Validation of new potential targets for remission and low disease activity in psoriatic arthritis in patients treated with golimumab.

OBJECTIVES: Treat to target recommendations for PsA state that the target of treatment should be remission or, at the very least, low disease activity. Different clinical indexes have been proposed to define these disease states including the minimal disease activity criteria and the Disease Activity Index for PsA (DAPSA) scores, which have 7 and 4-5 domains, respectively. Using a Canadian cohort, the objectives were to calculate the proportion of patients achieving these criteria, their prognostic value and the overall patient impact of these disease states. METHODS: BioTRAC is an ongoing, prospective registry of inflammatory arthritis patients. 188 PsA patients treated with golimumab were included. Data collected at baseline, 6 and 12 months were used. RESULTS: Between 15.6% and 38.3% of patients achieved remission, and 37.4-77.7% achieved low disease activity at 6 and 12 months' follow-up. Patients achieving any minimal disease activity target and DAPSA low disease activity had significantly lower swollen joint count, tender joint count, psoriasis area and severity index, dactylitis and enthesitis scores compared with non-achievers (P < 0.05). Higher HAQ scores (P < 0.03) were observed in patients achieving remission with remaining dactylitis or active skin disease. CONCLUSION: Very low disease activity was the most stringent new potential target for remission in PsA. There was a high level of agreement between scores, although residual activity in dactylitis and skin despite DAPSA remission may affect patient function. Patients achieving either DAPSA endpoint, however, did not show a significant reduction in skin disease, indicating that those two criteria are more restricted to joint symptoms.

Real-World Incidence and Determinants of Infection in Patients With Rheumatoid Arthritis Treated With Golimumab After a Median Follow-Up Time of 27 Months.

OBJECTIVE: To characterize the long-term incidence of infection in patients with rheumatoid arthritis (RA) treated with subcutaneous golimumab (GOL) in Canadian routine care, assess the effect of infections on GOL retention, and explore factors associated with infection incidence. METHODS: Patients with RA enrolled in the Biologic Treatment Registry Across Canada (BioTRAC) initiating GOL treatment were included. The incidence density rates (IDRs) of total infection (TI), serious infection (SI), and nonserious infection (NSI) were calculated for the overall follow-up (90 months) and by 6-month intervals. Determinants of infection over time or within the first 6 months were explored using generalized estimating equation models and logistic regression, respectively. RESULTS: Five hundred thirty patients were included; mean baseline age was 57.7 years and RA duration was 8.0 years. Over an average follow-up of 27.0 months, the IDR for TIs was 35.1 events per 100 person-years (PYs), the majority occurring during the first 6 months; IDRs for NSIs and SIs were 32.9 and 2.2 events per 100 PYs, respectively. No predictors were identified for infection incidence within 6 months. Comorbid pulmonary disease was associated with significantly higher odds of TIs and NSIs over time, whereas higher age and high corticosteroid (CS) dose (> 5 mg/day) predicted higher odds of SIs. Incidence of SIs, but not NSIs, was associated with significantly higher odds of GOL discontinuation. CONCLUSION: Long-term GOL treatment was associated with relatively low infection rates, most being nonserious and occurring during the first 6 months. Pulmonary disease, higher age, and high CS dose were identified as significant predictors of infections. SIs, but not NSIs, predicted higher odds of GOL discontinuation. (ClinicalTrials.gov: NCT00741793).

Sustained low functional impairment in axial spondyloarthritis (axSpA): which are the primary outcomes that should be targeted to achieve this?

OBJECTIVES: To (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort. METHODS: Biologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models. RESULTS: Eight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months. CONCLUSION: Sustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.

Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies.

OBJECTIVE: To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. METHODS: The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. RESULTS: Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). CONCLUSIONS: Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.

Usage and Adherence of Seven Advanced Therapies with Differing Mechanisms of Action for Inflammatory Arthritis in Canada.

