting to be better understood. For patients to develop an autoimmunity associated with RA, an interaction between genetic risk factors and environmental risk factors seems to be required. In this paper, we will describe the putative role of a specific genetic risk factor and discuss several environmental risk factors, such as air pollution or specific infections, as well as behavioral factors such as smoking or specific foods. Ultimately, a better understanding of the gene-environment interactions leading to the development of autoimmunity will allow to identify people at high risk of developing RA, and perhaps to initiate preventive measures to avoid the disease of occurring all together.

[Cardiovascular complications in immune mediated diseases]. / Complications cardiovascu laires dans les maladies auto-immunes.

Immune mediated diseases carry an increased risk of major cardiovascular events (CV) and an increased risk of CV mortality. The increased CV risk appears to be linked directly to chronic inflammation. Various studies have demonstrated that reducing inflammation reduces the incidence of CV complications. We review the epidemiological evidence linking immune mediated diseases and increased CV risk, discuss the causal role of inflammation in the etiopathogenesis and appraise some potential benefits of specific anti-inflammatory therapies.

Adalimumab in acute sciatica reduces the long-term need for surgery: a 3-year follow-up of a randomised double-blind placebo-controlled trial.

INTRODUCTION: Two subcutaneous injections of adalimumab in severe acute sciatica significantly reduced the number of back operations in a short-term randomised controlled clinical trial. OBJECTIVE: To determine in a 3-year follow-up study whether the short-term benefit of adalimumab in sciatica is sustained over a longer period of time. METHODS: The primary outcome of this analysis was incident discectomy. Three years after randomisation, information on surgery could be retrieved in 56/61 patients (92%).A multivariate Cox proportional hazard models, adjusted for potential confounders, was used to determine factors predisposing to surgery. RESULTS: Twenty-three (41%) patients had back surgery within 3 years, 8/29 (28%) in the adalimumab group and 15/27 (56%) in the placebo group, p=0.04. Adalimumab injections reduced the need for back surgery by 61% (HR)=0.39 (95% CI 0.17 to 0.92). In a multivariate model, treatment with a tumour necrosis factor-α antagonist remained the strongest protective factor (HR=0.17, p=0.002). Other significant predictors of surgery were a good correlation between symptoms and MRI findings (HR=11.6, p=0.04), baseline intensity of leg pain (HR=1.3, p=0.06), intensity of back pain (HR=1.4, p=0.03) and duration of sickness leave (HR=1.01 per day, p=0.03). CONCLUSION: A short course of adalimumab in patients with severe acute sciatica significantly reduces the need for back surgery.

The effect of alcohol on radiographic progression in rheumatoid arthritis.

OBJECTIVE: Alcohol consumption reduces the risk of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis in animal models. It remains unknown whether alcohol consumption influences joint damage progression in RA. This study was undertaken to compare the rates of radiographic damage progression in alcohol drinkers and nondrinkers in a large prospective cohort of patients with RA. METHODS: All patients in the population-based Swiss Clinical Quality Management in RA registry database with at least 2 sequential radiographs were included. Joint erosions were assessed in 38 joints in the hands and feet using a validated scoring method. The rate of progression of erosions was analyzed using multivariate regression models for longitudinal data and was adjusted for potential confounders. RESULTS: The study included 2,908 patients with RA with a mean of 4 sequential radiographs and 3.9 years of followup. A trend toward reduced radiographic progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of 0.99% (95% confidence interval [95% CI] 0.89-1.09) and 1.13% (95% CI 1.01-1.26) at 1 year, respectively. Alcohol consumption displayed a J-shaped dose-response effect, with a more favorable evolution in occasional consumers (P = 0.01) and daily consumers (P = 0.001) as compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P = 0.0001). We found significant effect modification by sex, with male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86% [95% CI 0.70-1.03] versus 1.35% [95% CI 1.02-1.67]; P = 0.007). CONCLUSION: Our findings indicate a trend toward reduced radiographic progression in alcohol drinkers compared with nondrinkers, specifically in occasional and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less radiographic progression than do male nondrinkers.

Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in rheumatoid arthritis: a population-based study.

BACKGROUND: Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established. OBJECTIVE: To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA. METHODS: All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders. RESULTS: The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10-37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged. CONCLUSION: Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.

Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc.

STUDY DESIGN: Case-control study. OBJECTIVE: To determine whether inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8] are elevated in tissues intimately surrounding involved nerve roots of patients suffering from radiculopathy form herniated disc (HD). SUMMARY OF BACKGROUND DATA: Proinflammatory cytokines are postulated to play an important role in radiculopathy from HD. Although TNF-alpha has been found in human HD, it is not known whether TNF-alpha concentrations are increased in symptomatic patients. Epidural fat (EF) is another tissue in close contact with nerve roots. Histologic modifications of EF have been reported in patients with sciatica but concentrations of inflammatory cytokines have never been studied. METHODS: Twenty-three lumbar HD along with adjacent EF (EFHD) were harvested from patients with radicular syndrome. As controls, 14 intervertebral discs (IVDs) and 10 samples of EF (EFC) were obtained from patients without radicular syndrome undergoing spine surgery. Tissue explants were incubated ex vivo for 48 hours and the concentrations of cytokines were measured by elisa in the supernatants. Results were standardized according to tissue weight. RESULTS: All 4 cytokines were found at higher concentrations in EFHD compared with HD (P < 0.001). TNF-alpha was the only cytokine found in significantly higher levels in EFHD compared with EFC [median, interquartile range 6.6, (1.6-16.3) pg/mL per milligram of tissue vs. 2.3 (1.3-5.0), P < 0.05] and to subcutaneous fat [0.35 (0-2.28), P < 0.001]. No significant increase of either cytokines was found in HD compared with IVD. CONCLUSION: Higher concentrations of TNF-alpha were found in EF from patients with radiculopathy from HD compared with patients suffering from other type of back pain. These results support the role of TNF-alpha in the pathogenesis of radiculopathy from HD.

Cigarette smoking and radiographic progression in rheumatoid arthritis.

BACKGROUND: Smoking is a well-established environmental risk factor for the development of rheumatoid arthritis (RA). However, it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non-smokers over time. OBJECTIVE: To compare the rates of radiographic damage progression in current smokers and non-smokers in a large prospective RA cohort. METHODS: The SCQM-RA is a population-based registry monitoring disease activity, radiographic damage and symptoms at regular intervals. All patients in the SCQM-RA database with sequential plain radiographs were included. Joint erosions were assessed in 38 hand and foot joints with a validated scoring method. The rate of erosion progression was analysed using multivariate longitudinal regression models and adjusted for potential confounders. RESULTS: 2004 RA patients with a mean of 3.6 sequential radiographs and 3.1 years of follow-up were included. The 545 (27%) current smokers smoked on average 16 cigarettes per day and had a mean past smoking exposure of 20.6 pack-years. Radiographic joint damage progressed at a similar rate in current smokers and non-smokers (p = 0.26). However, smoking intensity was associated with a significant inverse dose-response; heavy smokers (>1 pack-day) progressed significantly less than non-smokers or moderate smokers (p<0.001). CONCLUSION: Radiographic joint damage progressed at an equivalent rate in smokers and non-smokers. Furthermore, a significant trend was observed for reduced radiographic progression and generally more favourable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progression.