Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately treated rheumatoid arthritis

OBJECTIVES: Fatigue is an important systemic symptom of rheumatoid arthritis (RA) but has rarely been evaluated consistently after initiation of treatment in RA patients. This study examined the effects of adalimumab (HUMIRA, Abbott Laboratories, Abbott Park, IL, USA), a fully human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody, on reducing fatigue in patients with RA. METHODS: A total of 1526 patients with RA were enrolled in 3 randomized, placebo-controlled clinical trials of adalimumab versus placebo plus methotrexate (MTX) or placebo plus standard antirheumatic therapies. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale questionnaire (which has been validated in RA) at baseline, mid-study, and at the end of the study. Logistic regression models were constructed using baseline demographic variables to test for treatment effect. In addition, sensitivity analyses were performed to determine the robustness of the data. RESULTS: At baseline in the 3 trials, patients' fatigue ranged from 27.9-29.7, representing considerable fatigue on the FACIT fatigue scale. Fatigue was significantly and consistently reduced in adalimumab-treated patients in the 3 clinical trials. Relative to placebo plus MTX, the adalimumab 40-mg-every-other-week dosage group reported statistically significantly less fatigue at all time points post-baseline. Improvements between adalimumab and placebo ranged from 3-7 points across all 3 trials, with a 3-4-point change representing a minimum clinically important difference. CONCLUSION: Adalimumab treatment was shown to significantly reduce fatigue in patients with moderate to severe RA. Changes in fatigue in all 3 trials were found to be clinically important.     

Effect of recombinant human erythropoietin and intravenous iron on anemia and disease activity in rheumatoid arthritis.

OBJECTIVE: To investigate whether treatment of anemia of chronic disease (ACD) in patients with rheumatoid arthritis (RA) with recombinant human erythropoietin (rHu-Epo) in combination with intravenous (i.v.) iron influences health related quality of life (HRQoL) and clinical outcome including disease activity. METHODS: Thirty patients with ACD and RA were treated with 150 IU/kg rHu-Epo twice weekly for 12 weeks. As well, in case of functional iron deficiency 200 mg of iron-sucrose per week was given intravenously. Vitality and fatigue as dimensions of HRQoL were evaluated by the vitality subscale of the Short Form-36 (SF-36-VT) and the Multidimensional Assessment of Fatigue (MAF). Muscle strength was measured by the Muscle Strength Index. RESULTS: All 28 patients completing the study responded to treatment; 23/28 patients developed functional iron deficiency and received i.v. iron (mean absolute dose 710 +/- 560 mg). Average hemoglobin concentration increased from 10.7 +/- 1.1 to 13.2 +/- 1.0 g/dl after a mean treatment period of 8.7 +/- 2.3 weeks. Muscle strength increased from 43.5 +/- 11.2 to 49.1 +/- 12.9 and SF-36-VT from 28.2% +/- 14.3% to 47.1% +/- 20.8%. while fatigue decreased (MAF from 34.7 +/- 9.3 to 25.0 +/- 11.3). Among the disease activity variables the number of swollen/tender joints, erythrocyte sedimentation rate, Disease Activity Score, and RA Disease Activity Index improved significantly during treatment. CONCLUSION: Treatment of ACD in RA patients with rHu-Epo and i.v. iron is safe and effective in correction of anemia, increases muscle strength. improves vitality, and lowers fatigue. In addition we observed a reduction of disease activity.     

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed

OBJECTIVE: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). RESULTS: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05). CONCLUSION: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.     

Rituximab for rheumatoid arthritis refractory to anti–tumor necrosis factor therapy: Results of a multicenter,randomized, double‐blind,placebo‐controlled,phase III trial evaluating primary efficacy and safety at twenty‐four weeks

Objective

To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti–tumor necrosis factor (anti‐TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population.

Methods

We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long‐Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2‐year, multicenter, randomized, double‐blind, placebo‐controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti‐TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF‐36) instruments, as well as Genant‐modified Sharp radiographic scores at 24 weeks.

Results

Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab‐treated patients than placebo‐treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate‐to‐good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab‐treated patients, who also had clinically meaningful improvements in fatigue, disability, and health‐related quality of life (demonstrated by FACIT‐F, HAQ DI, and SF‐36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild‐to‐moderate severity. The rate of serious infections was 5.2 per 100 patient‐years in the rituximab group and 3.7 per 100 patient‐years in the placebo group.

Conclusion

At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti‐TNF therapies.

