Could accelerated aging explain the excess mortality in patients with seropositive rheumatoid arthritis?

Objective

To determine whether the mortality pattern in patients with seropositive rheumatoid arthritis (RA) is consistent with the concept of accelerated aging, by comparing the observed mortality rates in patients with RA with the age‐accelerated mortality rates from the general population.

Methods

A population‐based inception cohort of patients with seropositive RA (according to the American College of Rheumatology 1987 criteria) was assembled and followed up for vital status until July 1, 2008. The expected mortality rate was obtained by applying the death rates from the general population to the age, sex, and calendar year distribution of the RA population. The observed mortality was estimated using Kaplan‐Meier methods. Acceleration factors for the expected mortality were estimated in accelerated failure time models.

Results

A total of 755 patients with seropositive RA (mean age 55.6 years, 69% women) were followed up for a mean of 12.5 years, during which 315 patients died. The expected median survival was age 82.4 years, whereas the median survival of the RA patients was age 76.7 years. Results of statistical modeling suggested that, in terms of mortality rates, patients with RA were effectively 2 years older than actual age at RA incidence, and thereafter the patients underwent 11.4 effective years of aging for each 10 years of calendar time.

Conclusion

The overall observed mortality experience of patients with seropositive RA is consistent with the hypothesis of accelerated aging. The causes of accelerated aging in RA deserve further investigation.

     

Long‐term mortality and renal outcome in a cohort of 100 patients with Lupus Nephritis

Objective

To evaluate the long‐term mortality and renal outcome in a cohort of Danish patients with lupus nephritis (LN) and to identify outcome predictors among findings registered at the time of the first renal biopsy.

Methods

The cohort consisted of 100 patients diagnosed with LN (World Health Organization classes I–VI) between 1971 and 1995 and followed for a median duration of 14.7 years (range 0.01–36.9 years). Standardized mortality ratios (SMRs) were calculated on the basis of national age‐, sex‐, and calendar‐year period–specific death rates.

Results

Thirty‐seven deaths occurred in the cohort, corresponding to an overall SMR of 6.8 (95% confidence interval [95% CI] 4.9–9.4). Excess mortality was observed throughout followup. The SMR estimates were 9.0 (95% CI 4.7–17.1), 6.2 (95% CI 4.0–9.5), and 6.6 (95% CI 3.1–13.8) for patients diagnosed during the calendar‐year periods 1971–1979, 1980–1989, and 1990–1995, respectively. The cumulative renal survival after 5, 10, and 20 years of followup was 87%, 83%, and 73%, respectively. The risk of end‐stage renal disease (ESRD) did not decrease significantly across calendar‐year periods. Systolic blood pressure ≥180 mm Hg, focal segmental nephritis, and advanced sclerosing nephritis were identified as baseline predictors of death in multivariate regression analyses, while systolic blood pressure ≥180 mm Hg, serum creatinine level ≥140 μmoles/liter, and diagnostic delay predicted progression to ESRD.

Conclusion

LN is associated with excess long‐term mortality, and patients may progress to ESRD even after prolonged followup. Our analyses indicate that focal segmental histopathology at disease onset constitutes an important risk factor for death among LN patients. Moreover, our data underscore the importance of early intervention, blood pressure control, and long‐term followup in LN.     

Survival in rheumatoid arthritis: A population‐based analysis of trends over 40 years

Objective

To evaluate trends in and risk factors for mortality among patients with rheumatoid arthritis (RA) over a 40‐year period.

Methods

A population‐based inception cohort was assembled from among all Rochester, Minnesota residents ages ≥18 years who were first diagnosed with RA (fulfilling the 1987 American College of Rheumatology criteria for RA) between January 1, 1955 and December 31, 1994. Patients were followed up longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Survival was described using the Kaplan‐Meier method. Observed and expected survival were compared using the log‐rank test, and standardized mortality ratios (SMRs) with expected survival were based on the sex and age of the study population and death rates from the Minnesota life tables. Cox proportional hazards models were used to estimate the influence of extraarticular manifestations and comorbidities, controlling for age, sex, body mass index (BMI), smoking, and rheumatoid factor positivity.

Results

Survival in this RA cohort was significantly lower than that expected in the population (P < 0.001) over the entire time period. Patients with RA were at significantly higher risk of death, with an SMR of 1.27 (95% confidence interval 1.13–1.41). Excess mortality among women was more pronounced than among men, with SMRs of 1.41 and 1.08, respectively. Presence of ≥1 extraarticular manifestation was the strongest predictor of mortality after adjusting for age, sex, BMI, smoking, and rheumatoid factor positivity.

Conclusion

Survival in RA patients is significantly lower than expected. The strongest predictors of survival appear to be those related to RA disease complications, specifically, extraarticular manifestations of the disease and comorbidities. More attention should be paid to mortality as an outcome measure in RA.

     

Is the disease course of rheumatoid arthritis becoming milder?: Time trends since 1985 in an inception cohort of early rheumatoid arthritis

Objective

Based on comparisons of short‐term cohort studies or cross‐sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.

Methods

We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985–1990, 1990–1995, 1995–2000, 2000–2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.

Results

The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease‐modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.

Conclusion

The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.

     

Predictors of change in bodily pain in early rheumatoid arthritis: An inception cohort study

Objective

To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA).

Methods

The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1‐year pain data. The ERAN is a hospital‐based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient‐reported components (joint tenderness and visual analog scale score; DAS28‐P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (OR_adj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates.

Results

Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28‐P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (OR_adj 3.41, 95% confidence interval [95% CI] 1.35–8.64) and a high DAS28‐P index at baseline (OR_adj for tertiles 2.09, 95% CI 1.24–3.55). Other conventional RA risk factors did not predict pain changes.

Conclusion

The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28‐P index. A high DAS28‐P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain.     

Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years

OBJECTIVE: To evaluate trends in and risk factors for mortality among patients with rheumatoid arthritis (RA) over a 40-year period. METHODS: A population-based inception cohort was assembled from among all Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (fulfilling the 1987 American College of Rheumatology criteria for RA) between January 1, 1955 and December 31, 1994. Patients were followed up longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Survival was described using the Kaplan-Meier method. Observed and expected survival were compared using the log-rank test, and standardized mortality ratios (SMRs) with expected survival were based on the sex and age of the study population and death rates from the Minnesota life tables. Cox proportional hazards models were used to estimate the influence of extraarticular manifestations and comorbidities, controlling for age, sex, body mass index (BMI), smoking, and rheumatoid factor positivity. RESULTS: Survival in this RA cohort was significantly lower than that expected in the population (P < 0.001) over the entire time period. Patients with RA were at significantly higher risk of death, with an SMR of 1.27 (95% confidence interval 1.13-1.41). Excess mortality among women was more pronounced than among men, with SMRs of 1.41 and 1.08, respectively. Presence of > or =1 extraarticular manifestation was the strongest predictor of mortality after adjusting for age, sex, BMI, smoking, and rheumatoid factor positivity. CONCLUSION: Survival in RA patients is significantly lower than expected. The strongest predictors of survival appear to be those related to RA disease complications, specifically, extraarticular manifestations of the disease and comorbidities. More attention should be paid to mortality as an outcome measure in RA.     

Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis

Objective

To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort.

Methods

We conducted a cross‐sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy–adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C‐reactive protein (CRP) level. We also estimated the difference in DAS28‐CRP associated with increasing fish consumption by 1 serving per week.

Results

Among 176 participants, the median DAS28‐CRP score was 3.5 (interquartile range 2.9–4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28‐CRP compared with subjects who ate fish never to <1 time/month (difference ?0.49 [95% CI ?0.97, ?0.02]). For each additional serving of fish per week, DAS28‐CRP was significantly reduced by 0.18 (95% CI ?0.35, ?0.004).

Conclusion

Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.

     

Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population‐based study

Objective

Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA‐associated ILD.

Methods

We examined a population‐based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival.

Results

Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non‐RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02–19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98–4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed ∼13% to the excess mortality of RA patients when compared with the general population.

Conclusion

Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.

     

Smoking Behavior Changes in the Early Rheumatoid Arthritis Period and Risk of Mortality During Thirty‐Six Years of Prospective Followup

Objective

To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality.

Methods

We identified an incident RA cohort in the Nurses' Health Study (NHS; 1976–2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within 4 years of the RA/index date. We used Cox regression to obtain hazard ratios (HRs) for mortality, comparing sustained smoking cessation to continued smoking.

Results

Among 121,700 women in the NHS, we identified 938 with incident RA matched to 8,951 non‐RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period, compared to 36.1% of comparators (odds ratio for sustained cessation 1.18 [95% confidence interval (95% CI) 0.88, 1.58]). There were 313 deaths (33.4%) in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58 [95% CI 0.33, 1.01]) and comparison (HR 0.47 [95% CI 0.39, 0.58]) cohorts. Women with RA had higher mortality for >5 post‐RA pack‐years (HR 3.67 [95% CI 2.80, 4.81]) than comparators with >5 post‐index pack‐years (HR 1.88 [95% CI 1.62, 2.17]; P < 0.001 for interaction; reference: ever‐smoker non‐RA women with 0 post‐index pack‐years).

Conclusion

Sustained smoking cessation within 4 years of RA diagnosis reduced mortality risk, with a similar effect observed among non‐RA comparators. Smoking >5 pack‐years after RA diagnosis significantly increased mortality beyond the risk of non‐RA comparators.     

Drug survival of adalimumab in patients with rheumatoid arthritis over 10 years in the real-world settings: high rate remission together with normal function ability

The purpose of the study was to estimate the clinical profile of naïve biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28) ≤ 2.6 + Health Assessment Questionnaire (HAQ) ≤ 0.5), low disease activity (DAS28 ≤ 3.2), remission (DAS28 ≤ 2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3 years was 40.6 %, while the global rate of nonswitching patients was 54.7 %. Compared to 2003–2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p < 0.0001) and a significantly higher rate of switching to alternative biologics (log rank, p < 0.0001). No difference in adverse events or effectiveness rate among the calendar periods was found. A substantial proportion of patients (up to 27 %) achieved GCDC at 2 years, regardless of the calendar period. In real-life setting, RA patients starting adalimumab in more recent years had a higher rate of drug discontinuation not related to ineffectiveness or side effects but to switching, probably due to a wider availability of biologics. A meaningful proportion of patients attained GCDC without any difference across calendar periods.     

No increased mortality in patients with rheumatoid arthritis treated with biologics: results from the biologics register of six rheumatology institutes in Japan

Objective

To investigate the influence of biologics on mortality and risk factors for death in rheumatoid arthritis (RA) patients.

Methods

RA patients treated with at least one dose of biologics in daily practice in six large rheumatology institutes (“biologics cohort”) were observed until 15 May 2010 or death, whichever occurred first. Mortality of the biologics cohort and the “comparator cohort” (comprising patients among the IORRA cohort who had never been treated with biologics) was compared to that of the Japanese general population. Factors associated with mortality were assessed by a Cox model.

Results

Among 2683 patients with 6913.0 patient-years of observation, 38 deaths were identified in the biologics cohort. The probability of death in patients lost to follow-up, calculated using the weighted standardized mortality ratio (SMR), was 1.08 [95 % confidence interval (CI) 0.77–1.47] in the biologics cohort and 1.28 (95 % CI 1.17–1.41) in the comparator cohort. Pulmonary involvement was the main cause of death (47.4 %), and the disease-specific SMR of pneumonia was 4.19 (95 % CI 1.81–8.25). Risk factors for death included male gender [hazard ratio (HR) 2.78 (95 % CI 1.24–6.22)], advanced age (HR 1.07, 95 % CI 1.03–1.11), and corticosteroid dose (HR 1.08, 95 % CI 1.01–1.17).

Conclusion

Mortality in RA patients exposed to biologics did not exceed that in patients not exposed to biologics, but death from pulmonary manifestations was proportionally increased in RA patients exposed to biologics.     

Thresholds in disease activity for switching biologics in rheumatoid arthritis patients: experience from a large U.S. cohort

Objective

To examine the threshold in disease activity associated with switching biologic treatment regimens in rheumatoid arthritis (RA) patients in real‐world clinical practice.

Methods

Using data from a prospective observational North American cohort of RA patients through December 30, 2009, patients who initiated a new anti–tumor necrosis factor α (anti‐TNFα) agent with ≥6 months of followup were identified. Patients were classified as switchers or maintainers depending on whether they continued their anti‐TNF treatment or switched (including discontinuation) within 12 months. Level of disease activity measured by the Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints (DAS28) at the time of the switch (corresponding followup visit for maintainers) was examined and random‐effect multivariable logistic regression was used to adjust for covariates.

Results

Mean age and RA duration among 1,549 eligible patients were 56.1 and 9.6 years, respectively, 80% were women, 62% were initiating their first biologic, and 30% were initiating their second biologic. At the time of the switch, the median DAS28 and CDAI score were 3.1 and 8.4 among maintainers and 4.0 and 15.2 among switchers, respectively. Maintainers also experienced a greater amount of reduction in disease activity compared with switchers (CDAI: ?7.7 versus ?2.3, DAS28: ?1.1 versus ?0.3). The threshold to switch decreased over calendar time, with the greatest amount of reduction observed among patients with moderate disease activity.

Conclusion

On average, physicians and patients were willing to continue biologic treatment for patients who were at or near low disease activity. The threshold to switch decreased over time, especially among partial responders.

     

Physician ability to assess rheumatoid arthritis disease activity using an electronic medical record–based disease activity calculator

Objective

To assess physicians' concordance with Disease Activity Score in 28 joints (DAS28) categories calculated by an electronic medical record (EMR)–embedded disease activity calculator, as well as attitudes toward this application.

Methods

Fifteen rheumatologists used the EMR‐embedded disease activity calculator to predict a rheumatoid arthritis (RA) DAS28 disease activity category at the time of each clinical encounter.

Results

Physician‐predicted DAS28 disease activity categories ranged from high (>5.1, 15% of cohort, 66 of 429 patient visits) to moderate (>3.2–5.1, 21% of cohort, 90 of 429 patient visits) to low (2.6–3.2, 29% of cohort, 123 of 429 patient visits) to remission (<2.6, 35% of cohort, 150 of 429 patient visits). Overall concordance between calculated DAS28 results and physician‐predicted RA disease activity was 64%. Using either the physician‐predicted or the calculated DAS28 category as the gold standard, accuracy was greatest for patients in remission (75% and 88% accuracy, respectively) and those with high disease activity (68% and 79% accuracy, respectively), and less for patients with moderate (48% and 62% accuracy, respectively) or low disease activity (62% and 31% accuracy, respectively).

Conclusion

Accurate physician prediction of DAS28 remission and high disease activity categories, even without immediate availability of the erythrocyte sedimentation rate or the C‐reactive protein level at the time of the visit, may be used to guide quantitatively driven outpatient RA management. This article was published online on March 30, 2009. An error was subsequently identified in Figure 4. This notice is included in the online and print versions to indicate that both have been corrected.     

Mortality in Patients With Giant Cell Arteritis: A Cohort Study in UK Primary Care

Objective

To examine whether giant cell arteritis (GCA) is associated with increased all‐cause mortality and whether mortality differs according to age, sex, and calendar year of cohort entry.

Methods

Using the UK‐based Clinical Practice Research Datalink, we identified 9,778 newly diagnosed GCA patients from 1990–2014, and up to 10 nonvasculitis patients randomly matched to each case on age, sex, practice, and years of history before cohort entry. We used Cox regression to estimate adjusted hazard ratios (HRs) for mortality of GCA patients in comparison to nonvasculitis patients, then stratified by age, sex, and calendar year of cohort entry.

Results

Compared with nonvasculitis patients, GCA patients had increased mortality during the first year following diagnosis (adjusted HR 1.51, 95% confidence interval [95% CI] 1.40–1.64), and marginally increased mortality between 1 and 5 years after the diagnosis (adjusted HR 1.16, 95% CI 1.09–1.23), but not >5 years after the diagnosis (adjusted HR 1.06, 95% CI 1.00–1.12). GCA patients diagnosed before age 65 years had the highest mortality risk during the first year following diagnosis (adjusted HR 2.32, 95% CI 1.60–3.35). The mortality risk did not differ substantially by sex or calendar year of cohort entry.

Conclusion

GCA patients had an increased risk of mortality during the period shortly after the GCA diagnosis, in particular during the first year, but no increased risk after 5 years postdiagnosis. The mortality risk differed by age with an even greater increased 1‐year mortality in those age <65 years at diagnosis, but not by sex or calendar year of cohort entry.

     

Mortality trends in rheumatoid arthritis: the role of rheumatoid factor

OBJECTIVE: We previously demonstrated a widening in the mortality gap between subjects with rheumatoid arthritis (RA) and the general population. We examined the contribution of rheumatoid factor (RF) positivity on overall mortality trends and cause-specific mortality. METHODS: A population-based RA incidence cohort (1955-1995, and aged >or= 18 yrs) was followed longitudinally until death or January 1, 2006. The underlying cause of death as coded from national mortality statistics and grouped according to ICD-9/10 chapters was used to define cause-specific mortality. Expected cause-specific mortality rates were estimated by applying the age-, sex-, and calendar-year-specific mortality rates from the general population to the RA cohort. Poisson regression was used to model the observed overall and cause-specific mortality rates according to RF status, accounting for age, sex, disease duration, and calendar year. RESULTS: A cohort of 603 subjects (73% female; mean age 58 yrs) with RA was followed for a mean of 16 years, during which 398 died. Estimated survival at 30 years after RA incidence was 26.0% in RF+ RA subjects compared to 36.0% expected (p < 0.001), while in RF- RA subjects, estimated survival was 29.1% compared to 28.3% expected (p = 0.9). The difference between the observed and the expected mortality in the RF+ RA subjects increased over time, resulting in a widening of the mortality gap, while among RF- RA subjects, observed mortality was very similar to the expected mortality over the entire time period. Among RF+ RA subjects, cause-specific mortality was higher than expected for cardiovascular [relative risk (RR) 1.50; 95% confidence interval (CI) 1.22, 1.83] and respiratory diseases [RR 3.49; 95% CI 2.51, 4.72]. Among RF- RA subjects, no significant differences were found between observed and expected cause-specific mortality. CONCLUSION: The widening in the mortality gap between RA subjects and the general population is confined to RF+ RA subjects and largely driven by cardiovascular and respiratory deaths.     

Therapeutic strategies in rheumatoid arthritis over a 40-year period

OBJECTIVE: To examine trends in therapeutic strategies and to identify the determinants of starting disease modifying antirheumatic drug (DMARD) therapy over a 40-year period in a population based inception cohort of patients with rheumatoid arthritis (RA). METHODS: A population based inception cohort was assembled from among all Rochester, Minnesota, residents aged > or = 18 years who were first diagnosed with RA (1987 American College of Rheumatology criteria) between January 1, 1955, and January 1, 1995. All subjects were followed longitudinally through their complete medical records until death, migration from Olmsted County, or date of abstraction (January 1, 2001, to January 1, 2003). Drug exposure data were collected on all DMARD and corticosteroid regimens. Time to DMARD initiation was examined using the Kaplan-Meier method. The influence of calendar time and disease characteristics on time from incidence to first DMARD therapy and the number of DMARD regimens were analyzed using Cox regression and proportional odds models, respectively. RESULTS: The study population comprised 603 patients (73% female) with a mean age of 58 years and a mean followup of 15 years. At 2 years after RA onset, 26% of patients in the 1955-74 cohort, 40% in the 1975-84 cohort, and 70% in the 1985-94 cohort had received a DMARD (log-rank p < 0.001). Age, rheumatoid factor (RF) positivity, erythrocyte sedimentation rate, large joint swelling, rheumatoid nodules, and destructive changes on radiographs were significantly associated with time to first DMARD regimen after adjustment for calendar time and sex. Patients who were older and RF positive and who did not receive CS were more likely to have received more DMARD regimens. CONCLUSION: Time to initiation of DMARD therapy has shortened markedly over the past 3-4 decades. These changes in management of early RA provide evidence for the translation of scientific evidence into clinical practice in rheumatology. Age and various disease characteristics are significantly associated with initiation and the number of DMARD regimens used. These should be considered as confounders when examining the effect of early DMARD treatment on disease progression and mortality.     

Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis

OBJECTIVE: Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years. METHODS: We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985-1990, 1990-1995, 1995-2000, 2000-2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts. RESULTS: The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease-modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy. CONCLUSION: The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.     

Tolerance and effectiveness of anti–tumor necrosis factor α therapies in elderly patients with rheumatoid arthritis: A population‐based cohort study

Objective

Limited data have been published on tolerance to and efficacy of classic or biologic disease‐modifying antirheumatic drugs in elderly patients with rheumatoid arthritis (RA). The goal of the present study was to evaluate the tolerance to and effectiveness of anti–tumor necrosis factor (anti‐TNF) agents in elderly patients (≥65 years old) with RA (ERA) in comparison with younger patients (YRA).

Methods

The Swiss Clinical Quality Management program for RA is a longitudinal population‐based cohort. All patients who had received at least 1 dose of anti‐TNF agents between January 1997 and November 2005 were included and categorized according to their age. Tolerance was assessed by analyzing discontinuation rates of anti‐TNF agents. Effectiveness of these agents was assessed by analyzing RA disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) after anti‐TNF initiation.

Results

Among 1,571 patients with RA treated with anti‐TNF agents, 344 were ≥65 years of age at treatment initiation. Drug discontinuation rates (median time 3 years) and mean change in DAS28 scores at 2 years (–0.65 versus –0.58) were identical in ERA and YRA. However, HAQ score improved significantly less in ERA (–0.02) than in YRA (–0.1) and a subsequent analysis revealed that this finding was essentially due to patients >75 years of age.

Conclusion

Age in itself should not interfere with the decision to treat elderly patients with RA with anti‐TNF agents. In a subset of patients ages >75 years, no functional improvement according to HAQ should be expected despite improvements in disease activity.     

Early rheumatoid arthritis in Latin America: Low socioeconomic status related to high disease activity at baseline

Objective

To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline.

Methods

Clinical evaluation, ethnicity, socioeconomic status (SES), 4‐variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28‐ESR, and presence of erosions.

Results

Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty‐eight percent were of low/low‐middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28‐ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low‐middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low‐middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low‐middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions.

Conclusion

We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low‐middle SES is important in determining disease activity. A more genetic‐related background for erosions is possible.