Higher Baseline Disease Activity Research Articles

Determining the Lowest Optimally Effective Methotrexate Dose for Individual RA Patients Using Their Dose Response Relation in a Tight Control Treatment Approach.

ObjectiveTo determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted.MethodsData from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment strategy in early RA was used. For each patient a curve for disease activity over time was fitted and the MTX dose after which further step-up did not result in relevant improvement in disease activity anymore was determined the 'lowest optimally effective MTX dose (LOED)'. The association of demographic and clinical characteristics at baseline with this LOED and with the level of disease activity reached at LOED was studied.ResultsIn 204 (100 MTX and 104 MTX with prednisone) out of 236 patients LOED could be defined. 10 mg/wk was the most prevalent LOED in patients treated with MTX and prednisone and 10 mg/wk, 20 mg/wk and 30 mg/wk in the MTX strategy. Although the specific LOED could not reliably be predicted, higher baseline disease activity, height and lower weight were associated with higher LOEDs (i.e at least 15 mg/wk). A score was presented to decide on a starting dose of 10 mg/wk or (at least) 15 mg/wk. The level of disease activity at LOED could not be reliably predicted.ConclusionA starting dose of 10 mg/wk might be a good choice for most patients and is frequently already the optimal dose. However, a subgroup of patient can be determined who would require higher MTX doses.

Drug-specific risk, and associated factors, of vasculitis-like events in patients exposed to tumour necrosis factor alpha inhibitor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

BackgroundThe association between TNF inhibitors and vasculitis-like events, possibly secondary to induction of autoantibodies, has been well reported. However, the incidence, drug-specific differences, and associated factors have been poorly characterised. The aim of this study was to assess the drug-specific risk, and associated factors, of vasculitis-like events in patients with rheumatoid arthritis treated with TNF inhibitors and non-biologic disease modifying antirheumatic drugs (nbDMARDs). MethodsThis analysis included two cohorts from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) recruited from Oct 1, 2001, to May 31, 2015: patients starting first TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) and a comparison cohort receiving nbDMARDs. After identification of vasculitis-like events, additional information from hospital consultants was sought for verification. The risk of an event was compared between the two cohorts with Cox proportional hazard models, adjusted using propensity scores (inverse probability of treatment weighting). FindingsThere were 95 incident vasculitis-like events (14 in 3640 patients on nbDMARD, 81 in 12 745 patients starting first TNF inhibitors) with 20 365 and 52 428 patient-years of follow-up generating crude incidence rates of 7 per 10 000 and 16 per 10 000 person-years, respectively. After adjustment, the hazard ratio (HR) of vasculitis-like events in patients on TNF inhibitors versus nbDMARD was 1·3 (95% CI 0·4–4·0). Drug specific HRs were highest in patients on infliximab (HR 2·7, 95% CI 1·4–5·2) and etanercept (2·6, 1·4–4·8), but these associations were not significant after adjustment. Factors associated with vasculitis-like events included baseline disease activity (HR 1·4, 95% CI 1·2–1·7), rheumatoid factor positive status (1·8, 1·2–2·8), health assessment questionnaire score (1·7, 1·2–2·3), and sulfasalazine use (0·6, 0·3–0·9). InterpretationIn one of the largest registers of patients receiving biological drugs, the absolute risk of vasculitis-like events was low, irrespective of whether patients received TNF inhibitors or nbDMARDs. There were no significant differences in risk between TNF inhibitors after adjustment. Higher baseline disease activity and seropositive status were associated with higher rates of vasculitis events, whereas baseline sulfasalazine use was associated with lower rates. To our knowledge, this is the first study to date to assess the risk of this outcome in a prospective, observational cohort. FundingMedical Research Council.

