Patient, disease, and therapy-related factors that influence discontinuation of disease-modifying antirheumatic drugs: a population-based incidence cohort of patients with rheumatoid arthritis

OBJECTIVE: A major challenge in management of rheumatoid arthritis (RA) is prediction of longterm response to disease-modifying antirheumatic drug (DMARD) treatment. Our objective was to identify the predictors of DMARD discontinuation in an incidence cohort of patients with RA followed continuously from their incidence date. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota, residents aged > or = 18 years diagnosed with RA (by 1987 American College of Rheumatology criteria) from January 1, 1955, to January 1, 1995, were followed longitudinally through their complete medical records until January 1, 2001. Detailed drug exposure data were collected on all DMARD and glucocorticoid regimens. Subjects were considered exposed to a DMARD if duration of use was > or = 30 days. Time to discontinuation of DMARD was estimated using survival analysis techniques. Andersen-Gill models with multiple events per patient were used to assess the influence of demographics, calendar time, comorbidities, disease characteristics [disease duration, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), joint counts, radiographic changes, nodules, RA complications], and therapy characteristics (DMARD use, singly or in combination, glucocorticoid use, first or subsequent regimen, effect of previous therapy) on time from DMARD initiation to discontinuation. RESULTS: The study population comprised 345 DMARD-treated patients (73% female) with mean age of 53.1 years and mean followup 15.4 years. Median time taking any DMARD was 16.0 months for the first, and 17.9 months for all regimens. Methotrexate (MTX) had the longest time to discontinuation, with a median of 30.3 months without folate, and 61.7 months with folate supplementation. Among the various disease characteristics examined, only higher ESR at DMARD initiation was significantly associated with a shorter time taking DMARD [hazard ratio (HR) 1.05 per 10 mm/h increase, 95% CI 1.02, 1.08]. In multivariable Andersen-Gill models considering all DMARD regimens, hydroxychloroquine use (HR 0.77, 95% CI 0.64, 0.92) and MTX use (HR with folate 0.39, 95% CI 0.30, 0.51; HR without folate 0.51, 95% CI 0.39, 0.67) were significantly associated with longer time to DMARD discontinuation, whereas prior MTX use (HR 1.96, 95% CI 1.57, 2.45) was associated with shorter time to DMARD discontinuation, after adjusting for age, sex, calendar year, Charlson comorbidity index, disease duration, and ESR at DMARD initiation. Disease duration was negatively associated with time to DMARD discontinuation; each 10 year increase in disease duration corresponded to a 14% decrease in the risk of discontinuation (HR 0.86, 95% CI 0.75, 0.98). CONCLUSION: Longer RA disease duration does not appear to increase the risk of DMARD discontinuation. However, high disease activity (as assessed by ESR) is associated with a higher likelihood of discontinuing DMARD. MTX failure may identify a subgroup of patients who are less likely to respond to other DMARD and therefore could be considered as candidates for biological therapies.     

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.     

Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period

OBJECTIVE: To determine time trends in the epidemiology of rheumatoid arthritis (RA) in a population-based cohort. METHODS: An inception cohort of residents of Rochester, Minnesota > or = 18 years of age who first fulfilled the American College of Rheumatology 1987 criteria between January 1, 1955 and December 31, 1994 (applied retrospectively, as appropriate) was assembled and followed up until January 1, 2000. Incidence rates were estimated and were age- and sex-adjusted to the 1990 white population of the US. A birth cohort analysis was performed, and survival rates over time were examined. RESULTS: The incidence cohort comprised 609 patients, 445 (73.1%) of whom were female and 164 (26.9%) were male, with a mean age at incidence of 58.0 years. The overall age- and sex-adjusted annual incidence of RA among Rochester, Minnesota, residents > or = 18 years of age was 44.6/100,000 population (95% confidence interval 41.0-48.2). While the incidence rate fell progressively over the 4 decades of study, from 61.2/100,000 in 1955-1964, to 32.7/100,000 in 1985-1994, there were indications of cyclical trends over time. Birth cohort analysis showed diminishing incidence rates through successive cohorts following a peak in the 1880-1890 cohorts. Incidence rates increased with age until age 85, but peaked earlier in women than in men. The survival rate in RA patients was significantly lower than the expected rate in the general population (P < 0.001), and no improvement was noted over time. CONCLUSION: The secular trends demonstrated in this study population, including the progressive decline in the incidence of RA over the last 40 years, suggest that an environmental factor may play a role in the etiology of RA.     

Basic treatment of early rheumatoid arthritis. Abstaining from rheumatological care and preferring alternative medicine increase the risk of undertreatment

The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2-6.7), RF seronegativity (OR 2.6; 95% CI 1.8-3.8), no patient education (OR 2.2; CI 95% 1.5-3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0-16.8) and > or =10 years of education (OR 1.8; 95% CI 1.3-2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance.     

Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis

Objective

To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.

Methods

A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.

Results

Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).

Conclusion

Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.     

Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti-rheumatic drug initiation in the early years of biologic use in Quebec, Canada

Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis. We examined trends in use of traditional and biologic DMARDs, and non-DMARD treatments, among overall RA patients, and factors associated with DMARD initiation in the newly diagnosed RA. RA subjects identified with the Quebec administrative databases were followed between January 1, 2002, and December 31, 2008. DMARD use was characterized on November 1 of each year using cross-sectional analyses. For a subgroup of newly diagnosed subjects, we used multivariable logistic regressions to identify predictors of DMARD initiation within 12 months of diagnosis and survival analyses to appraise time to DMARD initiation. A total of 37,399 subjects were included (65.8 % ≥65 years; 70.5 % female). The percentage of subjects using any DMARDs increased over the study period from 41.4 % [95 % confidence interval (CI) 40.8–42.0] to 43.3 % (95 % CI 42.7–43.9). Among newly diagnosed RA, being followed by a rheumatologist was the strongest predictor of DMARD initiation (odds ratio 4.31; 95 % CI 3.73–4.97). Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids, or opioids, and a history of hospitalization increased the likelihood of DMARD initiation. Older age, female, higher comorbidity score, number of medical visits pre-diagnosis, care by other specialists, and the use of acetaminophen were inversely associated with DMARD initiation. The probability of any DMARD initiation at 12 months was 38.5 %. Despite the clinical practice guideline recommendations for earlier aggressive RA management, DMARD use appears to be suboptimal in Quebec.     

Basistherapie bei früher rheumatoider Arthritis

The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2–6.7), RF seronegativity (OR 2.6; 95% CI 1.8–3.8), no patient education (OR 2.2; CI 95% 1.5–3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0–16.8) and ≥10 years of education (OR 1.8; 95% CI 1.3–2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance.     

Lag time between onset of symptoms and access to rheumatology care and DMARD therapy in a cohort of patients with rheumatoid arthritis

OBJECTIVE: To study demographic and clinical variables associated with a longer delay in disease modifying antirheumatic drug (DMARD) therapy initiation in a cohort of patients with rheumatoid arthritis (RA). METHODS: We studied 527 new RA patients (74.3% female, median age at symptom onset 55 yrs) in a hospital setting who fulfilled the ACR criteria for the diagnosis of RA. Demographic, clinical, laboratory, and treatment variables were collected longitudinally into a computerized research database. Risk factors for delay in use of DMARD therapy and first evaluation by a rheumatologist were analyzed using a Cox regression model. RESULTS: The median lag time between symptom onset and first rheumatologist encounter was 17 months and between onset of symptoms and first DMARD therapy 19 months. Variables associated with longer delay to DMARD therapy were the lag time between symptom onset and first rheumatologist visit (RR 0.73, 95% CI 0.71-0.76) and years of education. Variables associated with longer delay in first visit with rheumatologist were swollen/tender joint count, age at symptom onset, home support, labor force status, marital status, and years of education. CONCLUSION: Awareness of factors associated with a longer delay in access to rheumatology care and DMARD therapy may help break down barriers that prevent their early access, irrespective of patient age, socioeconomic status, initial symptoms, or need for treatment.     

Trends in incidence and mortality in rheumatoid arthritis in Rochester,Minnesota, over a forty‐year period

Objective

To determine time trends in the epidemiology of rheumatoid arthritis (RA) in a population‐based cohort.

Methods

An inception cohort of residents of Rochester, Minnesota ≥18 years of age who first fulfilled the American College of Rheumatology 1987 criteria between January 1, 1955 and December 31, 1994 (applied retrospectively, as appropriate) was assembled and followed up until January 1, 2000. Incidence rates were estimated and were age‐ and sex‐adjusted to the 1990 white population of the US. A birth cohort analysis was performed, and survival rates over time were examined.

Results

The incidence cohort comprised 609 patients, 445 (73.1%) of whom were female and 164 (26.9%) were male, with a mean age at incidence of 58.0 years. The overall age‐ and sex‐adjusted annual incidence of RA among Rochester, Minnesota, residents ≥18 years of age was 44.6/100,000 population (95% confidence interval 41.0–48.2). While the incidence rate fell progressively over the 4 decades of study, from 61.2/100,000 in 1955–1964, to 32.7/100,000 in 1985–1994, there were indications of cyclical trends over time. Birth cohort analysis showed diminishing incidence rates through successive cohorts following a peak in the 1880–1890 cohorts. Incidence rates increased with age until age 85, but peaked earlier in women than in men. The survival rate in RA patients was significantly lower than the expected rate in the general population (P < 0.001), and no improvement was noted over time.

Conclusion

The secular trends demonstrated in this study population, including the progressive decline in the incidence of RA over the last 40 years, suggest that an environmental factor may play a role in the etiology of RA.

     

Mortality in rheumatoid arthritis: have we made an impact in 4 decades?

OBJECTIVE: To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. METHODS: Three population based prevalence cohorts of all Rochester, Minnesota, residents age > or =35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. RESULTS: Mortality was statistically significantly worse than expected for each of the cohorts (overall p<0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. CONCLUSION: The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.     

Disappointing longterm results with disease modifying antirheumatic drugs. A practice based study.

OBJECTIVE: To evaluate the longterm effectiveness of disease modifying antirheumatic drugs (DMARD) in an inception cohort of patients with rheumatoid arthritis (RA) seen by rheumatologists. METHODS: We performed a retrospective audit of the records of patients with onset of RA between January 1985 and June 1994. Charts were reviewed from the time of diagnosis to the last consult. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard regression to adjust for potential confounders. RESULTS: A total of 2296 DMARD therapies were analyzed. Roughly half were started within 2 years of disease onset. By 16 months, 50% of the DMARD therapy courses had been discontinued, and after 4.5 years 75% had been discontinued. Over all, methotrexate (MTX) had the highest probability of continuation. After roughly 3 years 50% of patients were still receiving MTX, compared to one-third of patients who received antimalarials or intramuscular gold, 30% D-penicillamine, 25% sulfasalazine, and 18% oral gold. After 6 years, when considering all DMARD together, only 20% of the therapies had not been discontinued, with no substantial differences between drugs. Toxicity from gold compounds occurred within the first 18 months of therapy and stabilized thereafter. For MTX, withdrawals due to toxicity continued throughout therapy. CONCLUSION: This is the largest observational study examining the longterm termination rates of DMARD in patients followed from the time of their initial consult. Our results confirm previous reports of short therapeutic times, even for patients treated early in the course of their disease. MTX appears to be the best drug within the first 5 years of disease. These differences, however, decrease in the longer term. It is unclear whether the results observed for MTX within the first years of therapy translate to better health status in the longer term when compared to other DMARD.     

Conventional monotherapy compared to a "sawtooth" treatment strategy in the radiographic progression of rheumatoid arthritis over the first eight years.

OBJECTIVE: To describe the treatment with disease-modifying antirheumatic drugs (DMARDs) in two inception cohorts of rheumatoid arthritis (RA) patients and to compare their radiographic outcomes. METHODS: A recent onset RA cohort was collected in Heinola in 1973-1975, and another in Jyv?skyl? in 1983-1989. The cohorts were followed up prospectively and treated with available DMARDs. The radiographic outcomes of 103 and 85 seropositive cohort patients from Heinola and Jyv?skyl? respectively were assigned Larsen scores (0-100) for their wrist, hand and foot radiographs in years 0, 1, 3, and 8, and compared with each other. RESULTS: In this study it was seen that DMARD treatment for RA became more extensive over time. The earlier cohort patients were treated with gold sodium thiomalate, chloroquine and D-penicillamine, while 8 additional DMARDs and various DMARD combinations were used for the later cohort patients. At the 8 year visit, 23%, 33%, and 2% of the Heinola patients, and 6%, 45%, and 21% of the Jyv?skyl? patients respectively were being treated with chloroquine, other single DMARDs, or DMARD combinations. Destruction in the peripheral joints remained lower in the more extensively treated cohort; from 0 to 8 years the median Larsen score increased from 1 to 25.5 and from 0 to 12 (p = 0.001) for the Heinola and the Jyv?skyl? patients, respectively. CONCLUSION: Our result supports a role of DMARDs in preventing joint destruction in RA in the long-term.     

Initiation of disease-modifying antirheumatic drug therapy in minority and disadvantaged patients with rheumatoid arthritis

OBJECTIVE: To evaluate disparities in time to initiation of disease modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) receiving care in public or private healthcare settings. METHODS: We reviewed the records of patients with RA initially seen at one of 2 rheumatology clinics: a clinic in a public county hospital providing care primarily to minority, disadvantaged, or uninsured patients, and a private clinic providing care to patients with health insurance coverage. Both clinics were affiliated with the same medical school. We determined time to initiation of DMARD or steroid therapy using Kaplan-Meier analyses and Cox regression. Time to initiation of therapy was measured from onset of disease until a therapy was prescribed (event) or the patient was seen for the first time at one of the 2 clinics (censored at index visit). Independent variables were ethnicity and clinic setting (public or private). RESULTS:One hundred eighteen new patients with RA were seen in the public setting, 167 in the private setting; 83% of the patients in the public clinic and 18% in the private setting were non-White. Survival analysis (disease duration 相似文献   

Is the incidence of rheumatoid arthritis rising?: Results from Olmsted County,Minnesota, 1955–2007

Objective

To examine trends in the incidence and prevalence of rheumatoid arthritis (RA) from 1995 to 2007.

Methods

To augment our preexisting inception cohort of patients with RA (1955–1994), we assembled a population‐based incidence cohort of individuals ≥18 years of age who first fulfilled the American College of Rheumatology 1987 criteria for the classification of RA between January 1, 1995 and December 31, 2007 and a cohort of patients with prevalent RA on January 1, 2005. Incidence and prevalence rates were estimated and were age‐and sex‐adjusted to the white population in the US in 2000. Trends in incidence rates were examined using Poisson regression methods.

Results

The 1995–2007 incidence cohort comprised 466 patients (mean age 55.6 years), 69% of whom were female and 66% of whom were rheumatoid factor positive. The overall age‐ and sex‐adjusted annual RA incidence was 40.9/100,000 population. The age‐adjusted incidence in women was 53.1/100,000 population (versus 27.7/100,000 population in men). During the period of time from 1995 to 2007, the incidence of RA increased moderately in women (P = 0.02) but not in men (P = 0.74). The increase was similar among all age groups. The overall age‐ and sex‐adjusted prevalence on January 1, 2005 was 0.72% (95% confidence interval [95% CI] 0.66, 0.77), which is an increase when compared with a prevalence of 0.62% (95% CI 0.55, 0.69) in 1995 (P < 0.001). Applying the prevalence on January 1, 2005 to the US population in 2005 showed that an estimated 1.5 million US adults were affected by RA. This is an increase from the previously reported 1.3 million adults with RA in the US.

Conclusion

The incidence of RA in women appears to have increased during the period of time from 1995 to 2007. The reasons for this recent increase are unknown, but environmental factors may play a role. A corresponding increase in the prevalence of RA was also observed.

     

Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis

OBJECTIVE: Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS: We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS: A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION: These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.     

"5D" Outcome in 52 patients with rheumatoid arthritis surviving 20 years after initial disease modifying antirheumatic drug therapy

OBJECTIVE: Evaluation of a complex and variable disease such as rheumatoid arthritis (RA) poses a challenge particularly over the medium to long term. A practical framework to evaluate clinically relevant outcomes over the long term is the "5D" approach of Fries, described in 1980. We describe the 20 year outcome in 52 survivors of a 123 patient cohort in terms of change in discomfort, disability, drug side effects, dollar costs, and deaths. METHODS: We studied 123 patients with RA allocated to their first disease modifying antirheumatic drug (DMARD) between 1977 and 1979. All were under the overall care of one physician over the 20 years and were maintained where possible taking a single DMARD. Baseline demographic variables, the Ritchie Articular Index (RAI), Lee functional index, and erythrocyte sedimentation rate (ESR) were initially recorded. The extent to which the demographic and disease variables contributed to need for joint replacement surgery was assessed. Therapies for comorbidity were also documented. RESULTS: At cohort inception mean age was 50 years, RAI was 35, and median disease duration 5.5 years. F:M ratio was 90:33; 96% of patients were positive for rheumatoid factor (RF). Initial median ESR was 55 mm/h. At 20 years, 9 patients (7% of original cohort, 14% of survivors) were lost to followup and 62 (50%) had died. In the 52 survivors RAI, a surrogate for disability, showed a significant improvement (p < 0.0001), but disability measured by Lee functional index showed a deterioration (p = 0.018); 50% underwent joint replacement surgery. Initial ESR and mean ESR over the first 10 years of followup were significantly higher in those who required surgery. Nonsteroidal antiinflammatory drug (NSAID) use declined, but at least 2 deaths and 4 renal deaths that may have been related to therapy were attributed to NSAID use. No unexpected DMARD toxicity or mortality occurred. Concomitant therapy for comorbidity, in particular for cardiovascular disease, osteoporosis, and gastrointestinal disease, increased: more than 60% were on these therapies at 20 year followup. CONCLUSION: Strategies to improve the outcome of RA in all dimensions should include: earlier referral for expert assessment; avoidance of NSAID gastrointestinal and nephrotoxicity; a more intensive effort to identify effective management of comorbidity and those likely to have a poor outcome. Such patients require sustained, intensive therapy to minimize later disability.     

Prevalence of and predictive factors for sustained disease‐modifying antirheumatic drug–free remission in rheumatoid arthritis: Results from two large early arthritis cohorts

Objective

Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease‐modifying antirheumatic drug (DMARD)–free sustained remission after treatment with conventional therapy.

Methods

Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD‐free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD‐free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis.

Results

Sustained DMARD‐free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD‐free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM‐RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti–cyclic citrullinated peptide 2 and IgM‐RF) as independent predictors.

Conclusion

Sustained DMARD‐free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD‐free remission.

     

Rheumatoid arthritis,its treatments,and the risk of tuberculosis in Quebec,Canada

Objective

To determine the risk of tuberculosis (TB) among a cohort of patients with rheumatoid arthritis (RA) in Quebec and assess whether this risk is associated with exposure to nonbiologic disease‐modifying antirheumatic drugs (DMARDs).

Methods

We studied a cohort of patients with RA identified from the Quebec provincial physician billing and hospitalization databases for 1980–2003. TB incidence rates were determined for the period 1992–2003 and compared with the general population, standardized for age and sex using the standardized incidence ratio (SIR). Conditional logistic regression was used in a nested case–control analysis to estimate the rate ratio (RR) of TB related to nonbiologic DMARD exposure during the year before the index date.

Results

Of the 24,282 patients with RA in the cohort, 50 cases of TB were identified. The standardized incidence rate was 45.8 cases per 100,000 person‐years compared with 4.2 cases per 100,000 person‐years in the general population of Quebec (SIR 10.9, 95% confidence interval [95% CI] 7.9–15.0). The adjusted RR of TB was 2.4 (95% CI 1.1–5.4) with corticosteroid use and 3.0 (95% CI 1.6–5.8) with nonbiologic DMARD use.

Conclusion

The age‐ and sex‐standardized incidence rate of TB in RA patients is 10 times that of the general population. At least some of this risk may be related to nonbiologic DMARD and corticosteroid therapies. Our data support the role of TB screening before initiation of any immunosuppressive therapy.