     

Adalimumab improves joint-related and skin-related functional impairment in patients with psoriatic arthritis: patient-reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial

OBJECTIVE: To evaluate the effects of adalimumab on patient-reported outcomes of joint-related and skin-related functional impairment, health-related quality of life, fatigue and pain in patients with psoriatic arthritis (PsA). METHODS: Patients with moderately- to severely- active PsA were treated with adalimumab, 40 mg, every other week, or placebo, in this 24-week, randomised, controlled trial. Patient-reported outcomes included the Health Assessment Questionnaire Disability Index (HAQ DI), Short-Form 36 Health Survey (SF-36), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale and the Dermatology Life Quality Index (DLQI). RESULTS: Adalimumab (n = 151) and placebo (n = 162) groups were comparable with respect to baseline demographics and disease severity. Significant changes from baseline in HAQ DI were reported for adalimumab v placebo (-0.4 v -0.1, p<0.001) at both 12 and 24 weeks. At week 24, significant improvements in the SF-36 domains of physical functioning, role-physical, bodily pain, general health, vitality and social functioning, as well as the physical component summary score, were observed for adalimumab versus placebo (p<0.01). These reported changes in HAQ DI and SF-36 were also clinically important. Significantly more patients treated with adalimumab had complete resolution of functional loss (HAQ DI = 0) and dermatological-related functional limitations (DLQI = 0) compared with placebo at weeks 12 and 24 (p< or =0.001). Adalimumab led to significantly greater improvements in FACIT-Fatigue scores, pain scores, and disease activity measures versus placebo at 12 and 24 weeks (p<0.001 for all). CONCLUSIONS: Adalimumab improved physical-related and dermatological-related functional limitations, HRQOL, fatigue and pain in patients with PsA treated for 24 weeks.     

Minimal clinically important difference for 7 measures of fatigue in patients with systemic lupus erythematosus

OBJECTIVE: To determine the minimal clinically important difference (MCID) for 7 measures of fatigue in patients with systemic lupus erythematosus (SLE). METHODS: Study subjects completed 7 fatigue instruments [Fatigue Severity Scale (FSS), Multidimensional Assessment of Fatigue (MAF), Multidimensional Fatigue Inventory (MFI), Vitality scale of the MOS-SF-36, Chalder Fatigue Scale (CFS), Functional Assessment of Chronic Illness Therapy-Fatigue, and a global Rating Scale (RS)] and then participated in a series of interviews with other study participants comparing their fatigue with one another. Each interview participant rated the difference in their fatigue levels on a 7-point transition scale. The MCID was estimated from the mean difference in fatigue scores between each pair of interview participants based on their subjective rating of fatigue contrast. The MCID was also estimated using linear regression modeling. RESULTS: Eighty patients with SLE participated. Patients reported significant levels of fatigue [mean normalized (0 = none, 100 = maximum) fatigue scores for the 7 instruments ranged from 49.8 (CFS) to 71.1 (FSS)]. The MCID of "a little more" fatigue tended to be greater than the MCID for a "little less fatigue" and differed significantly for FSS and MAF. The MCID of normalized scores estimated by linear regression ranged from 7.0 (CFS) to 14.3 (MFI). CONCLUSION: Fatigue is a common and debilitating component of SLE. Estimates of MCID will help to interpret changes observed in a fatigue score and will be critical in estimating sample size requirements for clinical trials including fatigue as an outcome.     

Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study

OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p相似文献   

Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks

OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab-treated patients, who also had clinically meaningful improvements in fatigue, disability, and health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity. The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group. CONCLUSION: At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.     

A randomized,double‐blind,placebo‐controlled,phase III study of the human anti‐tumor necrosis factor antibody adalimumab administered as subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate

Objective: Adalimumab is a fully human, monoclonal, antitumour necrosis factor antibody approved for the treatment of rheumatoid arthritis (RA) in more than 60 countries. We investigated the efficacy and safety of 40 mg every‐other‐week (eow) subcutaneous injections of adalimumab with methotrexate (MTX) versus placebo with MTX in Korean patients with RA with insufficient responses to MTX. Methods: This was a 24‐week, randomized, double‐blind, placebo‐controlled, phase III study conducted at six sites in Korea. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Secondary endpoints included ACR50, ACR70, and individual ACR components. Beginning at week 18, non‐responders (< 20% reduction in swollen and tender joint counts) could switch to rescue therapy with open‐label adalimumab 40 mg eow. Results: Of the 128 patients enrolled, 65 received adalimumab and 63 received placebo. An ACR20 response at week 24 was achieved by 61.5% of patients receiving adalimumab versus 36.5% receiving placebo (P < 0.01). ACR50 and ACR70 responses were achieved by 43.1% and 21.5% of adalimumab patients versus 14.3% and 7.9% of placebo patients (P < 0.001 and P < 0.05, respectively). Adalimumab significantly improved all seven ACR core components. Statistically significant improvements in ACR20 were observed with adalimumab as early as week 2. Adalimumab was generally well tolerated; there were no significant differences in incidences of adverse events between groups. Conclusions: In Korean patients with RA with insufficient responses to MTX, combination therapy with adalimumab and MTX was more efficacious than placebo and MTX in reducing RA signs and symptoms.     