INTRODUCTION: This retrospective, observational study aimed to analyze and assess adherence, persistence, dosing, and use of concomitant medications of seven self-administered target drugs (abatacept, golimumab, secukinumab, tocilizumab, ustekinumab, apremilast, and tofacitinib) that are currently available in Canada for the treatment of inflammatory arthritis (IA). METHODS: We used IQVIA's longitudinal claims databases, which include private drug plans and public plans. Patients with IA identified using a proprietary indication algorithm who initiated treatment with any of the target drugs between January 2015 and February 2019 were selected and followed for 12 months. RESULTS: Golimumab and apremilast had the highest proportion of patients (~ 75%) who were bio-naïve and secukinumab had the fewest bio-naïve patients (~ 43%). The oral therapies, apremilast and tofacitinib, had the lowest percentage of adherent patients (73% and 71%) followed by abatacept (83%), while the remaining drugs had adherence around 90%. Secukinumab and tofacitinib had the highest 12-month persistence rate (63% and 61%), while abatacept and apremilast had the lowest persistence rate (52% and 47%). Oral corticosteroid (OCS) use was not significantly associated with adherence. Tocilizumab, secukinumab, and ustekinumab had the highest proportion of patients (> 20%) with dose escalation at 3-4 months from index. OCS and conventional disease-modifying antirheumatic drugs (cDMARD) use decreased in post-index period across all target drugs. CONCLUSION: This study identified substantial differences in patient baseline characteristics. Patients on injectable biologics were more likely to be adherent compared with those on oral drugs, possibly owing to longer dosing intervals. Other outcomes at 12 months appeared similar as evidenced by tapering of concomitant medications, although differences in persistence and dose escalation were noted.

Long-term effectiveness and safety of infliximab, golimumab and ustekinumab in patients with psoriatic arthritis from a Canadian prospective observational registry.

OBJECTIVES: The objectives of this study were to describe the demographic profile and baseline disease characteristics of patients with psoriatic arthritis (PsA) treated with either infliximab (IFX), subcutaneous golimumab (GLM) or ustekinumab (UST) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety. METHODS: Patients with PsA were enrolled into the Biologic Treatment Registry Across Canada registry (ClinicalTrials.gov Identifier: NCT00741793) from 2005 to 2017. The study visits occurred at study enrolment (baseline) and every 6 months thereafter. Effectiveness was assessed by changes in disease parameters (joint counts, Psoriasis Area Severity Index (PASI), Health Assessment Questionnaire, patient/physician global, minimal disease activity, enthesitis, dactylitis, erythrocyte sedimentation rate, C reactive protein). Improvements from baseline were explored with the paired t-test and the McNemar's test. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates. RESULTS: A total of 111 IFX-treated, 281 GLM-treated and 70 UST-treated patients were enrolled. Most baseline disease parameters remained similar over time in all three cohorts. UST-treated patients had lower mean baseline Disease Activity Score in 28 joints CRP, swollen joint based on 28 joints and higher PASI compared with patients treated with GLM. Treatment with IFX, GLM and UST was associated with significant improvements in all disease parameters over time (p<0.001) from baseline up to 84, 84 and 40 months, respectively.AEs were reported for 74.8%, 69.8% and 52.9% (138, 114 and 115 events/100 patient-years (PYs)) covering 325, 567 and 87 years of exposure for IFX-treated, GLM-treated and UST-treated patients, respectively. Severe AEs were reported in 19.8%, 8.5% and 5.7% (8.8, 7.2 and 8.0 events/100 PYs) in IFX-treated, GLM-treated and UST-treated patients, respectively. The proportion of patients who discontinued treatment were 63.1%, 50.9% and 50.0%, respectively. CONCLUSIONS: IFX, GLM and UST treatment significantly reduced disease activity and improved functionality in patients with PsA followed by routine clinical practice and had a safety profile similar to that previously reported in the literature. TRIAL REGISTRATION NUMBER: NCT00741793.

Long-term effectiveness and safety of infliximab and golimumab in ankylosing spondylitis patients from a Canadian prospective observational registry.