Erosions in the foot at baseline are predictive of orthopaedic shoe use after 10 years of treat to target therapy in patients with recent onset rheumatoid arthritis

The objective of this study is to investigate if foot joint damage due to rheumatoid arthritis (RA) can predict whether patients will start wearing orthopaedic shoes (OS) within 10 years after treatment start. Data from recent onset RA patients with 10 years follow-up from the BeSt (Dutch acronym for treatment strategies) study were used. Treatment was tightly controlled, targeted at disease activity score (DAS) ≤2.4, according to 1 of 4 pre-specified treatment strategies. After 10 years of follow-up, orthopaedic shoe use was recorded in 285/508 patients (responders to questionnaires at 10 years). Between-group differences for orthopaedic shoe users and non-users were calculated at baseline, after 10 years, and change scores over the 10-year period were calculated. Predictors for orthopaedic shoe use were identified by univariable and multivariable logistic regression analyses. Orthopaedic shoe use was reported by 57/285 patients after 10 years. Orthopaedic shoe users had more joint damage, joint swelling and pain in the feet already at baseline and after 10 years. At both time points, DAS of orthopaedic shoe users and non-users was similar. Multivariable logistic regression showed that dichotomized foot erosions score (cut-off ≥1 erosion) (OR 2.42), anti-citrullinated protein antibodies (ACPA) (OR 4.64) and DAS (OR 1.77) were independent predictors of orthopaedic shoe use. Despite intensive targeted treatment, 57/285 recent onset RA patients started using orthopaedic shoes over 10 year of follow-up. Presence of foot erosions at treatment start predicts orthopaedic shoe use after 10 years. The risk of orthopedic shoe use increased for ACPA-positive patients and for those with higher baseline disease activity.Electronic supplementary materialThe online version of this article (doi:10.1007/s10067-015-3145-1) contains supplementary material, which is available to authorized users.

Prevention of joint destruction in patients with high disease activity or high C-reactive protein levels: Post hoc analysis of the GO-FORTH study

Objectives: To assess the influence of golimumab dosage and disease activity on joint destruction in patients with active rheumatoid arthritis (RA) in the GO-FORTH study.Methods: Efficacy was compared among groups given basal methotrexate plus placebo, golimumab (50 mg), or golimumab (100 mg) with stratification by high (HDA) or moderate (MDA) baseline disease activity and by high or low baseline C-reactive protein (CRP).Results: Among HDA or high CRP patients, the mean change of the total Sharp score was 3.48 and 3.41 in the placebo group, 1.94 and 2.71 in the 50 mg group, and 0.39 and 1.15 in the 100 mg group, respectively. The percentage of progression-free patients with HDA or high CRP was 40.4% and 40.0%, 43.1% and 38.2%, and 69.8% and 61.5%, respectively. Among MDA or low CRP patients, both golimumab doses showed similar prevention of joint destruction. Among HDA or high CRP patients, a shorter disease duration and higher TSS/disease duration ratio were associated with joint destruction.Conclusion: Both doses of golimumab (50 or 100 mg) prevented joint destruction in MDA or low CRP patients, but 100 mg was better for HDA or high CRP patients with a shorter disease duration or higher TSS/disease duration ratio.

Effectiveness and survival-on-drug of certolizumab pegol in rheumatoid arthritis in clinical practice: results from the national Swedish register

Objectives: Evidence regarding the efficacy and effectiveness of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients who have failed to respond to treatment with a tumour necrosis factor inhibitor (TNFi) is limited. The aim of this study was to describe the effectiveness and survival-on-drug of CZP in a real-life setting, both in TNFi-naïve patients and in patients who had previously failed TNFis, and in relation to disease activity at baseline.Method: The national Swedish Rheumatology Quality Register (SRQ) was used to identify patients with RA starting treatment with CZP between 2009 and 2013. The effectiveness of treatment was assessed using the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), measures of remission, the European League Against Rheumatism (EULAR) response during 0–6 months from start of treatment, and survival-on-drug during the first 30 months.Results: A total of 945 RA patients started treatment with CZP. Of these, 540 (57.1%) received CZP as the first biological treatment, 215 (23%) had failed one previous TNFi, and 190 (20%) had failed at least two TNFis. Overall, 71% achieved at least a EULAR moderate response and 38% had a EULAR good response at 6 months from baseline. TNFi-naïve patients achieved significantly better results and had better survival-on-drug compared to patients who had failed previous TNFis. Around 20% of patients who had not responded to two or more prior TNFis achieved EULAR good response to therapy and a similar percentage achieved remission. Patients who had high baseline disease activity had a higher risk of discontinuing treatment compared to those without high disease activity.Conclusions: In this real-life RA cohort, CZP was associated with significant clinical improvement. The effectiveness and survival-on-drug vary markedly depending on the line of treatment.

Prevalence, incidence and characteristics of the metabolic syndrome (MetS) in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs: the complex relationship between MetS and disease activity.

IntroductionA higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity.MethodsThe study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m2 was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level.ResultsUp to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01).Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS.RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission.ConclusionsMetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study

Background: It is unclear whether natalizumab and fingolimod have analogous efficacy for relapsing-remitting multiple sclerosis (RRMS). Objective: To compare the outcome of RRMS patients treated with either therapy. Methods: RRMS patients treated with natalizumab or fingolimod at Verona Hospital, Italy, were included. The study design was retrospective, based on prospectively collected clinical and MRI data. As efficacy outcomes, time to relapse, relapse rate, expanded disability status scale (EDSS) score change, and new T2/gadolinium-enhancing lesions on brain MRI were compared over treatment period between the two groups. Multivariate Cox and logistic regression models were used to control for potential confounders. Results: Fifty-seven subjects receiving natalizumab and 30 receiving fingolimod for a median duration of 23 (1-63) and 22 (2-35) months, respectively (p = 0.22) were included. Patients treated with natalizumab had a more active pre-treatment disease course compared to those treated with fingolimod. In multivariate analysis, the relapse risk was reduced in patients on natalizumab (Hazard Ratio = 0.33; 95% CI = 0.11-1.03; p = 0.056) compared to those on fingolimod. There was no significant difference in EDSS and MRI outcomes. No relevant unexpected adverse events occurred. One patient discontinued natalizumab for progressive multifocal leukoencephalopathy. Conclusions: RRMS patients receiving natalizumab had higher baseline disease activity and lower relapse risk over 20 months of treatment compared to those receiving fingolimod. Head-to-head randomized clinical trials are needed.

Importance of methotrexate therapy concomitant with tocilizumab treatment in achieving better clinical outcomes for rheumatoid arthritis patients with high disease activity: an observational cohort study.

The purpose of this study was to identify the effects of concomitant use of MTX and baseline characteristics for remission in the treatment of RA with tocilizumab (TCZ) in daily clinical practice. A total of 240 RA patients who received TCZ were selected from the multicentre Tsurumai Biologics Communication Registry. Predictive baseline factors for remission [28-item DAS (DAS28) < 2.6] at 52 weeks were determined by logistic regression analysis. To confirm whether the associations varied by the level of baseline disease activity, we also assessed the model including the interaction term (each baseline variable × DAS28). In total, 49.3% of the study participants used MTX with TCZ. Even after controlling for the baseline DAS28, shorter disease duration (≤3 year) [odds ratio (OR) 3.58 (95% CI 1.81, 7.07)], less structural damage [Steinbroker stage ≤II, OR 2.33 (95% CI 1.32, 4.12)] and concomitant prednisolone use [OR 0.38 (95% CI 0.21, 0.68)] showed significant predictive values for remission. Concomitant MTX use failed to show a significant association with remission, whereas a significant interaction was observed among concomitant MTX use × DAS28 (P = 0.006). In patients with high baseline disease activity (DAS28 > 5.1), concomitant MTX use was associated with increased odds for remission [adjusted OR for all baseline variables 2.54 (95% CI 1.11, 5.83)], while no association was indicated between them in patients with low to moderate baseline disease activity (DAS28 ≤ 5.1). Concomitant MTX use is an important component of TCZ treatment for RA patients with high disease activity.

Is Swollen to Tender Joint Count Ratio a New and Useful Clinical Marker for Biologic Drug Response in Rheumatoid Arthritis? Results From a Swedish Cohort

To study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. Patients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 ≤ STR ≤ 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. A total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. STR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.

FRI0543 Is baseline disease activity associated with 1-year health care costs & productivity losses after biologic treatment start in patients with ra?

BackgroundLittle is known about the cost trajectory in patients starting biologics with moderate disease activity.ObjectivesTo compare 1-year health care costs and productivity losses after initiation of first biologic treatment in...

AB0389 Number of cardiovascular risk factors may be associated with higher disease activity severity. Exploratory analysis of baseline data from the canadian MTX and etanercept outcome study: a randomized trial of etanercept and MTX vs etanercept alone in RA

ObjectivesThis ongoing real-world rheumatoid arthritis (RA) non-inferiority trial compared the proportion of patients with low disease activity while on etanercept (ETN) monotherapy vs ETN + methotrexate (MTX). Baseline data were...

