A theory-based intervention to promote medication adherence in patients with rheumatoid arthritis: a randomized controlled trial

Introduction/objectives: Adherence to prescribed medication regimens is fundamental to the improvement and maintenance of the health of patients with rheumatoid arthritis. It is therefore important that interventions are developed to address this important health behavior issue. The aim of the present study was to design and evaluate a theory-based intervention to improve the medication adherence (primary outcome) among rheumatoid arthritis patients. Methods: The study adopted a pre-registered randomized controlled trial design. Rheumatoid arthritis patients were recruited from two University teaching hospitals in Qazvin, Iran from June 2018 to May 2019 and randomly assigned to either an intervention group (n = 100) or a treatment-as-usual group (n = 100). The intervention group received a theory-based intervention designed based on the theoretical underpinnings of the health action process approach (HAPA). More specifically, action planning (making detailed plans to follow medication regimen), coping planning (constructing plans to overcome potential obstacles that may arise in medication adherence), and self-monitoring (using a calendar to record medication adherence) of the HAPA has been used for the treatment. The treatment-as-usual group received standard care. Results: Data analysis was conducted based on the principle of intention to treat. Using a linear mixed-effects model (adjusted for age, sex, medication prescribed, and body mass index), the results showed improved medication adherence scores in the intervention group (loss to follow-up = 16) compared to the treatment-as-usual group (loss to follow-up = 12) at the 3-month (coefficient = 3.9; SE = 0.8) and 6-month (coefficient = 4.5; SE = 0.8) follow-up. Intervention effects on medication adherence scores were found to be mediated by some of the theory-based HAPA variables that guided the study. Conclusion: The results of the present study support the use of a theory-based intervention for improving medication adherence among rheumatoid arthritis patients, a group at-risk of not adhering to medication regimens

Caucasian and Asian Specific Rheumatoid Arthritis Risk Loci Reveal Limited Replication and Apparent Allelic Heterogeneity in North Indians

Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations. To evaluate the transferability status of these findings to an ethnically diverse north Indian population, we performed a replication analysis. We investigated the association of 47 single-nucleotide polymorphisms (SNPs) at 43 of these genes/loci with RA in a north Indian cohort comprising 983 RA cases and 1007 age and gender matched controls. Genotyping was done using Infinium human 660w-quad. Association analysis by chi-square test implemented in plink was carried out in two steps. Firstly, association of the index or surrogate SNP (r2>0.8, calculated from reference GIH Hap-Map population) was tested. In the second step, evidence for allelic/locus heterogeneity at aforementioned genes/loci was assessed for by testing additional flanking SNPs in linkage equilibrium with index/surrogate marker

Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis

Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations

Factors predicting pain and early discontinuation of tumour necrosis factor-α-inhibitors in people with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register

Background: We examined pain levels in 2 cohorts assembled from the British Society for Rheumatology Biologics Register (BSRBR), and investigated which factors predicted Bodily Pain scores and discontinuation of TNFα-inhibitors. Method: Data were retrieved from BSRBR-RA databases for up to 1 year after commencing TNFα-inhibitors (n=11995) or being treated with non-biologic therapies (n=3632). Bodily Pain scores were derived from the Short Form-36 (SF36) questionnaire and norm-transformed to allow comparison with UK population averages. Discontinuation data were from physician reports. Other data, including 28-joint disease activity score (DAS28) measurements, were from clinical examination, interview, medical records and self-report questionnaires. DAS28-P was derived as the proportion of DAS28 attributed to patient-reported factors (tender joint count and visual analogue score). Missing baseline variables from both cohorts were imputed into 20 replicate datasets. Odds ratios (OR) and adjusted OR were calculated for higher than median pain within each cohort. Results: Participants reported moderate to severe pain at baseline, and pain scores remained >1SD worse than normal population standards at 1 year, even when disease activity responded to treatment. Baseline pain was associated with DAS28-P, worse physical function, worse mental health, and DAS28. After logistic regression, independent predictors of higher than median pain at follow up were baseline Bodily Pain score, higher DAS28-P, worse physical function or mental health and co-morbidities. Higher age, male gender, and higher BMI were additional independent predictors of higher pain in participants who received TNFα-inhibitors. Baseline pain was also one of the predictors of discontinuation of the first TNFα-inhibitor within 1 year, as were female gender, current smoking, co-morbidities, extra-articular manifestations and worse function. Conclusion: Pain persists in people with treated RA, even in those for whom inflammation responds to treatment. Worse pain outcomes are predicted by factors different to those typically found to predict inflammatory disease activity in other studies. Worse pain at baseline also predicts discontinuation of TNFα-inhibitors. Improved pain management should complement inflammatory disease suppression in RA

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ∼1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p = 2.4×10−28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations

Single nucleotide polymorphisms at the TRAF1/C5 locus are associated with rheumatoid arthritis in a Han Chinese population

<p>Abstract</p> <p>Background</p> <p>Genetic variants in <it>TRAF1C5 </it>and <it>PTPN22 </it>genes have been shown to be significantly associated with arthritis rheumatoid in Caucasian populations. This study investigated the association between single nucleotide polymorphisms (SNPs) in <it>TRAF1/C5 </it>and <it>PTPN22 </it>genes and rheumatoid arthritis (RA) in a Han Chinese population. We genotyped SNPs rs3761847 and rs7021206 at the <it>TRAF1/C5 </it>locus and rs2476601 SNP in the <it>PTPN22 </it>gene in a Han Chinese cohort composed of 576 patients with RA and 689 controls. The concentrations of anti-cyclic citrullinated peptide antibodies (CCP) and rheumatoid factor (RF) were determined for all affected patients. The difference between the cases and the controls was compared using <it>χ</it>²analysis.</p> <p>Results</p> <p>Significant differences in SNPs rs3761847 and rs7021206 at <it>TRAF1/C5 </it>were observed between the case and control groups in this cohort; the allelic p-value was 0.0018 with an odds ratio of 1.28 for rs3761847 and 0.005 with an odds ratio of 1.27 for rs7021206. This significant association between rs3761847 and RA was independent of the concentrations of anti-CCP and RF. No polymorphism of rs2476601 was observed in this cohort.</p> <p>Conclusions</p> <p>We first demonstrated that genetic variants at the <it>TRAF1/C5 </it>locus are significantly associated with RA in Han Chinese, suggesting that <it>TRAF1/C5 </it>may play a role in the development of RA in this population, which expands the pathogenesis role of <it>TRAF1/C5 </it>in a different ethnicity.</p

Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis

BACKGROUND: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. METHODOLOGY: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. PRINCIPAL FINDINGS: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORgammaT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-gamma. CONCLUSION: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype

Oral health of Chinese people with systemic sclerosis

The aim was to study oral health status, salivary function, and oral features of Chinese people with Systemic Sclerosis (SSc). Chinese people with SSc attending a university specialist clinic were invited for a questionnaire survey and a clinical examination. Ethics approval was sought (UW 08-305). Gender- and age-matched individuals without SSc who attended a university dental hospital were recruited for comparison. Forty-two SSc patients with a mean age of 54.0 ± 12.2 were examined. This study found no Chinese people with systemic sclerosis were periodontally healthy and many (76%) had periodontal pockets despite most of them (93%) practiced daily tooth-brushing. They all had caries experience (DMFT = 10.5) and many (65%) had untreated decay. Mucosal telangiectasia was a common oral feature (80%). They had lower resting salivary flow rates (0.18 ± 0.17 ml/min vs. 0.31 ± 0.21 ml/min; p = 0.003) and pH values (6.90 ± 0.40 vs. 7.28 ± 0.31; p < 0.001) and reduced maximal mouth opening (40.1 ± 6.5 mm vs. 43.6 ± 7.0 mm) than people without SSc