BACKGROUND: The objectives of this study were to describe the profile of ankylosing spondylitis (AS) patients treated with either infliximab (IFX) or subcutaneous golimumab (GLM) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety. METHODS: AS patients who were eligible for treatment with IFX or subcutaneous GLM as per their respective Canadian product monographs were enrolled into the BioTRAC registry from 2005 to 2017. The study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in clinical outcomes and acute phase reactants. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates. RESULTS: A total of 389 IFX- and 421 GLM-treated patients were enrolled. A significant decrease in disease duration at baseline was observed in the IFX cohort, from a median of 8.0 in 2005-2008 to 1.0 years in 2009-2015 (p < 0.001). A reduction in baseline BASFI score (p = 0.011) and proportion of patients in ASDAS very high disease activity (p = 0.004) was also observed over time. Meanwhile, in the GLM cohort, most disease parameters remained similar from 2010 to 2017. Treatment with both agents significantly improved all disease parameters over time with similar efficacy between the two agents. The incidence of AEs and SAEs were 136 and 131 events/100 PYs and 10.5 and 8.45 events/100 PYs for IFX- and GLM-treated patients, respectively. CONCLUSION: Both IFX and GLM treatment in AS significantly reduced disease activity in most outcome measures in a similar fashion and were well tolerated in Canadian routine care. TRIAL REGISTRATION: NCT00741793 .

Long-term effectiveness and safety of infliximab, golimumab and golimumab-IV in rheumatoid arthritis patients from a Canadian prospective observational registry.

BACKGROUND: Long-term clinical registries are essential tools to evaluate new therapies in a patient population that differs from those in randomized clinical trials. The objectives are to describe the profile of rheumatoid arthritis (RA) patients treated with anti-TNF agents in Canadian routine care. METHODS: RA patients eligible for treatment with Infliximab (IFX), golimumab (GLM) or intravenous golimumab (GLM-IV) as per their respective Canadian product monographs were enrolled into the BioTRAC registry between 2002 and 2017. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in disease activity. Safety was evaluated by the incidence of adverse events (AEs) and drug survival. RESULTS: Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females ranged from 77.0-86.6%, the mean ages from 55.8-57.7 and the mean disease duration from 6.5-8.6 years. A significant decrease in baseline disease duration and disease activity parameters (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) was observed over time. Treatment with IFX, GLM- and GLM-IV significantly improved all disease parameters over time. The incidence of AEs was 105, 113 and 82.6 /100 PYs and the incidence of SAEs was 11.7, 11.2 and 4.68 /100 PYs for IFX, GLM- and GLM-IV-treated patients, respectively. CONCLUSION: Differences in baseline characteristics between patients treated with an anti-TNFs over time shows the evolution of treatment modalities over time. All treatments significantly reduced disease activity and improved functionality in a similar fashion. The incidence of adverse events was consistent with the safety profiles of IFX and GLM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00741793 (Retrospectively registered on August 26, 2008).

Determination of the minimal clinically important difference for seven fatigue measures in rheumatoid arthritis.

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of seven measures of fatigue in rheumatoid arthritis. STUDY DESIGN AND SETTING: A cross-sectional study design based on interindividual comparisons was used. Six to eight subjects participated in a single meeting and completed seven fatigue questionnaires (nine sessions were organized and 61 subjects participated). After completion of the questionnaires, the subjects had five one-on-one 10-minute conversations with different people in the group to discuss their fatigue. After each conversation, each patient compared their fatigue to their conversational partners on a global rating. Ratings were compared to the scores of the fatigue measures to estimate the MCID. Both nonparametric and linear regression analyses were used. RESULTS: Nonparametric estimates for the MCID relative to "little more fatigue" tended to be smaller than those for "little less fatigue." The global MCIDs estimated by linear regression were: Fatigue Severity Scale, 20.2; Vitality scale of the MOS-SF36, 14.8; Multidimensional Assessment of Fatigue, 18.7; Multidimensional Fatigue Inventory, 16.6; Functional Assessment of Chronic Illness Therapy-Fatigue, 15.9; Chalder Fatigue Scale, 9.9; 10-point numerical Rating Scale, 19.7, for normalized scores (0-100). The standardized MCIDs for the seven measures were roughly similar (0.67-0.76). CONCLUSION: These estimates of MCID will help to interpret changes observed in a fatigue score and will be critical in estimating sample size requirements.

Real-world validation of the minimal disease activity index in psoriatic arthritis: an analysis from a prospective, observational, biological treatment registry.

OBJECTIVE: To describe the minimal disease activity (MDA) rate over time in patients with psoriatic arthritis (PsA) receiving antitumour necrosis factor agents, evaluate prognostic factors of MDA achievement and identify the most common unmet criteria among MDA achievers. DESIGN: Biologic Treatment Registry Across Canada (BioTRAC): ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis or PsA with infliximab (IFX), golimumab (GLM) or ustekinumab. SETTING: 46 primary-care Canadian rheumatology practices. PARTICIPANTS: 223 patients with PsA receiving IFX (enrolled since 2005) and GLM (enrolled since 2010) with available MDA information at baseline, 6 months and/or 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: MDA was defined as ≥5 of the following criteria: 28-item tender joint count (TJC28) ≤1, 28-item swollen joint count (SJC28) ≤1, Psoriasis Area and Severity Index (PASI) ≤1 or body surface area≤3, Pain Visual Analogue Scale (VAS) ≤15 mm, patient's global assessment (PtGA) (VAS) ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, tender entheseal points ≤1. Independent prognostic factors of MDA achievement were assessed with multivariate logistic regression. RESULTS: MDA was achieved by 11.7% of patients at baseline, 43.5% at 6 months, 44.8% at 12 months and 48.8% at either 6 or 12 months. Among MDA achievers at 6 months, 75.7% had sustained MDA at 12 months. Lower baseline HAQ (OR=0.210; 95% CI: 0.099 to 0.447) and lower TJC28 (OR=0.880; 95% CI: 0.804 to 0.964), were significant prognostic factors of MDA achievement over 12 months of treatment. The most commonly unmet MDA criteria among MDA achievers was patient reported pain (25%), PtGA (15%) and PASI (12%). CONCLUSIONS: Almost 50% of patients treated with IFX or GLM in routine clinical care achieved MDA within the first year of treatment. Lower baseline HAQ and lower TJC28, were identified as significant prognostic factors of MDA achievement. The most commonly unmet criteria in patients who achieved MDA were pain, PtGA and PASI. TRIAL REGISTRATION NUMBER: BioTRAC (NCT00741793).

Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis.

OBJECTIVES: To describe the profile of patients with ankylosing spondylitis (AS) treated with infliximab in Canadian routine care and to assess the effectiveness and safety of infliximab in real world. SETTING: 46 primary care rheumatology practices across Canada. PARTICIPANTS: 303 biological-naïve patients with AS or patients previously treated with a biological for <6 months and who were eligible for infliximab treatment as per routine care within the Biologic Treatment Registry Across Canada (BioTRAC). INTERVENTION: Not applicable (non-interventional study). PRIMARY AND SECONDARY OUTCOMES: Effectiveness was assessed with changes in disease parameters (AS Disease Activity Score (ASDAS), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Health Assessment Questionnaire Disease Index (HAQ-DI), physician global assessment of disease activity (MDGA), patient global disease activity (PtGA), back pain, C-reactive protein, erythrocyte sedimentation rate (ESR), morning stiffness). Safety was assessed with the incidence of adverse events (AEs). RESULTS: Of the 303 patients included, 44.6% were enrolled in 2005-2007 and 55.4% in 2008-2013. Patients enrolled in 2005-2007 had significantly higher MDGA and ESR at baseline while all other disease parameters examined were numerically higher with the exception of PtGA. Treatment with infliximab significantly (p<0.001) improved all disease parameters over time in both groups. At 6 months, 56% and 31% of patients achieved clinically important (change≥1.1) and major (change≥2.0) improvement in ASDAS, respectively; at 48 months, these proportions increased to 75% and 50%, respectively. Among patients unemployed due to disability at baseline, 12.1% returned to work (mean Kaplan-Meier (KM)-based time=38.8 months). The estimated retention rate at 12 and 24 months was 78.3% and 60.1%, respectively. The profile and incidence of AEs were comparable to data previously reported for tumour necrosis factor-α inhibitors. CONCLUSIONS: Characteristics of patients with AS at infliximab initiation changed over time towards lower disease activity and shorter disease duration. Infliximab treatment significantly reduced disease activity independent of treatment initiation year, although patients enrolled in recent years achieved lower disease activity over 48 months. TRIAL REGISTRATION NUMBER: NCT00741793.

Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population.

OBJECTIVE: To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. METHODS: Biological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. RESULTS: 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). CONCLUSIONS: Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered. TRIAL REGISTRATION NUMBER: NCT00741793.

Depressive symptoms and rheumatoid arthritis: spouse empathic responding as a buffer.

OBJECTIVE: To examine the effects of depressive symptoms and spouse empathic responding on patient disability and marital quality over time and to identify factors that contribute to patients perceiving their spouses as responding empathically to their rheumatoid arthritis (RA). METHODS: Patients diagnosed with RA and their spouses (n = 133 couples) independently completed mailed questionnaires at baseline and 1 year later. Patients completed measures of functional impairment, marital quality, depressive symptoms, and perceived empathic responding from their spouse. Spouses reported their own depressive symptoms and empathic responding behavior. RESULTS: Perceived empathic responding was found to interact with spouse depressive symptoms, contributing significantly to the prediction of patient functional impairment at followup. Only when spouse empathic responding was low was spouse depression associated with greater patient functional impairment 1 year later. Similarly, in the model predicting patient marital quality at followup, there were significant 2-way interactions between perceived empathic responding and both spouse depressive symptoms and patient depressive symptoms. Only when spouse empathic responding was low did patient or spouse depression significantly predict poorer marital quality at followup. Patient perceptions of spouse empathic responding were found to depend on spouse reports of their own empathic responding, patient marital satisfaction, and the interaction of patient depressive symptoms and marital satisfaction. CONCLUSION: Empathic responding from the spouse was found to buffer against the negative effects of spouse depression on functional and marital outcomes for patients with RA. In developing couple-oriented RA treatments, increasing perceived empathic responding could serve as a useful target for intervention.

Effectiveness and safety of infliximab in rheumatoid arthritis: analysis from a Canadian multicenter prospective observational registry.

OBJECTIVE: To describe the profile of rheumatoid arthritis (RA) patients treated with infliximab in Canadian routine care and to assess the real-world effectiveness and safety of infliximab. METHODS: Biologics-naive RA patients from the Biologic Treatment Registry Across Canada were stratified based on their enrollment year. Effectiveness was assessed with the changes in clinical/laboratory parameters and patient-reported outcomes and the achievement of minimal disease activity and remission. Safety was assessed with the incidence of treatment-emergent adverse events (AEs). RESULTS: Among 628 patients, 45.9%, 34.6%, and 19.6% were enrolled between 2002-2005, 2005-2008, and 2008-2011, respectively. Patients recruited in more recent years had significantly lower Disease Activity Score with a 28-joint count using the C-reactive protein level (DAS28-CRP), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), swollen joint count in 28 joints, tender joint count in 28 joints, physician's global assessment of disease activity, patient's global assessment of disease activity, Health Assessment Questionnaire disability index, pain, erythrocyte sedimentation rate, and CRP level (P < 0.01 for all). Patient management also changed with a trend to initiate infliximab after failure of fewer disease-modifying antirheumatic drugs (DMARDs). Six-month treatment with infliximab resulted in statistically significant and clinically important improvements in all disease parameters examined, which were sustained over 36 months. The cumulative probability of achieving remission by 36 months, as defined by the DAS28, SDAI, and CDAI, was 56.2 (95% confidence interval [95% CI] 47.8-64.8), 31.0 (95% CI 23.8-39.8), and 36.2 (95% CI 28.5-45.3), respectively, which was significantly greater in patients with lower baseline disease activity. The profile and incidence of AEs were comparable to data previously reported for tumor necrosis factor α inhibitors. CONCLUSION: RA patient characteristics at infliximab initiation changed over time toward lower disease activity. Furthermore, a trend to treat patients with fewer DMARDs before initiation of infliximab was observed. However, treatment with infliximab was effective in significantly reducing disease activity independent of the treatment initiation year.

Do spouses know how much fatigue, pain, and physical limitation their partners with rheumatoid arthritis experience? Implications for social support.

OBJECTIVE: To determine whether perceptions of clinical manifestations (fatigue, pain, and physical limitation) of rheumatoid arthritis (RA) differ between spouses and their partners with RA, and to determine whether the differences are associated with the perception of beneficial and problematic spousal social support. METHODS: English-speaking adults with RA of ≥ 6 months' duration and their spouses (n = 222 couples) completed standardized questionnaires for fatigue, pain, physical limitation, beneficial spousal support, and problematic spousal support. Spouses completed questionnaires based on their perception of their partner with RA. Agreement scores for fatigue, pain, and physical limitation were calculated by subtracting spouse scores from the scores of the partner with RA. Agreement levels were defined a priori: agreement (within ± one-half of a minimum clinically important difference [MCID] unit), overestimator (< one-half an MCID), and underestimator (> one-half an MCID). Separate hierarchical linear regression models were used to measure the association between beneficial support and problematic support after adjusting for RA duration, physical health, sex, educational level, relationship duration, and satisfaction. RESULTS: Response rate for couples was 82%. Relative to participants with RA, spouses overestimated fatigue (26%), pain (29%), and physical limitation (39%), and underestimated fatigue (11%), pain (17%), and physical limitation (34%). After statistically controlling for demographic, disease, and psychosocial variables, participants with RA whose spouses underestimated fatigue received more problematic support (R(2) = 3.7%, P = 0.002), as did those whose spouses underestimated or overestimated physical limitation (R(2) = 3.4%, P = 0.017). CONCLUSION: Persons with RA perceived more problematic spousal support when their spouse underestimated fatigue, or underestimated or overestimated physical limitation levels.

Spouse depression and disease course among persons with rheumatoid arthritis.

OBJECTIVE: To examine the role of spouse mood in the disability and disease course of persons with rheumatoid arthritis (PWRA). METHODS: A total of 133 married PWRA completed questionnaires, including the Rheumatoid Arthritis Disease Activity Index and the Disabilities of the Arm, Shoulder, and Hand, assessing PWRA arthritis disease activity and disability, respectively, at 2 time points 1 year apart. In addition, both PWRA and their spouses completed the Center for Epidemiologic Studies Depression Scale, a standardized community measure of depression at both time points. RESULTS: Multiple regression analysis revealed spouse depressive symptoms at initial assessment to be predictive of followup PWRA disability and disease activity, even after controlling for initial levels of PWRA depression, disability, disease activity, age, number of years married, education, disease duration, and employment. Specifically, higher levels of spouse depression predicted worse disease course over a 1-year period for PWRA, as indicated by higher reports of subsequent PWRA disability and disease activity. CONCLUSION: Our findings highlight the key role played by the spouse in PWRA disease course, and point to the importance of including the spouse in clinical interventions. Implications for theory, research, and treatment are discussed with a focus on examining pathways through which spouse depressive symptoms may affect PWRA disease course and disability.

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.

People with arthritis and their families in rehabilitation, care and research.

PURPOSE OF REVIEW: People with arthritis play major roles in treatment and research. This review summarises the current knowledge on tools for enhancing shared-decision making in arthritis care; individual and family involvement in rehabilitation; and the consumer's role in arthritis research. RECENT FINDINGS: There are discrepancies in the use of appropriate arthritis treatment. To facilitate evidence-informed treatment choices, a number of decision aids have been developed. A recent systematic review concluded that decision aids could improve the shared-decision making process in a variety of diseases; but only one clinical trial was found on a musculoskeletal condition (back surgery). The evidence on family member participation in arthritis education programs is mixed, partly due to a lack of content specifically targeting family members in some studies. Finally, people with arthritis are playing important roles as collaborators in research. Early experience indicates a mutually beneficial relationship for both the individual and researchers. SUMMARY: This review offers three recommendations: First, further clinical trials are needed to test the effectiveness of decision aids in arthritis management. Second, education programs involving strong social support training for family members may improve client outcomes. Third, we encourage further studies to examine the experiences and challenges of people living with arthritis when participating as research partners.

A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.

OBJECTIVE: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS: Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION: In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.

A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis.

OBJECTIVE: To assess the efficacy of topical Tripterygium wilfordii (TW), a Chinese herbal therapy, in rheumatoid arthritis (RA). METHODS: A 6 week randomized double blind placebo controlled study of 61 patients with RA meeting American College of Rheumatology (ACR) criteria was conducted in China. The primary outcome was a modified ACR-20 response rate, analyzed by logistic regression analysis. RESULTS: The modified ACR-20 response rate differed significantly (topical TW 58% vs placebo 20%; p = 0.002). There was an 8.1-fold (95% CI 1.9-35.4) increase in the modified ACR-20 response for the TW compared to the placebo group, adjusted for age and erythrocyte sedimentation rate. CONCLUSION: Topical TW appears efficacious for the treatment of RA, but larger studies are needed.