AB0281 Remission rates during golimumab treatment for rheumatoid arthritis are associated with differences in baseline disease states across geographic regions in the go-more study

BackgroundRegional differences in practice patterns and access to biologic treatment for rheumatoid arthritis (RA) may lead to regional differences in baseline disease characteristics, which could influence response to biologic treatments.ObjectivesTo...

THU0178 Comprehensive Disease Control with Golimumab in Patients with Rheumatoid Arthritis

BackgroundComprehensive management of rheumatoid arthritis (RA) involves clinical goals such as remission and low disease activity (LDA) and outcomes important to patients such as daily functioning and minimization of pain.ObjectivesTo...

Predicting future response to certolizumab pegol in rheumatoid arthritis patients: Features at 12 weeks associated with low disease activity at 1 year

To determine the prognostic significance of data collected early after starting certolizumab pegol (CZP) to predict low disease activity (LDA) at week 52. Data from 703 CZP-treated patients in the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) trial through week 12 were used as variables to predict LDA (Disease Activity Score in 28 joints-erythrocyte sedimentation rate ≤3.2) at week 52. We identified variables, developed prediction models using classification trees, and tested performance using training and testing data sets. Additional prediction models were constructed using the Clinical Disease Activity Index (CDAI) and an alternate outcome definition (composite of LDA or American College of Rheumatology criteria for 50% improvement [ACR50]). Using week 6 and 12 data and across several different prediction models, response (LDA) and nonresponse at 1 year were predicted with relatively high accuracy (70-90%) for most patients. The best performing model predicting nonresponse by 12 weeks was 90% accurate and applied to 46% of the population. Model accuracy for predicted responders (30% of the RAPID 1 population) was 74%. The area under the receiver operating curve was 0.76. Depending on the desired certainty of prediction at 12 weeks, ~12-25% of patients required >12 weeks of treatment to be accurately classified. CDAI-based models and those evaluating the composite outcome (LDA or ACR50) achieved comparable accuracy. We could accurately predict within 12 weeks of starting CZP whether most established rheumatoid arthritis (RA) patients with high baseline disease activity would likely achieve/not achieve LDA at 1 year. Decision trees may be useful to guide prospective management for RA patients treated with CZP and other biologics.

Reduction in Healthcare and Societal Resource Utilization Associated with Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a common, chronic, neurodegenerative condition associated with substantial healthcare and societal economic burden. Disease-modifying MS treatments have the potential to reduce health resource utilization (HRU), thereby reducing the attendant socioeconomic burden. This study aimed to compare health and societal resource use and productivity in patients with relapsing-remitting MS (RRMS) receiving cladribine tablets versus placebo over 96 weeks in the CLARITY study. The CLARITY study was a 96-week, randomized, double-blind, placebo-controlled study in patients with RRMS. HRU data, societal resource use and productivity data were collected at baseline and during scheduled patient visits, at 6-month intervals. The recall period for the HRU questionnaire was 3 months. The study was carried out at 155 sites across 32 countries worldwide. The intent-to-treat population comprised 1326 patients with RRMS randomized to cladribine 3.5 mg/kg (n = 433) or 5.25 mg/kg (n = 456) tablets or placebo (n = 437). Patient subgroups with high baseline disease activity were identified based on criteria of ≥2 relapses in the previous year (n = 392); ≥1 T1 gadolinium-enhancing (Gd+) lesion (n = 413); and ≥2 relapses in the previous year plus ≥1 T1 Gd+ lesion (n = 138). Cladribine tablets were administered in two (3.5 mg/kg group) or four (5.25 mg/kg group) short courses given at 4-week intervals at the start of a 48-week treatment period, followed by another two courses at the start of a subsequent 48-week re-treatment period. Interferon-β rescue therapy was permitted from week 24. Intravenous corticosteroids were available for the treatment of neurological relapses. HRU outcomes included mean number of hospital days and emergency room (ER), clinic and home visits during each study period. Societal resource use and productivity outcomes included mean number of hours and days of paid assistance, mean patient and carer work days missed, and self-reported productivity. The mean number of hospital days per patient over 96 weeks was lower in the cladribine tablets groups (3.5 mg/kg group: -3.19 days; 5.25 mg/kg group: -1.54 days [both p < 0.01]) versus placebo. Likewise the mean number of ER visits was lower in both cladribine tablet groups compared with placebo (3.5 mg/kg group: -0.09 visits; 5.25 mg/kg group: -0.11 visits [both p < 0.01]), and the mean number of clinic visits was also lower in both cladribine tablet groups (3.5 mg/kg group: -0.68 visits; 5.25 mg/kg group: -0.66 visits [both p = 0.01]). Furthermore, treatment with cladribine tablets was associated with reduced mean numbers of missed work days for patients (3.5 mg/kg group: -2.42 days [p < 0.01]; 5.25 mg/kg group: -0.60 days [p = 0.50]). Corticosteroid use was lower amongst patients in the cladribine tablet groups than in the placebo group. The reduction in hospital days following treatment with cladribine tablets was also observed in patients with high disease activity at study baseline. This study provides evidence that the efficacy of cladribine tablets observed during the CLARITY study was associated with a reduced consumption of healthcare resources and a decreased need for medical and societal support. ClinicalTrials.gov identifier: NCT00213135; EudraCT number: 2004-005148-28.

Therapeutic approaches in the treatment of juvenile dermatomyositis in patients with recent-onset disease and in those experiencing disease flare: An international multicenter PRINTO study

To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24 months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported "as observed" and in the intent-to-treat (ITT) population. Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the "as observed" analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare (P<0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively (P<0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease.

Therapeutic approaches for the treatment of new onset and flared juvenile systemic lupus erythematosus with active renal disease: an international multicenter PRINTO study

Results New patients had higher baseline disease activity compared to flared patients, but initiated corticosteroids at similar doses. Cyclophosphamide was the most common (41.2%; 99/240) immunosuppressive medication, followed by azathioprine (25%; 60/240). Mycophenolate mofetil and azathioprine were more commonly used in flared patients. Patients from Latin America received more pulses and higher doses of steroids when compared to Western Europe. The use of cyclophosphamide was similar in all 4 regions. In the “as observed” analysis 78% (103/132) of new compared to 57.4% (58/101) of flared JSLE patients (p=0.0007) reached at least PRINTO/ACR 70 level of response at 6 months, which increased to 87.1% in new and 77.2% in flared patients at month 24 (p=0.12). Corresponding figures for the ITT analysis were similar and 80% (68/85) of new vs 73.7% (42/57) of flared patients were able to maintain the initial assigned therapy over 24 months (p=0.38). Corticosteroids were discontinued in 28.6% (20/143).

What is the outcome of RA in 2011 and can we predict it?

There are secular trends in improvement in disease activity and X-ray damage at baseline and cross-sectionally in prevalent cases of rheumatoid arthritis (RA) in recent years. These changes should translate into improved physical function and mortality, but evidence for this is lacking, perhaps because the mean age at RA diagnosis and of prevalent cases is increasing, mainly as a consequence of demographic changes. This trend is accompanied by an increasing prevalence of co-morbidities, in particular cardiovascular and respiratory disease. The higher prevalence of smoking, diabetes and physical inactivity in RA cases contributes to the burden of co-morbidity. Predictors of poorer treatment response and thus a worse prognosis include female gender, being a smoker, autoantibody positivity, high baseline disease activity and co-morbidities such as depression. There is a need for better understanding of predictors of treatment response to guide the right choice of therapy and thus improve outcome further.

Phase II study of tofacitinib (CP‐690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate

To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib (CP-690,550) with placebo in Japanese patients with active rheumatoid arthritis (RA) receiving stable background methotrexate (MTX) who had an inadequate response to MTX alone. A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in this 12-week, phase II, double-blind study. All patients remained on background MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. ACR20 response rates at week 12 were significant (P < 0.0001) for all tofacitinib treatment groups: 1 mg twice a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a day, 80.8% versus placebo, 14.3%. A significant dose-response relationship for the ACR20 was observed (P < 0.0001). Low disease activity was achieved by 72.7% of patients with high baseline disease activity for tofacitinib 10 mg twice a day at week 12 (P < 0.0001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, and Disease Activity Score 28-3 (C-reactive protein) were also reported. The most commonly reported adverse events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or moderate in severity. Serious AEs were reported by 5 patients. No deaths occurred. In Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was efficacious and had a manageable safety profile.

Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registry

A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. One hundred thirty-six patients received treatment for SLE. The mean +/- SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 +/- 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA-SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE.