Virtual Learning and Assessment in Rheumatology Fellowship Training: Objective Structured Clinical Examination Revisited.

OBJECTIVE: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face rheumatology objective structured clinical examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies for fellows-in-training (FITs). This article describes the novel design, feasibility, and stakeholder value of a vROSCE. METHODS: Through an established collaboration of 5 rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience. RESULTS: Twenty-three rheumatology FITs from 5 institutions successfully rotated through 6 stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME core competencies. A total of 65% of FITs (15 of 23) responded to the survey, and 93% of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement. CONCLUSION: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched rheumatology FITs' education and offered collaborative learning experiences across institutions.

Virtually Speaking: The Impact of a Nationwide Synchronous and Asynchronous Learning Forum.

OBJECTIVE: To address significant disruptions in didactic education precipitated by the COVID-19 pandemic, a group of rheumatology program directors collaborated with the American College of Rheumatology to create a virtual fellows-in-training (V-FIT) program. METHODS: A working group was composed to develop the virtual didactic program comprising live virtual sessions of core curricular rheumatology topics that were recorded to permit asynchronous learning. Nationally recognized educators were invited to lead sessions to fill the void in didactic education occurring on a broad scale across US rheumatology fellowship training programs. Demographic information, live and asynchronous participation data, and feedback surveys were collected from participants in the program. RESULTS: There were 3 components to V-FIT: the Virtual Rheumatology Learning (ViRL) series, the Virtual Rheumatology Practicum (ViP), and the Virtual Rheumatology Teaching Lessons (ViTLs). The ViRL program had global impact with more than 2,000 learners from more than 55 countries. ViP provided a standardized curriculum of rheumatology topics for incoming first-year fellows. ViTLs addressed advanced and interdisciplinary rheumatic disease topics for learners at all stages. CONCLUSION: With collaboration, adaptation, and innovation, the V-FIT program not only maintained but also enhanced education for rheumatology trainees, was enriched by national and international participation, and provided standardized, broadly accessible content with interdisciplinary learning.

Associations of Socioeconomic Status With Disease Progression in African Americans With Early Rheumatoid Arthritis.

OBJECTIVE: In prior cross-sectional analyses of African American patients with rheumatoid arthritis (RA), measures of socioeconomic status (SES) were associated with clinical joint damage and poorer patient-reported outcome scores. The purpose of this study was to determine whether SES measures are associated with disease progression in a cohort of African American patients with early RA (<2 years duration). METHODS: We analyzed baseline SES and change in 60-month clinical radiographs and patient-reported outcomes data (n = 101 and 177, respectively) in individuals with early RA. SES measures were educational attainment, occupation, homeownership, household income, and block group poverty. Outcomes were based on radiographs (total erosion and joint space narrowing [JSN] scores on hands and feet) and patient-reported outcomes (pain, fatigue, disability, and learned helplessness). We used logistic regression with mixed effects accounting for study site to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Both low education and occupation status were associated with worsening pain (adjusted OR 5.86 [95% CI 3.05-11.3] and adjusted OR 2.55 [95% CI 1.54-4.21], respectively). Patients without a high-school diploma were more likely to have worsened reports of learned helplessness (OR 1.92 [95% CI 1.37-2.67]). Community measures of SES were also significantly associated with patient-reported outcomes score changes. Patients living in areas of block group poverty ≥20% were twice as likely to experience increased disability scores over 60 months of disease duration (OR 1.95 [95% CI 1.17-3.25]). We found no association between SES measures and erosion or JSN score progression. CONCLUSION: Low educational attainment and nonprofessional occupation status were associated with increased worsening of patient-reported outcomes. However, there were no corresponding increases in radiographically assessed erosion or JSN score progression.

Association of Disease Activity and Disability With Rehabilitation Utilization in African American Adults With Rheumatoid Arthritis.

OBJECTIVE: To examine the association of disease activity and disability with rehabilitation utilization in African American adults with rheumatoid arthritis (RA). METHODS: We analyzed cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR) I and CLEAR II registry. Disease activity was quantified with the Disease Activity Score in 28 joints using the C-reactive protein level. Disability was measured with the Health Assessment Questionnaire. Rehabilitation utilization was determined by self-reported recall of physical therapy or occupational therapy visits in the prior 6 months or ever. We examined the association of disease activity and disability with rehabilitation utilization using separate binary logistic regression models to estimate odds ratios and 95% confidence intervals and adjusted for potential confounders. We repeated the analyses with the sample stratified by disease duration (early RA and established RA). RESULTS: Of 1,067 participants, 14% reported utilizing rehabilitation in the prior 6 months, and 41% reported ever utilizing rehabilitation. Rehabilitation utilization in the prior 6 months was similar among those with early and established RA (12% versus 16%). A greater proportion of those with established RA reported any past rehabilitation utilization (28% versus 50%). Among those with established RA but not early RA, worse disability was associated with rehabilitation utilization in the prior 6 months. Disease activity was not associated with either outcome. CONCLUSION: Among African American adults with RA, rehabilitation utilization in the 6 months prior to assessment was low and associated with disability but not disease activity. Factors driving rehabilitation utilization are unclear.

Challenges, collaboration, and innovation in rheumatology education during the COVID-19 pandemic: leveraging new ways to teach.

The novel coronavirus disease (COVID-19) pandemic has significantly impacted the field of rheumatology, in both the delivery of clinical care and didactic education for our trainees. These changes have generated significant strain for program directors and clinical educators who have had to leverage technology and develop new systems to ensure continued trainee education and assessment. We aim to outline the impacts on formal education programs presented by these unprecedented disruptions, describe the development and deployment of online teaching, reflect on the challenges and opportunities for technology-enabled learning and use of social media for education, and give some international perspectives on impacts on postgraduate rheumatology training outside the USA. With the rapid dissolution of barriers in place during the pre-COVID-19 era, we have the opportunity to assess the efficacy of new methods of care and further integrate technology into teaching and assessment. We propose that a hybrid in-person and technology-enabled learning approach, so-called blended learning, is likely to remain the most desirable future model for supporting trainee learning.

Correction to: Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

This article has been amended to include open access.

Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

BACKGROUND: Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. PURPOSE: Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. DATA SOURCES: English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. STUDY SELECTION: Two persons independently selected studies based on predefined inclusion criteria. DATA EXTRACTION: One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. DATA SYNTHESIS: We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. LIMITATIONS: Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. CONCLUSIONS: Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. REGISTRATION: PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260 ).

Socioeconomic factors and self-reported health outcomes in African Americans with rheumatoid arthritis from the Southeastern United States: the contribution of childhood socioeconomic status.

BACKGROUND: There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. METHODS: Data originated from the cross-sectional arm of the Consortium Evaluation of African-Americans with Rheumatoid Arthritis (CLEAR II), which recruited African-Americans with RA from six sites in the Southeastern United States. We used linear regression models to evaluate associations of parental homeownership status and educational level at participant time of birth with participant-reported fatigue (Visual Analog scale, cm), pain (Visual Analog scale, cm), disability (Health Assessment Questionnaire) and helplessness (Rheumatology Attitudes Index), independently of participant homeownership status and educational level. Models included random effects to account for intra-site correlations, and were adjusted for variables identified using backward selection, from: age, disease-duration, sex, medication use, body-mass index, smoking history. RESULTS: Our sample included 516 CLEAR II participants with full data on demographics and covariates. 89% of participants were women, the mean age was 54.7 years and mean disease duration was 10.8 years. In age adjusted models, parental non-homeownership was associated with greater fatigue (ß = 0.75, 95% CI = 0.36-1.14), disability (ß = 0.12, 95% CI = 0.04-0.19) and helplessness (ß = 0.12, 95% CI = 0.03-0.21), independently of participant homeownership and education; parental education had a further small influence on self-reported fatigue (ß = 0.20, 95% CI = 0.15-0.24). CONCLUSIONS: Parental homeownership, and to a small extent parental education, had modest but meaningful relationships with self-reported health among CLEAR II participants.

Fellow As Teacher Curriculum: Improving Rheumatology Fellows' Teaching Skills During Inpatient Consultation.

OBJECTIVE: Enhancing rheumatology fellows' teaching skills in the setting of inpatient consultation may have a broad positive impact. Such efforts may improve fellows' clinical skills and overall patient care. Most importantly, effective resident-fellow teaching interactions may not only increase residents' knowledge of rheumatology but may influence their career choice. However, a number of barriers to the resident-fellow teaching interaction have been identified, including fellows' teaching skills. We developed the Fellow As Clinical Teacher (FACT) curriculum in order to enhance fellows' teaching skills during inpatient consultation. METHODS: The FACT curriculum was delivered in two 45-minute workshops during the 3-day Winter Symposium of the Carolinas Fellows Collaborative. We evaluated its effect with self-assessment surveys and fellow performance on the objective structured teaching exercise (OSTE) before and after participation in the curriculum. RESULTS: Nineteen fellows from 4 rheumatology training programs participated in the pre- and post-curriculum OSTEs and 18 fellows completed pre- and post-curriculum surveys. OSTE scores improved on 5 of the 8 items assessed, and the total OSTE score improved as well (34.7 versus 29.5; P < 0.01) after the FACT curriculum. Fellows' self-assessment of their teaching skills and intent to teach during consultation also increased after participation in the curriculum. CONCLUSION: The FACT curriculum, focused on teaching during consultation, improved fellows' teaching skills and attitudes toward teaching. Improving and increasing fellow teaching, particularly in the consultation setting, may impact patient care, resident and fellow learning, and teaching skills of future faculty, and could potentially influence residents' career choice.

Expert panel consensus on assessment checklists for a rheumatology objective structured clinical examination.

OBJECTIVE: While several regional fellowship groups conduct rheumatology objective structured clinical examinations (ROSCEs), none have been validated for use across programs. We aimed to establish agreement among subspecialty experts regarding checklist items for several ROSCE stations. METHODS: We administered a 1-round survey to assess the importance of 173 assessment checklist items for 11 possible ROSCE stations. We e-mailed the survey to 127 rheumatology educators from across the US. Participants rated each item's importance on a 5-point Likert scale (1 = not important to 5 = very important). Consensus for high importance was predefined as a lower bound of the 95% confidence interval ≥4.0. RESULTS: Twenty-five individuals (20%) completed the expert panel survey. A total of 133 of the 173 items (77%) met statistical cutoff for consensus to retain. Several items that had population means of ≥4.0 but did not meet the predetermined definition for consensus were rejected. The percentage of retained items for individual stations ranged from 24% to 100%; all items were retained for core elements of patient counseling and radiograph interpretation tasks. Only 24% of items were retained for a rehabilitation medicine station and 60% for a microscope use/synovial fluid analysis station. CONCLUSION: This single-round expert panel survey established consensus on 133 items to assess on 11 proposed ROSCE stations. The method used in this study, which can engage a diverse geographic representation and employs rigorous statistical methods to establish checklist content agreement, can be used in any medical field.

Medication risk communication during rheumatology office visits.

OBJECTIVE: We used a multidimensional framework to describe the types of information about medication risks that rheumatologists provide to rheumatoid arthritis (RA) patients during routine office visits. METHODS: We analyzed 1,094 audiotaped rheumatology office visits involving 450 RA patients. Each patient had up to 3 visits audiotaped. In conjunction with each office visit, patients also completed a self-administered questionnaire and interview and the rheumatologists provided ratings of patient health status. RESULTS: The number of medication risks discussed per visit ranged from 0-18, with a mean ± SD of 3.23 ± 2.93. The rheumatologist initiated ∼80% of the medication risk discussions. Approximately one-fourth of the discussions (25.6%) were limited to an assessment of whether or not the patient was experiencing a medication side effect. More risks were discussed during visits when changes to the patient's regimen were discussed than when no changes were discussed (X= 3.93, SD = 3.10 and X = 2.20, SD = 2.34, respectively; P < 0.0001). When medications were being proposed for addition to the patient's regimen, the most frequently discussed risk dimensions were the importance of monitoring (30%), probability (29.8%), things the patient should do to minimize risk (25.5%), and risk severity (21.8%). CONCLUSION: Most discussions of medication risks that we observed were quite limited and often restricted to an assessment of whether the patient was experiencing side effects from their current medications. The amount of information that is optimal and how to tailor information to the preferences and abilities of individual patients remain important areas for future research.

Socioeconomic disparities in the health of african americans with rheumatoid arthritis from the southeastern United States.

OBJECTIVE: To examine cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis registry for the association between socioeconomic status (SES) with clinical and self-report health outcomes. METHODS: We analyzed data on 937 African Americans who provided comprehensive sociodemographic data in addition to self-reported health outcomes. SES measures included educational attainment, homeownership, household income, and occupation. Outcomes included measures of disease activity, joint damage, autoantibody status, and self-reported measures. Multivariable linear, logistic, and zero-inflated Poisson regression models were used to estimate associations of each SES measure with rheumatoid arthritis (RA) outcomes, controlling for sex, age, disease duration, comorbid conditions, body mass index, smoking, methotrexate/leflunomide use, and biologic agent use. RESULTS: The mean age was 54 years, 86% were women, and the mean RA disease duration was 7.8 years. Approximately 24% had less than a high school degree, 56% had a nonprofessional occupation, 75% had a household income ≤$30,000, and 55% were nonhomeowners. In multivariable regression models, significantly increased associations of disease activity measures and self-reported health outcomes were observed with low household income (≤$30,000/year) and nonhomeownership. Education less than high school was primarily associated with self-reported health outcomes. Among participants with disease duration <2 years, associations of SES were confined to self-reported measures. CONCLUSION: Our results indicate significant socioeconomic disparities in self-reported physical and mental health, clinical disease activity measures, and autoantibody status among African Americans with RA not explained by differences in demographics, medication use, and health behaviors.

Complementary and alternative medicine use in African Americans with rheumatoid arthritis.

OBJECTIVE: Racial/ethnic differences with regard to complementary and alternative medicine (CAM) use have been reported in the US. However, specific details of CAM use by African Americans with rheumatoid arthritis (RA) are lacking. METHODS: Data were collected from African Americans with RA enrolled in a multicenter registry regarding the use of CAM, including food supplements, topical applications, activities, and alternative care providers. Factors associated with CAM use by sex and disease duration were assessed using t-test, Wilcoxon's rank sum test, chi-square test, and logistic regression analyses. RESULTS: Of the 855 participants, 85% were women and mean age at enrollment was 54 years. Overall, ever using any of the CAM treatments, activities, and providers was 95%, 98%, and 51%, respectively (median of 3 for number of treatments, median of 5 for activities, and median of 1 for providers). Those with longer disease duration (>2 years) were significantly more likely (odds ratio ≥2.0, P < 0.05) to use raisins soaked in vodka/gin, to take fish oils, or to drink alcoholic beverages for RA treatment than those with early disease. As compared to men, women were significantly (P < 0.05) more likely to pray/attend church, write in a journal, and use biofeedback, but were less likely to smoke tobacco or topically apply household oils for treatment of RA. CONCLUSION: CAM use was highly prevalent in this cohort, even in individuals with early disease. Health care providers need to be aware of CAM use as some treatments may potentially have interactions with conventional medicines. This could be important within this cohort of African Americans, where racial disparities are known to affect access to conventional care.

Patient-rheumatologist communication concerning prescription medications: getting to the gist.

OBJECTIVE: Fuzzy trace theory was used to develop a coding scheme that captures the gist that patients extract from information about medication risks and benefits and to explore the extent to which different patients extract different gist representations from the same information. METHODS: Data were collected from 2003-2007 in a study that included audiotape recording office visits that rheumatoid arthritis (RA) patients had with their rheumatologists. Each patient (n = 365) had up to 3 visits audiotape recorded. The audiotapes were transcribed to facilitate content analysis. Four patients with RA who did not participate in the original study guided development of the coding scheme and used it to code the transcripts. RESULTS: The coding scheme contains 14 gist themes centering on medication effectiveness, need, and safety. There was considerable variation among the gist coders in the specific themes they extracted from individual transcripts. We observed the greatest intercoder agreement for the 4 gist theme variables related to whether the rheumatologist wanted to make changes to the medication regimen. Furthermore, the coders rarely used the "not clear" category to code these 4 variables. In contrast, intercoder agreement for the remaining gist themes, which were designed to capture issues central to the communication of information about medication risks and benefits, was low and the "not clear" category was used more frequently. CONCLUSION: Our study findings suggest that different people exposed to the same information may form different gist representations. Patient-provider communication concerning medication risks and benefits might be enhanced by better understanding the factors that influence the gist extraction process.

Comparison of the disease activity score using erythrocyte sedimentation rate and C-reactive protein in African Americans with rheumatoid arthritis.

OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthritis (RA). Studies have reported discordance between DAS28 based on erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in patients with RA. However, such comparison is lacking in African Americans with RA. METHODS: This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry, which enrolls self-declared African Americans with RA. Using tender and swollen joint counts, separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient's assessment of disease activity. The scores were compared using paired t-test, simple agreement and κ, correlation coefficient, and Bland-Altman plots. RESULTS: Of the 233 included participants, 85% were women, mean age at enrollment was 52.6 years, and median disease duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher than DAS28-CRP3 (4.8 vs 3.9; p < 0.001). Similarly, mean DAS28-ESR4 was significantly higher than DAS28-CRP4 (4.7 vs 3.9; p < 0.001). ESR-based DAS28 remained higher than CRP-based DAS28 even when stratified by age, sex, and disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28-CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4 in 40% of the participants relative to DAS28-ESR4. CONCLUSION: There was significant discordance between the ESR-based and CRP-based DAS28, a situation that could affect clinical treatment decisions for African Americans with RA.

Competency-based goals, objectives, and linked evaluations for rheumatology training programs: a standardized template of learning activities from the Carolinas Fellows Collaborative.

OBJECTIVE: American Council on Graduate Medical Education program requirements mandate that rheumatology training programs have written goals, objectives, and performance evaluations for each learning activity. Since learning activities are similar across rheumatology programs, we aimed to create competency-based goals and objectives (CBGO) and evaluations that would be generalizable nationally. METHODS: Through an established collaboration of the 4 training programs' directors in North Carolina and South Carolina, we collaboratively composed CBGO and evaluations for each learning activity for rheumatology training programs. CBGO and linked evaluations were written using appropriate verbs based on Bloom's taxonomy. Draft documents were peer reviewed by faculty at the 4 institutions and by members of the American College of Rheumatology (ACR) Clinician Scholar Educator Group. RESULTS: We completed templates of CBGO for core and elective rotations and conferences. Templates detail progressive fellow performance improvement appropriate to educational level. Specific CBGO are mirrored in learning activity evaluations. Templates are easily modified to fit individual program attributes, have been successfully implemented by our 4 programs, and have proven their value in 4 residency review committee reviews. CONCLUSION: We propose adoption of these template CBGO by the ACR, with access available to all rheumatology training programs. Evaluation forms that exactly reflect stated objectives ensure that trainees are assessed using standardized measures and that trainees are aware of the learning expectations. The objectives mirrored in the evaluations closely align with the proposed milestones for internal medicine training, and will therefore be a useful starting point for creating these milestones in rheumatology.

Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans.

OBJECTIVE: To examine whether polymorphisms in genes coding for drug-metabolizing enzymes (DMEs) have an impact on rheumatoid arthritis (RA) risk due to cigarette smoking in African Americans. METHODS: Smoking status was evaluated in African American patients with RA compared with non-RA controls, with smoking exposure categorized as heavy smoker (≥10 pack-years) versus never smoker/<10 pack-years. Individuals were genotyped for a homozygous deletion polymorphism in the M1 gene loci of glutathione S-transferase (GSTM1-null) in addition to tagging single-nucleotide polymorphisms (SNPs) in N-acetyltransferase 1 (NAT1), NAT2, and epoxide hydrolase 1 (EPXH1). Associations of these genotypes with RA risk were examined using logistic regression, and gene-smoking interactions were assessed. RESULTS: There were no significant associations of any DME genotype with RA. After adjustment for multiple comparisons, there were significant additive interactions between heavy smoking and the NAT2 SNPs rs9987109 (P(additive) = 0.000003) and rs1208 (P(additive) = 0.00001); the attributable proportion due to interaction ranged from 0.61 to 0.67. None of the multiplicative gene-smoking interactions examined remained significant with regard to overall disease risk, after adjustment for multiple testing. There was no evidence of significant gene-smoking interactions in analyses of GSTM1-null, NAT1, or EPXH1. DME gene-smoking interactions were similar when cases were limited to those patients who were positive for anti-citrullinated protein antibodies. CONCLUSION: Among African Americans, RA risk imposed by heavy smoking appears to be mediated in part by genetic variation in NAT2. While further studies are needed to elucidate the mechanisms underpinning these interactions, these SNPs appear to identify African American smokers at a much higher risk for RA, in whom the relative risk is at least 2-fold higher when compared to nonsmokers lacking these risk alleles.

Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans.

OBJECTIVE: Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population. METHODS: Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles. RESULTS: Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005). CONCLUSION: The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans.

Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis.

BACKGROUND: There are no proven therapies that modify the structural changes associated with osteoarthritis (OA). Preclinical data suggests that intra-articular recombinant human BMP-7 (bone morphogenetic protein-7) has reparative effects on cartilage, as well as on symptoms of joint pain. The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7. The secondary objectives were to determine the effect on symptomatic responses through 24 weeks. METHODS: This was a Phase 1, double-blind, randomized, multi-center, placebo-controlled, single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA. Each cohort was to consist of 8 treated participants, with treatment allocation in a 3:1 active (intra-articular BMP-7) to placebo ratio. Eligible participants were persons with symptomatic radiographic knee OA over the age of 40. The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessments, immunogenicity data and radiographic assessments. Secondary objectives were to determine the proportion of participants with a 20%, 50%, and 70% improvement in the WOMAC pain and function subscales at 4, 8, 12, and 24 weeks. Other secondary outcomes included the change from baseline to 4, 8, 12, and 24 weeks for the OARSI responder criteria. RESULTS: The mean age of participants was 60 years and 73% were female. All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups. The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays. By week 12, most participants in both the BMP-7 and placebo groups experienced a 20% improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement. In the participants who received 0.1 mg and 0.3 mg BMP-7, there was a trend toward greater symptomatic improvement than placebo. The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo. CONCLUSIONS: There was no dose limiting toxicity identified in this study. The suggestion of a symptom response, together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis.