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ABSTRACT: This review examines the literature on the frequency of remission associated with different treatment approaches in early rheumatoid arthritis (ERA). Trials reporting remission outcomes were identified through searches of the CINAHL, EMBASE, and Medline (PubMed) databases from 2000 through August 2012. Additional literature was identified through hand searching. The proportion of patients achieving remission and/or radiographic non-progression was extracted from each study. Evidence was examined in the context of unified remission criteria and practical considerations for achieving and maintaining remission are discussed. The literature highlights the benefits of early treatment with disease-modifying anti-rheumatic drug (DMARD) combination therapy, combination therapy with a biologic, and tight control with a pre-specified treatment target in achieving remission in ERA. The added stringency of the 2011 remission criteria may increase the proportion of patients achieving true remission, while identifying predictors of sustained remission may also help patients achieve better radiographic and functional outcomes.
Clinical and experimental rheumatology 04/2013; · 2.15 Impact Factor
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Nature Reviews Rheumatology 02/2013; 9(3):137-8. · 8.39 Impact Factor
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ABSTRACT: OBJECTIVE: In inflammatory arthritis, rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe clinical outcomes. Our objective was to determine whether ACPA and RF remain stable in early inflammatory arthritis and whether their trajectories over time or baseline levels predicted clinical outcomes. METHODS: The study population consisted of patients enrolled in the Canadian Early Arthritis Cohort Study with baseline and at least 12-month followup values of RF and ACPA. Primary outcomes were Disease Activity Score (DAS) remission and the presence of erosions at 12 and 24 months. Other objectives included swollen joint count, Health Assessment Questionnaire score, and DAS. RESULTS: At baseline, 225/342 (66%) patients were ACPA-positive and 334/520 (64%) were RF-positive. At 24 months, 15/181 (8%) ACPA-positive patients became negative. A larger number of patients changed from ACPA-negative to positive: 13/123 (11%). For RF, fluctuations were more common: 67/240 (28%) reverted from positive to negative and 21/136 (18%) converted from negative to positive. RF and ACPA fluctuations did not predict disease outcomes. Patients who remained ACPA-positive throughout followup were more likely to have erosive disease (OR 3.86, 95% CI 1.68, 8.92). CONCLUSION: RF and ACPA have the potential to revert and convert during the early course of disease. Fluctuations in RF and ACPA were not associated with clinical outcomes.
The Journal of Rheumatology 02/2013; · 3.69 Impact Factor
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ABSTRACT: OBJECTIVES: Evaluation of long-term safety of rituximab in rheumatoid arthritis (RA). METHODS: Pooled observed case analysis of data from patients with moderate-to-severe, active RA treated with rituximab in a global clinical trial programme. RESULTS: As of September 2010, 3194 patients had received up to 17 rituximab courses over 9.5 years (11 962 patient-years). Of these, 627 had >5 years' follow-up (4418 patient-years). A pooled placebo population (n=818) (placebo+methotrexate (MTX)) was also analysed. Serious adverse event and infection rates generally remained stable over time and multiple courses. The overall serious infection event (SIE) rate was 3.94/100 patient-years (3.26/100 patient-years in patients observed for >5 years) and was comparable with placebo+MTX (3.79/100 patient-years). Serious opportunistic infections were rare. Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin (Ig)M and 3.5% (n=112) low IgG levels for ≥4 months after ≥1 course. SIE rates were similar before and during/after development of low Ig levels; however, in patients with low IgG, rates were higher than in patients who never developed low IgG. Rates of myocardial infarction and stroke were consistent with rates in the general RA population. No increased risk of malignancy over time was observed. CONCLUSIONS: This analysis demonstrates that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience. Overall, the findings indicate that there was no evidence of an increased safety risk or increased reporting rates of any types of adverse events with prolonged exposure to rituximab during the 9.5 years of observation.
Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTXrandomized groups. RESULTS: A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21). CONCLUSION: RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.
The Journal of Rheumatology 10/2012; · 3.69 Impact Factor
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ABSTRACT: OBJECTIVE: To determine the factors most strongly associated with an increase in therapy of early rheumatoid arthritis (ERA). METHODS: Data from the Canadian Early Arthritis Cohort (CATCH) were included if the patient had ≥ 2 visits and baseline and 6 months data. A regression analysis was done to determine factors associated with treatment intensification. RESULTS: Of 1145 patients with ERA, 790 met inclusion criteria; mean age was 53.4 years (SD 14.7), mean disease duration 6.1 months (SD 2.8), 75% were female, baseline Disease Activity Score-28 (DAS28) was 4.7 (SD 1.8) and 2.9 (SD 1.8) at 6 months for included patients. Univariate factors for intensifying treatment were physician global assessment (MDGA; OR 7.8 and OR 7.4 at 3 and 6 months, respectively, p < 0.0005), swollen joint count (SJC; OR 4.7 and OR 7.3 at 3 and 6 months, p < 0.0005), and DAS28 (OR 3.0 and OR 4.6 at 3 and 6 months, p < 0.0005). In the regression model only MDGA was strongly associated with treatment intensification (OR 1.5 and OR 1.2 at 3 and 6 months, p < 0.0005); DAS28 was not consistently predictive (OR 1.0, p = 0.987, and OR 1.2, p = 0.023, at 3 and 6 months). DAS28 was the reason for treatment intensification 2.3% of the time, compared to 51.7% for SJC, 49.9% for tender joint count, and 23.8% for MDGA. For the same SJC, larger joint involvement was more likely to influence treatment than small joints at 3 months (OR 1.4, p = 0.027). CONCLUSION: MDGA was strongly associated with an increase in treatment at 3 and 6 months in ERA, whereas DAS28 was not. Physicians rarely stated that DAS28 was the reason for increasing treatment.
The Journal of Rheumatology 09/2012; · 3.69 Impact Factor
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ABSTRACT: OBJECTIVES: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. METHODS: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. RESULTS: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores. CONCLUSIONS: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.
Annals of the rheumatic diseases 08/2012; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: Our objective was to describe characteristics of Canadian patients with early arthritis and examine differences between those fulfilling 1987 and 2010 rheumatoid arthritis (RA) classification criteria. METHODS: The Canadian Early Arthritis Cohort (CATCH) is a national, multicenter, observational, prospective cohort of patients with early inflammatory arthritis, receiving usual care, recruited since 2007. Inclusion criteria include age > 16 years; symptom duration 6-52 weeks; swelling of ≥ 2 joints or ≥ 1 metacarpophalangeal/proximal interphalangeal joint; and 1 of rheumatoid factor ≥ 20 IU, positive anticitrullinated protein antibodies (ACPA), morning stiffness ≥ 45 min, response to nonsteroidal antiinflammatory drug, or positive metatarsophalangeal joint squeeze test. Data from patients enrolled to March 15, 2011, were analyzed. RESULTS: In total, 1450 patients met the eligibility criteria (1187 were followed). At baseline, mean age was 53 ± 15 years, symptom duration was 6.1 ± 3.2 months, Disease Activity Score (DAS28) was 4.9 ± 1.6, Health Assessment Questionnaire-Disability Index was 1.0 ± 0.7. Forty-one percent (n = 450) of patients had moderate (3.2 < DAS28 ≤ 5.1) and 46% (n = 505) had high (DAS28 > 5.1) disease activity; 28% of those with baseline radiographs (n = 250/908) had radiographic evidence of erosions. ACPA status was available for 70% (n = 831) of patients; 55% (n = 453) tested positive. Sixty percent (n = 718) of patients were treated with methotrexate (MTX) initially. Of 612 patients without erosions, 63% and 83% fulfilled 1987 and 2010 RA classification criteria, respectively. Seventy-three percent (n = 166) of those who did not fulfill 1987 criteria were newly identified by the 2010 criteria. These patients had less severe disease and more were MTX-naive compared to those satisfying the 1987 criteria. Forty-seven percent of all patients achieved remission at 1 year. CONCLUSION: Patients with early RA present with moderate high disease activity; < 50% achieve remission at 1 year, despite MTX treatment in the majority. The 2010 RA classification criteria identify more patients with RA who would previously have been designated as having undifferentiated disease. However, these patients have lower disease activity at the time of identification.
The Journal of Rheumatology 08/2012; · 3.69 Impact Factor
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Rheumatology (Oxford, England) 07/2012; 51 Suppl 5:v1-2. · 4.24 Impact Factor
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Rheumatology (Oxford, England) 07/2012; 51 Suppl 5:v55-6. · 4.24 Impact Factor
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ABSTRACT: RA is defined by the interrelated triad of disease activity, joint damage and disability. Although disease activity and its associated disability are reversible, joint damage and its associated disability are not. Thus, an important goal of RA therapy is to maximally reduce disease activity and thereby mitigate the accumulation of irreversible joint damage. Treatment for patients with RA should be initiated early and aggressively, with frequent assessments and a goal of achieving remission as quickly as possible after treatment initiation. We propose a treatment algorithm that recommends early and aggressive therapy with high-dose MTX therapy (15-25 mg/week), which may include moderate doses of glucocorticoids. The goal is to achieve low disease activity (determined by a composite measure that includes joint counts) within 3-6 months. If low disease activity is not achieved by 6 months, another conventional DMARD or a biologic agent should be added to the treatment regimen or patients should be switched to another DMARD plus a glucocorticoid. Once low disease activity is achieved, the treatment goal for the ensuing 3-6 months becomes disease remission.
Rheumatology (Oxford, England) 07/2012; 51 Suppl 5:v48-54. · 4.24 Impact Factor
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Edward C Keystone,
Bernard Combe,
Josef Smolen,
Vibeke Strand,
Niti Goel,
Ronald van Vollenhoven,
Philip Mease,
Robert Landewé,
Roy Fleischmann,
Kristel Luijtens,
Désirée van der Heijde
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ABSTRACT: To evaluate the safety and efficacy of 2-year administration of certolizumab pegol (CZP) + MTX in patients with active RA.
Patients completing 52 weeks in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 1 trial (52-week completers), or withdrawing at week 16 due to lack of ACR20 response were eligible for open-label treatment (CZP 400 mg every other week + MTX). After 2 years' treatment, HAQ-Disability Index response, ACR20/50/70 responses, DAS-28 and radiographic progression were assessed in 52-week completers. ACR20/50/70 and DAS-28 were also calculated for the intent-to-treat (ITT) population. Adverse events were assessed in patients who received one or more CZP doses during the study.
At week 100, 88.9% (n = 216) of 52-week completers who originally received CZP 200 mg + MTX and open-label treatment remained in the study. In this group, ACR20/50/70 at week 100 were 68.2, 55.2 and 35.6%, respectively. HAQ-DI and DAS-28 improvements were sustained throughout the open-label extension (mean change -0.79 and -3.5 at week 100, respectively). A total of 46.7% (n = 113) of CZP 200 mg + MTX 52-week completers achieved low disease activity by week 100. Inhibition of radiographic progression was maintained. Similar findings were observed in 52-week completers who originally received CZP 400 mg + MTX and in the ITT population. Rates of serious infection or malignancies did not increase over time and no new safety signals were observed.
CZP + MTX provided sustained, 2-year inhibition of radiographic progression and sustained improvements in RA clinical signs and symptoms, with no new safety signals observed in patients who completed 2 years of treatment. Trial registration: clinicaltrials.gov, http://www.clinicaltrials.gov, NCT00175877.
Rheumatology (Oxford, England) 05/2012; 51(9):1628-38. · 4.24 Impact Factor
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Désirée van der Heijde, Edward C Keystone,
Jeffrey R Curtis,
Robert B Landewé,
Michael H Schiff,
Dinesh Khanna,
Tore K Kvien,
Lucian Ionescu,
Leon M Gervitz,
Owen R Davies,
Kristel Luijtens,
Daniel E Furst
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ABSTRACT: To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis.
In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks.
Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse - 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 - and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively).
Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).
The Journal of Rheumatology 05/2012; 39(7):1326-33. · 3.69 Impact Factor
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Emily McKeown,
Vivian P Bykerk,
Faye De Leon,
Ashley Bonner,
Carter Thorne,
Carol A Hitchon,
Gilles Boire,
Boulos Haraoui,
Diane S Ferland, Edward C Keystone,
Janet E Pope
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ABSTRACT: To characterize steroid use and compliance with glucocorticoid-induced osteoporosis (GIOP) guidelines within a large early inflammatory arthritis cohort.
Using the Canadian Early Arthritis Cohort (CATCH) database, patients with inflammatory arthritis on glucocorticoids (oral, IA and i.m.) were identified. Consecutive steroid exposure was defined as using glucocorticoids for two consecutive clinic visits (at least 90 days apart). The primary outcome was the proportion of patients receiving calcium, vitamin D and a bisphosphonate among patients treated with consecutive oral glucocorticoids.
Six hundred and fifty-five patients were in the CATCH database, where 273 patients were identified as glucocorticoid users, of whom 48% were on oral prednisone, 38% received i.m. or IA and 13% both. The median oral daily dose of prednisone was 5 mg (interquartile range 2.5-10). Consecutive users (CUs, n = 78) compared with non-consecutive users (NUs, n = 532) showed that CUs were older (56 vs 50 years, P = 0.001); females were fewer (63% vs 74%, P = 0.04), but a similar proportion were RF positive (51% in CU vs 56% in NU, P = 0.73). For the primary outcome, rates of prophylaxis for users of consecutive oral steroids were as follows: 53% were treated with calcium, 47% with vitamin D and 25% were on a bisphosphonate. For users of oral prednisone at doses ≥7.5 mg/day, rates of prophylaxis were as follows: 64% were treated with calcium, 57% with vitamin D and 21% were on a bisphosphonate.
Glucocorticoid therapy is frequently used in early inflammatory arthritis. The use of calcium, vitamin D or a bisphosphonate was low among chronic glucocorticoid users and illustrates the need for more diligence in patients receiving glucocorticoids to prevent GIOP.
Rheumatology (Oxford, England) 04/2012; 51(9):1662-9. · 4.24 Impact Factor
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ABSTRACT: To describe the frequency of remission in an early rheumatoid arthritis (ERA) cohort.
The frequency of remission was evaluated, based on 8 definitions including the Boolean-based American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria.
Of 369 patients, remission at 12 months ranged from 18% according to the ACR/EULAR clinical trial criteria to 40% according to the 28-joint Disease Activity Score (DAS28) < 2.6. Higher tender joint count, swollen joint count, and physician global scores were seen for DAS28-based definitions, and patient global assessment (PtGA) scores were almost 5-fold higher for DAS28 remission.
Remission is achievable in ERA but its frequency differs according to the remission definition applied. Adoption of the new ACR/EULAR definition will limit the number classified as in remission, especially if the PtGA criteria are rated high for reasons other than inflammatory arthritis.
The Journal of Rheumatology 04/2012; 39(6):1155-8. · 3.69 Impact Factor
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ABSTRACT: To evaluate the effect of golimumab on physical function, general health, and fatigue in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.
In the multicenter, randomized, placebo-controlled GO-FORWARD study, 444 adults with active RA despite MTX received subcutaneous placebo + MTX (crossover to golimumab 50 mg at Week 24), golimumab 100 mg + placebo, golimumab 50 mg + MTX, or golimumab 100 mg + MTX every 4 weeks. Physical function and general health were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical and Mental Component Summary (PCS, MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36), respectively, through Week 52. Fatigue was measured through Week 24 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire.
Mean improvements from baseline in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Weeks 14 and 24) were significantly greater for golimumab 50 mg + MTX and 100 mg + MTX versus placebo + MTX. Significantly greater proportions of patients treated with golimumab + MTX achieved clinically meaningful improvements from baseline to Weeks 14 and 24 in HAQ-DI, PCS, and FACIT-Fatigue scores. Mean improvements in SF-36 PCS (Week 14), MCS (Week 24), and FACIT-Fatigue (Weeks 14 and 24) scores were significantly greater for golimumab 100 mg + placebo versus placebo + MTX. Mean improvements from baseline in HAQ-DI, SF-36 PCS, and MCS scores through Week 24 were sustained through Week 52.
Patients with active RA despite MTX had significant improvement in physical function, general health, and fatigue following golimumab + MTX therapy; improvements in physical function and general health were maintained through Week 52. (Clinical Trials Registration NCT00264550).
The Journal of Rheumatology 04/2012; 39(6):1185-91. · 3.69 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemokines, proteinases and adhesion molecules, making them key players in the RA disease process. If proteins are not correctly folded, cellular stress occurs that can be relieved in part by increased degradation of the aberrant proteins by the proteasome or autophagy. We hypothesized that the activity of the protein degradation pathways would be increased in response to TNFα stimulation in RA synovial fibroblasts compared with control fibroblasts.
Endoplasmic reticulum (ER) stress markers were examined in synovial fibroblasts by immunoblotting and PCR. Use of the autophagy and proteasome protein degradation pathways in response to TNFα stimulation was determined using a combination of experiments involving chemical inhibition of the autophagy or proteasome pathways followed by immunoblotting for the autophagy marker LC3, measurement of proteasome activity and long-lived protein degradation, and determination of cellular viability.
RA synovial fibroblasts are under acute ER stress, and the stress is increased in the presence of TNFα. Autophagy is the main pathway used to relieve the ER stress in unstimulated fibroblasts, and both autophagy and the proteasome are more active in RA synovial fibroblasts compared with control fibroblasts. In response to TNFα, the autophagy pathway but not the proteasome is consistently stimulated, yet there is an increased dependence on the proteasome for cell viability. If autophagy is blocked in the presence of TNFα, an increase in proteasome activity occurs in RA synovial fibroblasts but not in control cells.
TNFα stimulation of synovial fibroblasts results in increased expression of ER stress markers. Survival of synovial fibroblasts is dependent on continuous removal of proteins by both the lysosome/autophagy and ubiquitin/proteasome protein degradation pathways. Both pathways are more active in RA synovial fibroblasts compared with control fibroblasts. These results may provide a better understanding of the mechanism of TNFα on prolonging the survival of synovial fibroblasts in RA tissue.
Arthritis research & therapy 03/2012; 14(2):R62. · 4.27 Impact Factor
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Paul Emery,
Roy Fleischmann,
Désirée van der Heijde, Edward C Keystone,
Mark C Genovese,
Philip G Conaghan,
Elizabeth C Hsia,
Weichun Xu,
Anna Baratelle,
Anna Beutler,
Mahboob U Rahman
Arthritis & Rheumatism 01/2012; · 7.87 Impact Factor
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ABSTRACT: This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA).
Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events.
A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated.
This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA.
NCT00649545.
BMC Musculoskeletal Disorders 11/2011; 12:261. · 1.58 Impact Factor
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Paul Emery,
Désirée van der Heijde,
Mikkel Ostergaard,
Philip G Conaghan,
Mark C Genovese, Edward C Keystone,
Roy Fleischmann,
Elizabeth C Hsia,
Weichun Xu,
Stephen Xu,
Mahboob U Rahman
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ABSTRACT: Evaluate relationships between MRI and clinical/laboratory/radiographic findings in rheumatoid arthritis (RA).
637 methotrexate-naive patients (GO-BEFORE) and 444 patients with active RA despite methotrexate (GO-FORWARD) were randomly assigned to subcutaneous placebo + methotrexate, golimumab 100mg + placebo, golimumab 50mg + methotrexate, or golimumab 100mg + methotrexate every-4-weeks. In GO-BEFORE(n=318) and GO-FORWARD(n=240) substudies, MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis, bone oedema and bone erosion (RA MRI scoring (RAMRIS) system). Relationships between RAMRIS scores and serum C-reactive protein (CRP), 28-joint count disease activity score (DAS28-CRP) and van der Heijde modified Sharp (vdH-S) scores were assessed.
Baseline and weeks 24/28 DAS28-CRP, CRP, and vdH-S generally correlated well with baseline and week 24 RAMRIS synovitis, oedema and erosion scores. Early (week 4) CRP changes correlated with later (week 12) RAMRIS synovitis/oedema change scores; earlier (week 12) changes in some RAMRIS scores correlated with later (weeks 24/28) changes in vdH-S. Significant correlations between RAMRIS change scores and clinical/radiographic change scores were weak.
MRI and clinical/laboratory/radiographic measures generally correlated well. Associations between earlier changes in CRP and later changes in RAMRIS synovitis/osteitis were observed. Changes in MRI and clinical/radiographic measures did not correlate well, probably because MRI is more sensitive than radiographs and more objective than DAS28-CRP.
Annals of the rheumatic diseases 09/2011; 70(12):2126-30. · 8.11 Impact Factor