Measuring fatigue in rheumatoid arthritis: a systematic review of scales in use

OBJECTIVE: Fatigue is an important outcome for patients with rheumatoid arthritis (RA). The purpose of this study was to identify the scales being used to measure RA fatigue, and to systematically examine the evidence for their validation. METHODS: Articles measuring fatigue in RA were sought using the terms RA and fatigue, and RA and tiredness, plus scale, questionnaire, inventory, and checklist. Index articles reporting identifiable RA fatigue data were examined for the fatigue scale used. Index and validation articles for each scale were reviewed for evidence supporting scale validation to measure RA fatigue using a standardized checklist of content, face, criterion, and construct validity, reliability, and sensitivity to change. RESULTS: A total of 61 index articles used 23 different fatigue scales to measure RA fatigue on 71 occasions. Seventeen scales had either no data on validation in RA or limited evidence. Reasonable evidence of validation was identified for 6 scales, each also having some evidence of sensitivity to change: ordinal scales, the Short Form 36 vitality subscale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, visual analog scales (VAS), the Profile of Mood States, and the RA-specific Multidimensional Assessment of Fatigue scale (MAF). However, the 4 generic scales would benefit from further validation in patients with RA, the VAS requires standardization, and the MAF would benefit from further sensitivity data. CONCLUSION: It was possible to identify evidence of reasonable validation for 6 of 23 scales being used to measure RA fatigue. Researchers and clinicians should select scales to measure RA fatigue carefully.     

Adalimumab reduces pain, fatigue, and stiffness in patients with ankylosing spondylitis: results from the adalimumab trial evaluating long-term safety and efficacy for ankylosing spondylitis (ATLAS)

OBJECTIVE: To evaluate the effect of adalimumab on pain, fatigue, and stiffness in patients with active ankylosing spondylitis (AS). METHODS: The Adalimumab Trial Evaluating Long-Term Safety and Efficacy for Ankylosing Spondylitis (ATLAS) was an ongoing 5-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period. Patients were randomized to adalimumab 40 mg or placebo by subcutaneous injection every other week. Pain was assessed by the bodily pain domain scores of the Medical Outcomes Study Short Form-36 Health Survey (SF-36) and also by total back pain and nocturnal pain using visual analog scales. Fatigue was measured by the SF-36 vitality domain and question 1 of the Bath AS Disease Activity Index (BASDAI). Morning stiffness was measured by the mean of BASDAI questions 5 and 6. RESULTS: Of 315 patients enrolled, 208 received adalimumab 40 mg and 107 received placebo. At Week 12, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the SF-36 bodily pain score (p < 0.001), total back pain score (p < 0.001), nocturnal pain score (p < 0.001), fatigue (p < 0.01), and morning stiffness (p < 0.001). Pain, fatigue, and morning stiffness were significantly correlated (p < 0.001) with baseline values of patient-reported health-related quality of life (HRQOL), and physical function, and with improvements in these values at Week 12 by regression analysis. Treatment effects occurred rapidly (within 2 wks) and were maintained through 24 weeks of treatment. CONCLUSION: Adalimumab significantly improved symptoms of pain, fatigue, and stiffness in patients with AS. Improved symptoms were associated with improved physical function and HRQOL.     

Adalimumab response in patients with early versus established rheumatoid arthritis: DE019 randomized controlled trial subanalysis

In recent years, there has been a shift in the therapeutic approach to rheumatoid arthritis (RA), with emphasis on early therapy. The DE019 trial demonstrated adalimumab efficacy in patients with RA. This subanalysis compares response to adalimumab based on clinical, functional, and radiographic outcomes in patients with early versus established RA. Patients enrolled in the DE019 trial were divided into two groups based on disease duration (≤3 years = early RA; >3 years = established RA). Data from 407 patients with RA were included, with 78 early (41 adalimumab, 37 placebo) and 329 established (166 adalimumab, 163 placebo) patients. Patients with early disease achieved slightly greater American College of Rheumatology 20 (20% or more improvement or ACR20), 50, and 70 responses of 61%, 46.3%, and 24.4%, respectively, at 52 weeks, compared with those with established disease, with ACR20, 50, and 70 responses of 56%, 37.3%, and 19.9%, respectively. The Health Assessment Questionnaire score improvement between adalimumab and placebo in patients with early disease (0.44) was greater than that for those with established disease (0.25). With adalimumab treatment, there was a statistically significant mean reduction in total Sharp score progression relative to placebo (5.32) in early disease compared with established disease (2.06). While adalimumab is effective for RA of all disease durations, there is a trend toward superior clinical, functional, and radiographic outcomes in patients with early disease.     

Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients

OBJECTIVE: Fatigue has been recognized as an important domain in rheumatoid arthritis (RA) clinical trials and in patient care and outcome. However, lengthy fatigue questionnaires cannot be easily used in clinical care, and there are no data for the comparative performance of various short and long questionnaires. We compared a single-item visual analog scale (VAS) with 3 longer fatigue questionnaires, investigating 4 fatigues scales: the Multi-dimensional Assessment of Fatigue (MAF), the vitality scale from the Medical Outcomes Study Short Form 36 (SF-36), the Brief Fatigue Inventory (BFI), and the VAS. METHODS: Participants in a longitudinal outcome study of RA (N = 7760) completed the 4 questionnaires, and a subset of 5155 completed the same fatigue scales 6 months later. RESULTS:All questionnaires were highly correlated and were correlated at similar levels with clinical variables. The 3 longer questionnaires had slightly greater reliability in cross-sectional analyses, but the VAS was as good as or better than the longer questionnaires when sensitivity to change was considered. CONCLUSION: The single item VAS performs as well as or better than longer scales in respect to sensitivity to change, and is at least as well correlated with clinical variables as longer scales. The VAS fatigue scale is suitable for routine use in clinical care, an advantage that is lacking for the other scales. These results do not indicate advantages for longer fatigue scales compared with the VAS.     

Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.     

Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment

OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.     

Health-related quality of life outcomes in patients with active ankylosing spondylitis treated with adalimumab: results from a randomized controlled study

OBJECTIVE: To evaluate the impact of adalimumab on health-related quality of life (HRQOL) in patients with active ankylosing spondylitis (AS). METHODS: Patients >or=18 years enrolled in the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in Ankylosing Spondylitis, a randomized controlled study, were randomly assigned to receive either adalimumab 40 mg subcutaneously or placebo every other week for 24 weeks. ASsessment of Ankylosing Spondylitis (ASAS) International Working Group criteria were used to evaluate clinical efficacy. HRQOL outcomes were assessed using the Short Form 36 (SF-36) Health Survey and Ankylosing Spondylitis Quality of Life (ASQoL) Questionnaire. RESULTS: A total of 315 patients enrolled (208 in the adalimumab group and 107 in the placebo group). Patients in the adalimumab group showed significant improvements in SF-36 Physical Component Summary (PCS) and ASQoL scores versus placebo at weeks 12 and 24 (P < 0.001). The observed differences between adalimumab and placebo patients exceeded the a priori minimum important difference (MID) at the group level, and significantly more adalimumab-treated patients achieved improvements greater than the MID on the patient level. These data suggest the HRQOL improvements were clinically meaningful. No differences were observed in SF-36 Mental Component Summary (MCS) scores. Significant differences favoring adalimumab were observed for SF-36 domains physical function, bodily pain, role-physical, general health, vitality, social function, and role-emotional. There was significant association between HRQOL improvements (measured by SF-36 PCS and MCS, and ASQoL scores) and ASAS clinical responses (P < 0.001). CONCLUSION: Adalimumab significantly improved physical health status and overall HRQOL through 24 weeks in patients with active AS.     

