The clinical picture of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria: Is this still the same disease?

Objective

To examine the implications of using the new classification criteria for rheumatoid arthritis (RA) in clinical practice in a cohort of patients with very early arthritis.

Methods

The study group comprised 301 disease‐modifying antirheumatic drug–naive patients with early arthritis. The baseline diagnosis was assessed by applying the 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria for RA as well as established diagnostic criteria for other rheumatic diseases. Diagnostic and prognostic data were collected after 2 years of followup. Fulfillment of the 2010 ACR/EULAR criteria was evaluated in the subset of patients in whom undifferentiated arthritis (UA) was diagnosed when the 1987 ACR criteria were applied, and fulfillment of RA criteria over time was tested by applying the 2 different criteria sets.

Results

The median arthritis duration at baseline was 4 months (range 0–12 months). At baseline, 28% of the patients fulfilled the 1987 ACR criteria, and 45% fulfilled the 2010 ACR/EULAR criteria for RA. Among the patients classified as having UA at baseline according to the 1987 ACR criteria, 36% had fulfilled the 2010 ACR/EULAR criteria already at baseline. Among the patients classified as having UA at baseline but who fulfilled the 1987 ACR criteria after 2 years of followup, 85% had fulfilled the 2010 ACR/EULAR criteria at baseline. Patients with early disease who fulfilled the 2010 ACR/EULAR criteria were less likely to be autoantibody positive and more likely to have monarthritis at presentation than those fulfilling the 1987 ACR criteria.

Conclusion

Use of the 2010 ACR/EULAR criteria clearly allows earlier diagnosis of RA, although the clinical picture is slightly different on the group level, and RA may be falsely diagnosed in some patients with self‐limiting disease.

     

Ultrasound Can Improve the Accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis to Predict the Requirement for Methotrexate Treatment

Objective

The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) refer to a possible use of ultrasound “for confirmation of the clinical findings.” We undertook this study to determine the optimized definition of ultrasound‐detected synovitis for the 2010 ACR/EULAR criteria and to assess the impact of its use on the accuracy of RA classification.

Methods

One hundred nine patients with musculoskeletal symptoms for ≤3 years were enrolled in the study. Patients underwent clinical, laboratory, radiographic, and comprehensive ultrasonographic assessments at baseline and received routine management from expert rheumatologists who were blinded to the ultrasound findings.

Results

Sensitivity and specificity of the 2010 ACR/EULAR criteria using different definitions of synovitis to identify patients who developed a disease requiring methotrexate (MTX) treatment within 1 year were 58.5% and 79.4%, respectively, for clinical synovitis (tenderness or swelling), 78.0% and 79.4%, respectively, for ultrasound‐detected synovitis with a gray‐scale (GS) imaging score ≥1 (GS ≥1 ultrasound synovitis), and 56.1% and 93.7%, respectively, for GS ≥2 ultrasound synovitis or a synovial power Doppler (PD) signal score ≥1 (GS ≥2/PD ≥1 ultrasound synovitis). Receiver operating characteristic curve analysis for the criteria scores revealed the largest area under the curve with GS ≥2/PD ≥1 ultrasound synovitis.

Conclusion

Ultrasound assessment improves the accuracy of the 2010 ACR/EULAR criteria for identifying patients with a disease requiring MTX treatment. Our data provide preliminary but vital information for the methodology to confirm the presence of synovitis using ultrasound in the 2010 ACR/EULAR criteria.

     

Pilot study to assess the frequency of fibromyalgia, depression, and sleep disorders in patients with granulomatosis with polyangiitis (Wegener's)

Objective

To assess the frequency of fibromyalgia syndrome (FMS), depression, and sleep disorders in patients with granulomatosis with polyangiitis (Wegener's) (GPA).

Methods

The London Fibromyalgia Epidemiologic Study Screening Questionnaire (LFESSQ), Symptom Intensity Scale, Epworth Sleepiness Scale (ESS), and the Brief Patient Health Questionnaire‐9 (BPHQ‐9) were administered prospectively to patients who met the American College of Rheumatology criteria for GPA. Fatigue was captured quantitatively by the fatigue visual analog scale (VAS) and qualitatively by the LFESSQ fatigue questionnaire. Disease activity and damage were captured by using the Birmingham Vasculitis Activity Score for GPA (BVAS/GPA) and the Vasculitis Damage Index (VDI). Frequency of FMS and depression in GPA was compared with the general population.

Results

Patients with GPA have significantly greater frequency of FMS (LFESSQ 23.6 versus 13; P = 0.02) and depression (22% versus 7.6%; P < 0.001) than the general population. Twenty‐nine percent of GPA patients had sleep abnormalities according to ESS scores of ≥10; 76.4% reported fatigue and 49.1% indicated that fatigue significantly limited their activities. There was no correlation between BPHQ‐9, ESS, LFESSQ, fatigue VAS, and VDI, BVAS/GPA, or disease duration. There was a strong correlation between fatigue VAS and BPHQ‐9 (r = 0.73; 95% confidence interval [95% CI] 0.54, 0.92). The correlation between fatigue VAS and ESS was significant but not as strong as with the BPHQ‐9 (r = 0.36; 95% CI 0.10, 0.62).

Conclusion

FMS and depression occur more often in GPA compared with the general population. The association is not related to disease activity, damage, or disease duration. Fatigue is very common and significantly limits normal daily activities. Depression and sleep disorders contribute to fatigue in GPA patients.     

Polyarteritis nodosa in Croatian children: a retrospective study over the last 20 years

To analyze the disease characteristics, treatment modalities and outcome of polyarteritis nodosa (PAN) in Croatian children. Cross-sectional study included all children with PAN diagnosed according to EULAR/PRES/PRINTO criteria during the last two decades. PAN was diagnosed in 12 patients (6 girls and 6 boys) mean age (±SD) 11.33 ± 3.08 years. The share of PAN among all vasculitides was 3.8 %. Systemic PAN was diagnosed in 7 children (58 %), microscopic polyangiitis in 3 (25 %), cutaneous PAN in 2 (17 %). The most consistent symptoms were skin involvement (90 %) and arthritis/arthralgia (60 %). The CNS was affected in 33 % of patients. Inflammatory markers (C-reactive protein and erythrocyte sedimentation rate [ESR]) were elevated in all patients, and anti-neutrophil cytoplasmatic antibodies were positive in all patients with microscopic polyangiitis. Therapy mode for all patients was corticosteroids. Immunosuppressive drugs were used as additional therapy for patients with severe symptoms. Two patients (17 %), both suffering from microscopic polyangiitis, died due to renal failure during the follow-up. In comparison with available studies, we found a difference in distribution of childhood polyarteritis nodosa as well as some clinical characteristics (e.g., higher prevalence of neurological and pulmonary symptoms), while other researched features, laboratory and treatment were similar.     

Predictors and persistence of new-onset clinical remission in rheumatoid arthritis patients

Objective

To determine the prevalence and persistence of new-onset clinical remission in rheumatoid arthritis (RA) patients.

Methods

The Consortium of Rheumatology Researchers of North America (CORRONA) cohort was used to examine the prevalence of remission and associated comorbidities and RA therapies according to the 2011 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria. Factors influencing the likelihood of remaining in remission were identified by logistic regression with generalized estimating equations. Analysis of variance and Tukey's test were used to determine differences in disability according to whether RA patients had been in remission or only low disease activity (LDA).

Results

A total of 2105 individuals met ACR/EULAR remission criteria at the most recent visit within CORRONA, yielding an 8% point prevalence of remission. Patients with certain comorbidities (e.g., heart failure) were significantly less likely to achieve or remain in remission compared to those without these conditions (p < 0.001 for each). Among prednisone users, the prevalence of remission was 1–6% (depending on dose) higher compared to those not on prednisone (10%). More than 50% of patients who had consistently been in remission for ≥1 year were able to remain in remission over the next year. Patients consistently in remission had less disability than patients who achieved LDA or who fluctuated between remission and LDA.

