Skeletal health among African Americans with recent‐onset rheumatoid arthritis

Objective

African Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment.

Methods

Risk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10‐year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing.

Results

Participants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3–86%, depending on age and body mass index (BMI). Ten‐year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55–69 years of age with low/normal BMI, and in those ≥70 years of age with BMI ≥30 kg/m².

Conclusion

A high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low‐risk patients accurately. Systematic application of FRAX to screen high‐risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.     

Associations of cigarette smoking with rheumatoid arthritis in African Americans

Objective

To examine the associations of cigarette smoking with rheumatoid arthritis (RA) in African Americans, and to determine whether this association is impacted by the HLA–DRB1 shared epitope (SE).

Methods

Smoking status, cumulative smoking exposure, and SE status were determined in African American patients with RA and African American healthy controls. Associations of smoking with RA were examined using age‐ and sex‐adjusted logistic regression analyses. Additive and multiplicative SE–smoking interactions were examined.

Results

After adjustment for age and sex, ever smoking (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.07, 1.97) and current smoking (OR 1.56, 95% CI 1.07, 2.26), relative to never smoking, were more common in African American patients with RA (n = 605) than in controls (n = 255). The association of smoking with RA was limited to those with a cumulative exposure exceeding 10 pack‐years, associations that were evident both in autoantibody‐positive and in autoantibody‐negative disease. There was evidence of a significant additive interaction between SE status and heavy smoking (≥10 pack‐years) in relation to RA risk (attributable proportion [AP] due to interaction 0.58, P = 0.007), with similar results for the additive interaction between SE status and ever smoking (AP 0.47, P = 0.006). There was no evidence of multiplicative interactions.

Conclusion

Among African Americans, cigarette smoking is associated not only with the risk of autoantibody‐positive RA but also with the risk of autoantibody‐negative disease. The risk of RA attributable to smoking is limited to African Americans with more than 10 pack‐years of exposure and is more pronounced among individuals positive for the HLA–DRB1 SE.

     

Factors associated with continued employment among patients with rheumatoid arthritis: a survival model.

OBJECTIVE: To evaluate the association of demographic, disease, workplace, social, and household factors with the ability of patients with rheumatoid arthritis (RA) to remain employed over time. METHODS: Four hundred seventy-two employed patients with RA recruited from a national sample of rheumatology practices were followed. Patients were interviewed once a year by telephone for 9 years and patients' physicians provided data on clinical aspects such as disease stage, joint deformity, and flares. A proportional hazards survival model based on stepwise variable selection was developed to investigate the association between continuance of work over a 9 year period and demographic, work, attitudinal, disease, and social support variables. RESULTS: In the univariate analysis, the significant factors associated with longer work survival were being younger, being self-employed, having a higher prestige occupation, working more hours per week, having higher education level, and missing fewer days of work during the baseline year. The final multivariate model included age, type of occupation and number of days missed from work as a time varying co-variate. CONCLUSION: Ability to remain employed over the 9 year study was more strongly associated with age, work characteristics, and time lost from work than with disease factors. The underlying mechanisms related to occupational prestige as a predictor of work survival should be investigated in order to develop interventions to reduce the risk of work disability.     

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.     

Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: A systematic review

Objectives

To identify factors associated with adherence to medication for rheumatoid arthritis or undifferentiated inflammatory arthritis using a systematic literature search.

Methods

PubMed, PsycINFO, EMbase and CINAHL databases were systematically searched from inception to February 2011. Articles were included if they addressed medication adherence, used a reproducible definition, determinants and its statistical relationship. Methodological quality was assessed using a quality assessment list for observational studies derived from recommendations from Sanderson et al. (2007) [12]. Resulting factors were interpreted using the Health Belief Model (HBM).

Results

18 out of 1479 identified studies fulfilled the inclusion criteria. 64 factors were identified and grouped according to the HBM into demographic and psychosocial characteristics, cues to action and perceived benefits versus perceived barriers. The belief that the medication is necessary and DMARD use prior to the use of anti-TNF had strong evidence for a positive association with adherence. There is limited evidence for positive associations between adherence and race other than White, general cognition, satisfactory contact with the healthcare provider and the provision of adequate information from the healthcare provider. There is limited evidence for negative associations between adherence and having HMO insurance, weekly costs of TNF-I, having a busy lifestyle, receiving contradictory information or delivery of information in an insensitive manner by the rheumatologist. 18 factors were unrelated to adherence.

Conclusions

The strongest relation with adherence is found to be prior use of DMARDs before using anti-TNF and beliefs about the necessity of the medication. Because the last one is modifiable, this provides hope to improve adherence.     

Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis

Summary The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck-Gesellschaft, and coordinated by the Max-Planck-Institut für Biochemie, München. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-) or placebo. In the IFN- group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN- group with an error probability of 1%. IFN- was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN- group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups.     

The HLA-DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture

OBJECTIVE: To determine whether shared epitope (SE)-containing HLA-DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population. METHODS: In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry. RESULTS: The frequency of SE-containing HLA-DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA-DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody-positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody-negative RA (P = 0.01, by chi-square test). CONCLUSION: HLA-DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which approximately 50-70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.     

Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis

Objective

To estimate the incidence and risk factors for gastrointestinal (GI) perforation among patients with rheumatoid arthritis (RA).

Methods

Claims from employer health insurance plans were used to identify RA patients and those hospitalized for upper or lower GI perforation. GI perforation cases were identified using both a sensitive and a specific definition. A Cox model using fixed and time‐varying covariates was used to evaluate the risk of GI perforation.

Results

Among 143,433 RA patients, and using a maximally sensitive GI perforation definition, 696 hospitalizations with perforation were identified. The rate of perforation was 1.70 per 1,000 person years (PYs; 95% confidence interval [95% CI] 1.58–1.83), and most perforations (83%) occurred in the lower GI tract. The rate of perforation was lower when a more specific GI perforation definition was used (0.87; 95% CI 0.78–0.96 per 1,000 PYs). Age and diverticulitis were among the strongest risk factors for perforation (diverticulitis hazard ratio [HR] 14.5 [95% CI 11.8–17.7] for the more sensitive definition, HR 3.9 [95% CI 2.5–5.9] for the more specific definition). Among various RA medication groups and compared to methotrexate, the risk of GI perforation was highest among patients with exposure to nonsteroidal antiinflammatory drugs (NSAIDs), concomitant nonbiologic disease‐modifying antirheumatic drugs, and glucocorticoids. Biologic agents without glucocorticoid exposure were not a risk factor for perforation.

Conclusion

GI perforation is a rare but serious condition that affects patients with RA, most frequently in the lower GI tract. Clinicians should be aware of risk factors for GI perforation when managing RA patients, including age, history of diverticulitis, and use of glucocorticoids or NSAIDs.     

The effect of the Arthritis Self-Management Program on outcome in African Americans with rheumatoid arthritis served by a public hospital

The purpose of the study was to determine the effect of the Arthritis Self-Management Program (ASMP) on a cohort of patients, primarily African American (90 %), with rheumatoid arthritis (RA) served by a public hospital. One hundred four patients were randomly assigned to the ASMP group or the usual care group and followed for 18 months. The primary endpoint was clinical improvement indicated by the American College of Rheumatology (ACR20). Focus groups were conducted to provide contextual data. The percentages of patients achieving ACR20 were similar in the ASMP (14 % at 18 months) and usual care (17 %) groups (p?=?0.3). However, 28 % of the 25 ASMP patients that attended four or more classes achieved ACR 20 after 18 months of follow-up, but only 5 % of the 27 ASMP patients that attended less than four classes achieved ACR20 (P?=?0.1). There was a reduction in the tender and swollen joints in both groups over time (P?=?0.02), and those aged 60 and over had fewer joints involved. Half of the cohort fell at or below the poverty level. The percentages of patients achieving ACR20 were similar in the ASMP and usual care groups. Patients who attended four or more ASMP classes improved the most, but included only half of those assigned to ASMP. This suggests a need for innovative participant retention strategies or a different type of self-management program for this population.     

Factors associated with depression and suicidal ideation among individuals with arthritis or rheumatism: Findings from a representative community survey

Objective

To investigate factors associated with depression and suicidal ideation among individuals with arthritis or rheumatism.

Methods

The nationally representative Canadian Community Health Survey 2000–2001 included 130,880 respondents (response rate 84.7%). Respondents were diagnosed as depressed using a subset of items from the Composite International Diagnostic Interview. There were 23,405 respondents age ≥20 years who reported that they had been diagnosed with arthritis or rheumatism by a health professional. Logistic regression analyses were conducted to investigate depression and suicidal ideation.

Results

One in 10 Canadians with arthritis had clinically relevant levels of major depression. The age‐ and sex‐adjusted odds ratios (ORs) of major depression (OR 2.24, 95% confidence interval [95% CI] 2.11–2.38) and suicidal ideation (OR 2.01, 95% CI 1.75–2.31) among those with arthritis were approximately twice that of those without arthritis. The adjusted ORs of major depression among those with arthritis were significantly higher among women, the unmarried, younger, and poorer individuals. Individuals in pain, with limitations in activities of daily living, with limitations in instrumental activities of daily living, and with greater numbers of chronic conditions had higher odds of major depression. Less than half of those with major depression had consulted a mental health professional. One in 5 individuals with arthritis and major depression had been suicidal in the past year.

Conclusion

The majority of individuals with arthritis and major depression were not receiving adequate treatment for major depression. Clients should be screened for major depression and suicidal ideation, particularly if they fall into the identified vulnerable groups.     

A clinical trial of specialist footwear for patients with rheumatoid arthritis

OBJECTIVES: The structural and functional changes in the RA foot often affect the patient's gait and mobility, impacting on the patient's quality of life. Successful management of these foot pathologies and resultant problems can involve the provision of specialist therapeutic footwear. The aim of the study was to evaluate the value of a new footwear design based on patients' opinions compared with a traditional footwear design. METHOD: A total of 80 patients with RA of 5 yrs or more duration, foot deformity, difficulty in being able to obtain suitable retail footwear and self-reported foot pain were recruited. Patients were randomly assigned to either an intervention group (new design) or the control group (traditional design). Patients completed two specific health-related quality of life scales (Foot Health Status Questionnaire and the Foot Function Index) at baseline and after 12 weeks. RESULTS: Only 36 patients completed the trial. Ten refused the footwear outright and 34 withdrew from the study after the footwear was supplied, due to either non-footwear related problems or reasons related to the footwear. Both the specific health-related quality of life scales demonstrated significant improvement from baseline to week 12 with the intervention group (P < 0.05). There was no significant difference in both specific health-related quality of life scales after week 12 with the traditional group (P > 0.05). CONCLUSIONS: Improvement in pain and patient satisfaction with the new design of footwear for patients with RA over the traditional design indicates the importance of patient involvement in the design process and throughout the process of supplying and monitoring the footwear. The fact that the new-design shoe was based on patients' involvement in the design process in a previous study may be the most important factor in its success. In order to meet the clinical goals of this footwear the patients need to wear them, and to achieve this the patients' requirements need to be acknowledged.     

Results of a phase-II clinical trial on treatment of rheumatoid arthritis with recombinant interferon-gamma

Summary In an open, non-randomized clinical trial conducted at multiple centres, 49 patients with rheumatoid arthritis were treated with recombinant interferon-gamma for 20 days. The study was carried out in two sub-studies. In the first, the total daily dose of interferon-gamma was 50 g; in the second, 100 g. Of the 49 cases, 40 were evaluable for statistical analysis; 24 of these patients (60%) responded to therapy, according to the criteria of a successful outcome laid down in the study protocol, and were classified as responders. In responders, the clinical parameters investigated improved with both dosages. The lower dosage differed from the higher one in having a markedly lower incidence of side-effects. The results lead to the conclusion that a randomized double-blind phase-III clinical trial should be performed.     

The HLA–DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture

Objective

To determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome‐wide) genetic admixture from the European population.

Methods

In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti–cyclic citrullinated peptide (anti‐CCP) antibodies and HLA–DRB1 genotyping, a panel of >1,200 ancestry‐informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry.

Results

The frequency of SE‐containing HLA–DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE‐containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE‐containing HLA–DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti‐CCP antibody: 86 (48.9%) of 176 patients with anti‐CCP antibody–positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti‐CCP antibody–negative RA (P = 0.01, by chi‐square test).

Conclusion

HLA–DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which ∼50–70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti‐CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.

     

Informed consent in a clinical trial of a novel treatment for rheumatoid arthritis

OBJECTIVE: To evaluate the informed consent process for a clinical trial of intravenous doxycycline for rheumatoid arthritis. METHODS: Participants completed a self-administered questionnaire about the consent process at baseline and 16 weeks following enrollment in a clinical trial. RESULTS: Respondents (n = 30) affirmed voluntary participation in the parent trial. Participants acknowledged hope and altruism as reasons for entering the trial more than expectation of personal benefit or outside influences. Many respondents did not understand randomization (14/30), placebos (15/30), or risks of study medications; 11/30 respondents believed that the study drug was completely safe. CONCLUSION: Respondents generally understood the experimental nature of the trial and confirmed their participation was voluntary. However, gaps existed in participants understanding of trial design, raising the question of whether they were adequately informed about the research study prior to enrollment. Further education of potential participants in clinical trials may be required to achieve valid informed consent.