阿达木单抗联合甲氨蝶呤治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究

目的 评价阿达木单抗联合甲氨蝶呤(MTX)治疗类风湿关节炎(RA)的疗效与安全性.方法 随机、双盲、平行、安慰剂对照的多中心临床试验.302例入组前已经至少接受MTX 3个月治疗且剂量稳定≥28 d的活动性RA患者,随机分为40 mg阿达木单抗+MTX组(A组,121例)、80 mg阿达木单抗+MTX组(B组,121例)、安慰剂+MTX组(C组,60例).患者隔周皮下注射阿达木单抗或安慰剂,双盲治疗期为12周.完成双盲期的患者进入后12周开放期,3组患者均予隔周皮下注射40 mg阿达木单抗.在双盲期和开放期的患者同时继续接受研究前稳定剂量的MTX.观察主要疗效指标[双盲期治疗第12周修改的美国风湿病学会疗效标准提高20%(ACR20)有效率]、次要疗效指标[第24周ACR20有效率;第12周、第24周修改的美国风湿病学会疗效标准提高50%(ACR50)、修改的美国风湿病学会疗效标准提高70%(ACR70)有效率]、压痛关节数、肿胀关节数、疼痛视觉模拟评分,医生对疾病活动性整体评价、患者对疾病活动性整体评价、健康评价问卷(HAQ)评分、评估健康相关生活质量简表36(SF-36)评分及不良事件.结果 (1)双盲期,ACR20有效率C组为35.0%,A组为57.0%,B组为51.2%,A组、B组与C组比较,P<0.05;A组ACR50、ACR70有效率分别为32.2%、15.7%,与C组比较,P<0.05;A组压痛关节数、肿胀关节数、C反应蛋白水平的改善优于C组(P<0.05);B组肿胀关节数、C反应蛋白水平的改善优于C组(P<0.05).(2)开放期,A组、B组ACR20、ACR50、ACR70有效率仍维持或有所提高,而C组的ACR20、ACR50、ACR70有效率则升高至与A组、B组类似的水平.在压痛关节数、肿胀关节数、疼痛视觉模拟评分、HAQ、SF-36方面,3组均比基线、第12周时有更明显的好转.(3)双盲期与开放期中超过5%的患者有不良事件(上呼吸道感染、鼻咽炎和注射部位瘙痒),多数为轻～中度.有3例患者在研究期间出现结核病.在双盲期,有3例(1.2%)受试者出现了严重不良事件,但研究者判定与药物无关或可能无关.在开放期,有8例(2.7%)受试者出现了严重不良事件,其中3例判定与药物无关或可能无关.结论 阿达木单抗联合MTX治疗RA的疗效优于单用MTX,可显著提高治疗有效率并持续改善症状、体征、实验室炎性活动指标,减少功能障碍并提高整体生活质量,同时具有良好的安全性与耐受性.     

Improvement in patient‐reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti–tumor necrosis factor therapy

Objective

To assess the effects of treatment with rituximab plus methotrexate on patient‐reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti–tumor necrosis factor therapy.

Methods

Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health‐related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent‐to‐treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), and Short Form 36 (SF‐36) was determined.

Results

Rituximab patients had statistically significantly greater pain relief. The FACIT‐F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean ± SD change from baseline for the SF‐36 Physical Component Score was 6.64 ± 8.74 for rituximab patients and 1.48 ± 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF‐36 Mental Component Score was 5.32 ± 12.41 for rituximab patients and 2.25 ± 12.23 for placebo patients (P = 0.0269).

Conclusion

Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient‐reported pain, fatigue, functional disability, health‐related quality of life, and disease activity. These effects were sustained throughout the study.     

A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. RESULTS: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). CONCLUSIONS: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.     

Health-related quality of life in women with symptomatic hand osteoarthritis: a comparison with rheumatoid arthritis patients, healthy controls, and normative data

OBJECTIVE: Data on the burden of disease and impact on health-related quality of life (HRQOL) in hand osteoarthritis (OA) are limited. The goal of this study was to compare HRQOL in patients with hand OA with HRQOL in patients with rheumatoid arthritis (RA), healthy controls, and normative data from the general population. METHODS: A total of 190 women with hand OA were compared with 194 women with RA and 144 healthy women of the same age. Health status was measured using the Short Form 36 (SF-36), Short Form 6D (SF-6D), modified Health Assessment Questionnaire (M-HAQ), pain and fatigue visual analog scales, and grip strength. Scores were compared by analysis of variance and a multivariate analysis of covariance, adjusting for age, number of comorbidities, and years of education. Gaps between patients and population subjects were assessed by calculating S scores on all dimensions of the SF-36. RESULTS: Hand OA and RA patients had worse scores on all assessed dimensions of subjective health compared with healthy controls. RA patients showed poorest general health (SF-36), poorest physical function (M-HAQ, SF-36 physical, grip strength), and highest level of fatigue compared with hand OA patients. Hand OA patients reported poorer mental health. Mean utility scores (SF-6D) in hand OA and RA were 0.64 and 0.63, respectively, with a mean difference compared with healthy controls of 0.13 in hand OA and 0.14 in RA patients. S scores confirmed a marked disparity between individuals with a rheumatic diagnosis (hand OA, RA) and population subjects. CONCLUSION: This study illustrates that patients with hand OA experience a broad impact on HRQOL compared with healthy controls. Fatigue and physical function are worse in RA than hand OA.