Conclusion

Patients consistently in remission for at least 1 year had a high likelihood to remain in remission. These individuals might be considered the most likely candidates for de-escalation or withdrawal of RA treatments.     

Excessive interleukin‐15 transpresentation endows NKG2D+CD4+ T cells with innate‐like capacity to lyse vascular endothelium in granulomatosis with polyangiitis (Wegener's)

Objective

Granulomatosis with polyangiitis (Wegener's) (GPA) is a rare systemic vasculitis of unknown etiology. Contribution of T cell–mediated immunity is suggested by the presence of granulomatous inflammation and T cell infiltrates in different tissues. We undertook this study to determine whether CD4+ T cells aberrantly expressing the NKG2D activating receptor might participate in the pathophysiology of the disease.

Methods

We performed a detailed phenotype and functional analysis of CD4+ T cells in a cohort of 90 GPA patients (37 with localized GPA and 53 with generalized GPA) in comparison with 39 age‐matched controls.

Results

We observed circulating innate‐like CD4+ T cells expressing an assortment of activating natural killer (NK) cell receptors (NKG2D, 2B4, DNAX‐associated molecule 1, and some killer cell Ig‐like receptors) and their signaling partners. Expansions of NKG2D+CD4+ T cells greater than a critical threshold of 3% yielded 100% specificity for generalized vasculitis versus localized granulomatosis, suggesting their participation in endothelium damage. Excessive interleukin‐15 (IL‐15) transpresentation through increased expression of IL‐15 receptor α (IL‐15Rα), together with abnormal expression of major histocompatibility complex (MHC) class I chain–related A protein on monocyte/macrophages, induced abnormal expansion of NKG2D+CD4+ T cells. These cells were primed in vivo to exert direct, MHC‐independent cytotoxicity toward microvascular endothelial cells expressing the cognate ligands of NK cell receptors.

Conclusion

Our results suggest that NK cell–like CD4+ T cells might be the driving force of the vasculitis in GPA, and point to IL‐15 as an important mediator in the progression of GPA toward generalized vasculitis. IL‐15/IL‐15Rα antagonists may thus become novel therapeutic tools to decrease the pool of NK cell receptor–positive CD4+ T cells in selected GPA patients.

     

Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood‐onset systemic lupus erythematosus

Objective

To prospectively validate the provisional criteria for the evaluation of response to therapy in children with systemic lupus erythematosus (SLE).

Methods

In this multicenter study, childhood‐onset SLE patients (n = 98; 81 girls, 17 boys, 50% white, 88% non‐Hispanic) were followed every 3 months for up to 7 visits (total number of visits 623). The 5 childhood‐onset SLE core response variables were obtained at the time of each visit: 1) physician assessment of overall disease activity, 2) parent assessment of patient well‐being, 3) Child Health Questionnaire, 4) proteinuria, and 5) global disease activity measure score, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). Physician‐rated relevant changes in the disease course (clinically relevant improvement, no change in disease, or worsening) between visits served as the criterion standard. Mixed models were used to assess the diagnostic accuracy of the 4 highest‐ranked provisional definitions of response to therapy.

Results

There were 89 episodes of clinically relevant improvement between 2 consecutive visits, and 448 episodes without improvement. Irrespective of the choice of the global disease activity measure (ECLAM, SLAM, SLEDAI), sensitivities of all 4 highest‐ranked definitions were low (all ≤31%), whereas their specificities were excellent (all >88%). Using logistic models, alternative definitions can be developed with both 80% sensitivity and specificity.

Conclusion

The provisional criteria of response to therapy in childhood‐onset SLE may have considerably lower sensitivity than previously reported. Additional validation in clinical trials is necessary to further evaluate the measurement properties of the provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology criteria for response to therapy in children with SLE.     

Implementation of a treat‐to‐target strategy in very early rheumatoid arthritis: Results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study

Objective

Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat‐to‐target strategy aimed at achieving remission in very early RA in daily clinical practice.

Methods

Five hundred thirty‐four patients with a clinical diagnosis of very early RA were included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Treatment adjustments were based on the Disease Activity Score in 28 joints (DAS28), aiming at a DAS28 of <2.6 (methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with biologic agents in case of persistent disease activity). The primary outcome was disease activity after 6 months and 12 months of followup, according to the DAS28, the European League Against Rheumatism (EULAR) response criteria, and the modified American College of Rheumatology (ACR) remission criteria. Secondary outcomes were time to first DAS28 remission and outcome of radiography.

Results

Six‐month and 12‐month followup data were available for 491 and 389 patients, respectively. At 6 months, 47.0% of patients achieved DAS28 remission, 57.6% had a good EULAR response, and 32.0% satisfied the ACR remission criteria. At 12 months, 58.1% of patients achieved DAS28 remission, 67.9% had a good EULAR response, and 46.4% achieved ACR remission. The median time to first remission was 25.3 weeks (interquartile range 13.0–52.0). The majority of patients did not have clinically relevant radiographic progression after 1 year.

Conclusion

The successful implementation of this treat‐to‐target strategy aiming at remission demonstrated that achieving remission in daily clinical practice is a realistic goal.

     

Rituximab or a second anti–tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti–tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register

Objective

To compare the effectiveness of rituximab (RTX) or a second anti–tumor necrosis factor (anti‐TNF) therapy in rheumatoid arthritis (RA) patients who had failed their first anti‐TNF and switched to either RTX or a second anti‐TNF, in routine clinical practice.

Methods

RA patients were registered with the British Society for Rheumatology Biologics Register. Response to treatment 6 months after switching was assessed using European League Against Rheumatism (EULAR) criteria and improvements in a Health Assessment Questionnaire (HAQ) score (0.22 unit or more). Regression analyses were used to compare EULAR response and improvement in HAQ score between the 2 groups, adjusting for propensity scores.

Results

In total, 1,328 patients were included in the analysis of EULAR response, and 937 patients were included in the analysis of HAQ scores. Six months after switching, 54.8% of patients who switched to RTX were EULAR responders compared to 47.3% of those who switched to a second anti‐TNF. A total of 38.4% of RTX patients achieved a clinically important improvement in HAQ score compared to 29.6% in anti‐TNF patients. After adjustment using propensity scores, patients who switched to RTX were significantly more likely to achieve EULAR response (odds ratio [OR] 1.31; 95% confidence interval [95% CI] 1.02, 1.69) compared to those who switched to an alternative anti‐TNF. RTX patients were also significantly more likely to achieve improvements in HAQ score (OR 1.49; 95% CI 1.07, 2.08).

Conclusion

The results suggest that switching to RTX may be of more benefit than switching to an alternative anti‐TNF therapy after failing the first anti‐TNF therapy in RA patients.     

BVAS version 3 and BVAS/GPA: standing on the same line?

Clinical Rheumatology - Birmingham vasculitis activity score (BVAS) version 3 (BVAS 3.0) and BVAS/granulomatosis with polyangiitis (BVAS/GPA) are used as indicators of disease activity in...     

Kawasaki disease and juvenile systemic lupus erythematosus

Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD.     

Comparison of long‐term clinical outcome with etanercept treatment and adalimumab treatment of rheumatoid arthritis with respect to immunogenicity

Objective

To compare rates of sustained low and minimal disease activity and remission according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria during 3‐year followup in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care.

Methods

Four hundred seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n = 203) or adalimumab (n = 204) and assessed at 3‐ and later 6‐month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters were measured at each time point, as were anti‐adalimumab antibodies in adalimumab‐treated patients. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (28‐joint Disease Activity Score [DAS28] <3.2), minimal disease activity (DAS28 <2.6), or ACR/EULAR remission based on the Simplified Disease Activity Index (SDAI). Non‐overlapping response rates were calculated.

