Vasculitis and peripheral neuropathy.

PURPOSE OF REVIEW: Vasculitis of medium-sized and small vessels commonly affects peripheral nerves and can occur in context of a systemic vasculitis with multiorgan involvement or a nonsystemic vasculitis limited to the peripheral nervous system. This review summarizes the clinical and pathological features of systemic and nonsystemic vasculitis of the peripheral nervous system. RECENT FINDINGS: Vasculitis of peripheral nerves is a diffuse process that affects the vasa nervorum along the entire length of affected nerves but appears to cause injury primarily in a zone in the proximal-middle of the nerve that is particularly susceptible to ischemic injury. Nerve biopsy can help establish the diagnosis of a systemic vasculitis, particularly when other organ involvement is not clinically apparent, and is required for diagnosis of nonsystemic vasculitic neuropathy. Observational studies suggest that nonsystemic vasculitic neuropathy responds to immunosuppressive therapy but conclusive data are lacking. SUMMARY: The current review summarizes the clinical and pathological features of both systemic and nonsystemic vasculitis of the peripheral nervous system so that clinicians can better recognize, make a more timely diagnosis, and thus treat this condition more effectively in their patients.

Evaluating radiocarpal cartilage matrix changes 3-months after anti-TNF treatment for rheumatoid arthritis using MR T1ρ imaging.

PURPOSE: To evaluate the feasibility of MR T1ρ in assessing radiocarpal cartilage matrix changes following rheumatoid arthritis (RA) treatment. MATERIALS AND METHODS: Five healthy controls and nine RA patients were studied: three RA patients with low disease activity that were treated with methotrexate (MTX) alone and six with active disease despite MTX treatment who were additionally treated with certolizumab pegol, an anti-tumor necrosis factor biologic. Wrist 3 Tesla MRI were acquired at baseline and 3-month follow-up. T1ρ were quantified for lunar, radius, and scaphoid cartilage. Reproducibility was evaluated using coefficients of variation (CV). Longitudinal changes were evaluated with t-test and relationships between T1ρ with clinical, MRI, and patient-reported outcomes were evaluated with Spearman's rho. RESULTS: Scan/re-scan CVs of T1ρ values were all <5%, and intra- and inter-reader CVs were all < 2.0%. Baseline scaphoid T1ρ values were significantly higher in RA patients compared with healthy controls (P = 0.032). Changes in T1ρ (baseline, 3-month) were correlated with EULAR treatment response criteria: -2.26 ± 0.75 ms, 1.08 ± 0.52 ms, and 2.18 ± 0.45 ms for good, moderate, and nonresponders, respectively. Significant correlations were found between changes in global T1ρ values and changes in DAS28-CRP (rs = 0.683; P = 0.042), MHQ (rs = -0.783; P = 0.013), and HAQ (rs = 0.833; P = 0.010). CONCLUSION: Despite the limited sample size and follow-up time points, there were significant correlations between changes in radiocarpal T1ρ and changes in disease activity as assessed by clinical and patient-reported outcomes. Our findings encourage further research into MR T1ρ assessment of RA disease activity and treatment response. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1514-1522.

High-temporospatial-resolution dynamic contrast-enhanced (DCE) wrist MRI with variable-density pseudo-random circular Cartesian undersampling (CIRCUS) acquisition: evaluation of perfusion in rheumatoid arthritis patients.

This study is to evaluate highly accelerated three-dimensional (3D) dynamic contrast-enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo-random variable-density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k-t SPARSE-SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti-tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow-up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm(3) and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28-ESR (r = -0.80, p < 0.05) and DAS28-CRP (r = -0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow-up (with DAS28-ESR r = -0.79, p < 0.05, and DAS28-CRP r = -0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses.

Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist.

PURPOSE: To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS: Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS: The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION: The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.

A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity.

OBJECTIVE: CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a loss which may play a role in the pathogenesis of this disease. We previously showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells are functionally deficient in comparison to FcRL3- Treg cells. This study was undertaken to investigate the potential role of FcRL3 in RA. METHODS: A cross-sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3 expression on T cell subsets, including Treg cells, in peripheral blood samples from 51 patients with RA enrolled in the University of California, San Francisco (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database. RESULTS: Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed higher levels of FcRL3 on Treg cells, and on CD8+ and γ/δ T cells, in comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these T cell subpopulations correlated with RA disease activity in patients harboring the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in patients with erosive RA, and the FCRL3 -169C allele was overrepresented in patients with erosive RA. CONCLUSION: Our findings indicate that FcRL3 expression, which is strongly associated with the presence of the FCRL3 -169C allele, may serve as a biomarker for RA disease activity.

Quantitative characterization of bone marrow edema pattern in rheumatoid arthritis using 3 Tesla MRI.

PURPOSE: To develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signal intensity changes, and perfusion properties. MATERIALS AND METHODS: Fourteen RA patients and three controls were scanned using 3 Tesla MR. BME was semi-automatically segmented in water images obtained from iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequences. BME perfusion parameters (enhancement and slope) were evaluated using three-dimensional (3D) dynamic enhanced MRI (DCE-MRI). Experimental reproducibility, inter- and intra-observer reproducibility of BME quantification were evaluated using root mean square coefficients of variation (RMS-CV) and intraclass correlation (ICC). RESULTS: The RMS-CV for BME volume quantification with repeated scans were 6.9%. The inter-observer ICC was 0.993 and RMS CV was 5.2%. The intra-observer ICC was 0.998 and RMS CV was 2.3%. Both maximum enhancement and slope during DCE-MRI were significantly higher in BME than in normal bone marrow (P < 0.001). No significant correlation was found between BME quantification and clinical evaluations. CONCLUSION: A highly reproducible semi-automatic method for quantifying BME lesion burden in RA was developed, which may enhance our capability of predicting disease progression and monitoring treatment response.

Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine.

OBJECTIVE: To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine. METHODS: All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase. CONCLUSION: Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine.

Levels of plasma fibrinogen are elevated in well-controlled rheumatoid arthritis.

OBJECTIVE: Patients with RA have systemic inflammation and increased risk of cardiovascular (CV) events, including thrombosis. Levels of fibrinogen, a pro-thrombotic protein with predictive value for CV disease (CVD), are elevated during systemic inflammation. We compared circulating fibrinogen levels in patients with RA with healthy controls and evaluated the relationship with measures of disease activity. METHODS: Patients with RA and controls were recruited at the University of California, San Francisco (UCSF). Disease activity was evaluated using standard composite indices. Fibrinogen, ESR, serum CRP, acute-phase serum amyloid A and levels of selected cytokines were quantified. RESULTS: A total of 105 RA patients and 62 controls were studied. Among patients with RA, disease activity ranged from quiescent to highly active disease. Circulating fibrinogen levels were significantly higher in RA than in controls [median (interquartile range) 466 (391-575) vs 367 (309-419) mg/dl, respectively, P < 0.0001]. This difference remained highly statistically significant after adjustment for demographic variables and BMI. Although fibrinogen correlated significantly with clinical measures of disease activity, significantly elevated levels were observed at low levels of activity, even in RA patients with no detectable swollen or tender joints. In multivariable models, ~ 80% of the increased fibrinogen in RA was accounted for by increases in CRP and ESR. CONCLUSION: Circulating levels of fibrinogen are elevated in RA and correlated with markers of inflammation, but only modestly correlate with clinical assessments of disease activity. Even RA patients with excellent clinical disease control exhibit elevated levels compared with controls.

Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an essential negative regulator of T cell activation. Recent evidence suggests that CTLA-4 association with the immunological synapse during contact with antigen-presenting cells is important for its inhibitory function. In the present study, we observed a direct interaction of CTLA-4 with the phosphorylated form of T cell receptor (TCR)zeta within the glycolipid-enriched microdomains associated with the T cell signaling complex. In this setting, CTLA-4 regulated the accumulation/retention of TCRzeta in the signaling complex, as the lipid raft fractions from CTLA-4KO T cells contained significantly higher amounts of the TCR components when compared with wild-type littermates. In contrast, coligation of CTLA-4 with the TCR during T cell activation selectively decreased the amount of TCRzeta that accumulated in the rafts. These results suggest that CTLA-4 functions to regulate T cell signaling by controlling TCR accumulation and/or retention within this a critical component of the immunological synapse.

Smoking Is Associated with Higher Disease Activity in Rheumatoid Arthritis: A Longitudinal Study Controlling for Time-varying Covariates.

OBJECTIVE: Prior studies around the relationship between smoking and rheumatoid arthritis (RA) disease activity have reported inconsistent findings, which may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the association between smoking and RA outcomes using statistical methods that account for time-varying confounding and loss to followup. METHODS: We included 282 individuals with an RA diagnosis using electronic health record data collected at a public hospital between 2013 and 2017. Current smoking status and disease activity were assessed at each visit; covariates included sex, race/ethnicity, age, obesity, and medication use. We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity measures at 27 months, and compared results to conventional longitudinal methods. RESULTS: Smoking was associated with an increase of 0.64 units in the patient global score compared to nonsmoking (p = 0.01), and with 2.58 more swollen joints (p < 0.001). While smoking was associated with a higher clinical disease activity score (2.11), the difference was not statistically significant (p = 0.22). We found no association between smoking and physician global score, or C-reactive protein levels, and an inverse association between smoking and tender joint count (p = 0.05). Analyses using conventional methods showed a null relationship for all outcomes. CONCLUSION: Smoking is associated with higher levels of disease activity in RA. Causal methods may be useful for investigations of additional exposures on longitudinal outcome measures in rheumatologic disease.

Structural Changes over a Short Period Are Associated with Functional Assessments in Rheumatoid Arthritis.

OBJECTIVE: To investigate the correlation between changes in radiological quantitative assessment with changes in clinical and functional assessment from baseline to 3 months in patients with rheumatoid arthritis (RA). METHODS: Twenty-eight patients with RA [methotrexate (MTX) and anti-tumor necrosis factor-α (TNF-α) group with high disease activity (n = 18); and MTX group with low disease activity (n = 10)] underwent assessments at baseline and 3 months: clinical [28-joint count Disease Activity Score (DAS28)], functional [Health Assessment Questionnaire (HAQ) and Michigan Hand Outcome Questionnaire (MHQ)], and imaging-based [3 Tesla magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT)]. MR images were evaluated semiquantitatively [RA MRI scoring (RAMRIS)] and quantitatively for the volume of synovitis and bone marrow edema (BME) lesions. Erosion volumes were measured using HR-pQCT. RESULTS: After 3 months, the anti-TNF-α group demonstrated an improvement in disease activity through DAS28, HAQ, and MHQ. MRI showed significant decreases in synovitis and BME volume for the anti-TNF-α group, and significant increases in the MTX group. HR-pQCT showed significant decreases in bone erosion volume for the anti-TNF-α group, and significant increases in the MTX group. No significance was observed using RAMRIS. Changes in synovitis, BME, and erosion volumes, but not RAMRIS, were significantly correlated with changes in DAS28, HAQ, and MHQ. CONCLUSION: Quantitative measures were more sensitive than semiquantitative grading when evaluating structural and inflammatory changes with treatment, and were associated with patient clinical and functional outcomes. Multimodality imaging with 3T MRI and HR-pQCT may provide promising biomarkers that help determine disease progression and therapy response.

Association of High Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index With Low Bone Mineral Density in Rheumatoid Arthritis.

OBJECTIVE: Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis (RA) have twice the risk of osteoporosis-related fracture than age-matched controls, the causes for which remain unknown. We investigated contributions of RA characteristics, medication use, and body composition to low bone mineral density (BMD) in patients with RA. METHODS: Data were from the Arthritis, Body Composition, and Disability Study (n = 138; 82 women, 56 men). Demographic, clinical, laboratory, and functional variables were collected at study visits. Body composition (fat, lean muscle, and BMD) was measured by dual x-ray absorptiometry. Linear regression analyses evaluated the association between predictors and femoral neck BMD. RESULTS: Average disease duration was 19 years, 70% of patients were rheumatoid factor positive, and 55% were high-positive anti-cyclic citrullinated peptide (anti-CCP). Age and high anti-CCP positivity were negatively associated with BMD after controlling for other variables (ß = -0.003 and -0.055, respectively, P < 0.05). Appendicular lean mass index (ALMI) was positively associated with BMD (ß = 0.053, P < 0.0001). In high anti-CCP positivity participants, increasing anti-CCP levels were associated with a negative linear trend in BMD (ß = -0.011, P = 0.026). CONCLUSION: High anti-CCP positivity and ALMI were strongly associated with BMD in patients with RA. The linear relationship of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI was positively associated with BMD, emphasizing the importance of this potentially modifiable risk factor. Our findings highlight the complicated interplay of RA disease-specific and functional factors and their impact on bone mass.

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS: Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS: Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION: Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.

Involvement of the Peripheral Nervous System in Polyarteritis Nodosa and Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.

Peripheral nerve involvement is common in polyarteritis nodosa and the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. The underlying mechanism is arteritis of the vasa nervorum, leading to ischemic neuropathy. The classic presentation is stepwise involvement of peripheral nerves with ongoing antecedent constitutional symptoms. This article reviews the pathologic findings, clinical syndromes, diagnosis, and treatment of ANCA-associated vasculitides.

Neurologic Manifestations of Rheumatoid Arthritis.

Neurologic manifestations of rheumatoid arthritis (RA) range in severity from mild paresthesias in the hand from carpal tunnel syndrome to sudden death due to impingement of the medulla by an eroded, vertically subluxed dens. Most neurologic complications are a consequence of articular inflammation and damage that leads to compression of adjacent structures of the central or peripheral nervous systems. Rare but serious extra-articular manifestations include inflammation of the meninges and ischemic neuropathies due to necrotizing arteritis of the vasa vasorum. Medical therapy with synthetic disease-modifying antirheumatic drugs and biological agents has diminished the incidence of serious neurologic manifestations in RA.

Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using high resolution- peripheral quantitative computed tomography.

AIM: The objectives of this study were: (i) to develop a standardized method of quantifying bone mineral density (BMD) and microarchitecture in the hand and wrist bones of patients with rheumatoid arthritis (RA) using high resolution- peripheral quantitative computed tomography (HR-pQCT); (ii) to compare quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP) subjects; and (iii) to correlate quantitative bone parameters at the distal radius with those at the metacarpal heads in RA subjects. METHODS: HR-pQCT imaging of the dominant hand and wrist was performed in 12 female RA patients. BMD and trabecular parameters for the 2-12% head region of the second and third metacarpals were calculated and compared between RA patients and healthy controls. Bone parameters were also calculated for 110 slices of the distal radius in RA patients and compared to data from controls and PM-OP women from a previous study. RESULTS: Compared to controls, RA patients had significantly decreased BMD, trabecular volume and number, and increased trabecular heterogeneity in the third metacarpal and distal radius. Significantly lower trabecular number and significantly higher ratio of outer annular trabecular BMD to inner trabecular BMD were observed in patients with RA, compared to patients with osteopenia (P < 0.05). Trabecular BMD in the third metacarpal and in the distal radius were significantly correlated (ρ = 0.918, P < 0.0001) in RA patients. CONCLUSION: This study established a standardized method for quantifying bone density and trabecular properties in the hand and wrist bones of RA patients using HR-pQCT. Deterioration of bone structure in RA patients was found comparable to that in osteopenic women, and trabecular bone loss near affected joints was found to be correlated with bone loss away from joints.

Current Assays to Determine Free 25-Hydroxyvitamin D in Serum.

The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of vitamin D status. For many years, emphasis has been on measuring total levels of 25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D as a potentially better marker of vitamin D status has arisen. Since the 1980s when the first measurements of free 25(OH)D were made, little progress has been made in the development of rapid, reliable methods to determine the levels of free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for which many assays exist. However, because of vagaries in the measurement of VDBP in particular and the assumption of a constant affinity of VDBP for the vitamin D metabolites (which has been shown to be problematic), calculated values have proved suspect. This changed a few years ago when a new immunoassay was developed to measure free 25(OH)D directly. This review examines methods for determining free 25(OH)D, the different methods used in clinical studies, and the relationships between free 25(OH)D and other vitamin D metabolites and the physiologic functions affected by vitamin D metabolites, such as bone cell activity and turnover. The review also comments on the value of assessing free 25(OH)D and the efforts to standardize the assays.

Assessment of 3-month changes in bone microstructure under anti-TNFα therapy in patients with rheumatoid arthritis using high-resolution peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Although one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Patients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively. RESULTS: Overall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R 2 = 0.558, p < 0.001; R 2 = 0.745, p < 0.001, respectively) in all patients. CONCLUSIONS: Using HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).

Use of Low-Literacy Decision Aid to Enhance Knowledge and Reduce Decisional Conflict Among a Diverse Population of Adults With Rheumatoid Arthritis: Results of a Pilot Study.

OBJECTIVE: Despite innovations in treatment of rheumatoid arthritis (RA), adherence is poor and disparities persist. Shared decision making (SDM) promotes patient engagement and enhances adherence; however, few tools support SDM in RA. Our objective was to pilot a low-literacy medication guide and decision aid to facilitate patient-clinician conversations about RA medications. METHODS: RA patients were consecutively enrolled into 1 of 3 arms: 1) control; patients received existing medication guide prior to clinic visit, 2) adapted guide prior to visit, and 3) adapted guide prior to plus decision aid during visit. Outcomes were collected immediately postvisit, at 1-week, and at 3- and 6-month interviews. Eligible adults had to have failed at least 1 disease-modifying antirheumatic drug and fulfill 1 of the following: age >65 years, immigrant, non-English speaker, less than high school education, limited health literacy, and racial/ethnic minority. Primary outcomes were knowledge of RA medications, decisional conflict, and acceptability of interventions. RESULTS: The majority of 166 patients were immigrants (66%), non-English speakers (54%), and had limited health literacy (71%). Adequate RA knowledge postvisit in arm 3 was higher (78%) than arm 1 (53%; adjusted odds ratio 2.7, 95% confidence interval 1.2, 6.1). Among patients with a medication change, there was lower (better) mean decisional conflict in arms 2 and 3 (P = 0.03). There were no significant differences in acceptability. CONCLUSION: A low-literacy medication guide and decision aid was acceptable, improved knowledge, and reduced decisional conflict among vulnerable RA patients. Enhancing knowledge and patient engagement with decision support tools may lead to medication choices better aligned with RA patients' values and preferences.