Results

Among the adalimumab group, 13% reached sustained low disease activity but not sustained minimal disease activity, 15% reached sustained minimal disease activity but not sustained remission according to the SDAI, and 16% reached sustained ACR/EULAR remission. In the etanercept group the corresponding rates were 16%, 11%, and 12%, respectively (P = 0.42, overall test for linear trend). Adalimumab‐treated patients without anti‐adalimumab antibodies (n = 150 [74%]) had the best outcomes, and adalimumab‐treated patients with anti‐adalimumab antibodies the worst, with outcomes in etanercept‐treated patients in between (P < 0.0001). Differences were most apparent in the sustained SDAI remission and sustained minimal disease activity categories. For example, 40% of anti‐adalimumab antibody–negative patients, 23% of etanercept‐treated patients, and 4% of anti‐adalimumab antibody–positive patients achieved at least sustained minimal disease activity.

Conclusion

Overall, etanercept and adalimumab treatment appear similar in inducing a good long‐term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of anti‐adalimumab antibodies.

     

Granulomatosis with Polyangiitis in Childhood

Granulomatosis with polyangiitis (GPA) is a rare yet frequently organ- or life-threatening systemic vasculitis affecting small- to medium-sized arteries in multiple organs. It characteristically leads to alveolar hemorrhage and destructive, pauci-immune glomerulonephritis. GPA is also characterized by granulomas in the upper and lower respiratory tract causing erosive sinusitis and nodular or even cavitating lesions in the respiratory tract. Antineutrophil cytoplasmic antibodies, a hallmark of GPA, are likely integral to the pathogenesis and recently have become a therapeutic target. International collaborations in childhood vasculitis have led to the development and validation of childhood vasculitis classification criteria, advanced our understanding of the clinical phenotype at presentation of GPA, and improved our ability to capture disease activity and determine treatment choices. Treatment efficacy and safety data continue to be largely derived from adult GPA studies. This review focuses on the recent publications on epidemiology, pathogenesis, and treatment in childhood GPA and relevant publications from the adult GPA literature.     

Fcγ receptor type IIIA genotype and response to tumor necrosis factor α–blocking agents in patients with rheumatoid arthritis

Objective

To determine whether a functional single‐nucleotide polymorphism in the gene encoding Fcγ receptor type IIIA (FcγRIIIA) correlates with the response to treatment with tumor necrosis factor α inhibitors in rheumatoid arthritis (RA).

Methods

The study population comprised 282 Swedish patients with RA in whom the therapeutic efficacy of conventional disease‐modifying antirheumatic drugs had been insufficient. Infliximab or etanercept treatment was initiated, and patients were evaluated after 3 months, using the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 or the European League Against Rheumatism (EULAR) criteria. The chi‐square test was used to compare response rates across FcγRIIIA genotypes.

Results

No differences in genotype distribution were observed among nonresponders compared with ACR20 responders (P = 0.80), ACR50 responders (P = 0.56), or ACR70 responders (P = 0.91). Similar results were observed when analyzing infliximab and etanercept separately or when using the EULAR response criteria.

Conclusion

Unlike the findings of a previous study, the results of the current study suggest that the 158V/F polymorphism of FcγRIIIA is very unlikely to influence the clinical efficacy of infliximab or etanercept in patients with RA.

     

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

Objective

To evaluate response to therapy over a 24‐month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM).

Methods

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.

Results

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.

Conclusion

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.

     

Ofatumumab,a human anti‐CD20 monoclonal antibody,for treatment of rheumatoid arthritis with an inadequate response to one or more disease‐modifying antirheumatic drugs: Results of a randomized,double‐blind,placebo‐controlled,phase I/II study

Objective

To investigate the safety and efficacy of ofatumumab, a novel human anti‐CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease‐modifying antirheumatic drug.

Methods

This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated.

Results

AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24.

Conclusion

Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.

     

Development and validation of the european league against rheumatism response criteria for rheumatoid arthritis: Comparison with the preliminary american college of rheumatology and the world health organization/international league against rheumatism criteria

Objective. To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WHO)/International League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA). Methods. EULAR response criteria were developed combining change from baseline and level of disease activity attained during followup. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity. Results. EULAR response criteria had good construct, criterion, and discriminant validity. ACR and WHO/ILAR criteria showed only good criterion validity. Conclusion. EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA.