[Massive pancarditis-autopsy report]. / Massive Pankarditis ­ ein Autopsiebericht.

We report on a 69-year-old man suffering from chronic progressive oligoarthritis (localized in metacarpal and knee joints), which clinically was interpreted as steroid-sensitive seronegative chronic arthritis. The patient died from sudden death at the emergency department after a 4-week history of increasing cough and dyspnea (meanwhile obtaining negative testing results for SARS-CoV-2). During the autopsy, we found massive pancarditis affecting all cardiac compartments, in particular exhibiting constrictive pericarditis, myocarditis, and multivalvular endocarditis. Microscopically, interstitial myocarditis could be observed. Performing extensive molecular analyses, we detected Tropheryma whipplei in the tissue specimens of the heart, but not in various duodenal tissue probes or in the synovial membrane. Taken together, in the present case the cause of death was acute cardiac failure due to multivalvular pancarditis due to T. whipplei. Besides from classical symptoms and morphological signs, Whipple's disease may present with various features. Regarding the differential diagnosis of a chronic multisystem disorder with aspects of hitherto unknown arthralgia, Whipple's disease should be considered.

[Multiple sclerosis : a neurological dysimmune inflammatory disease]. / La sclérose en plaques : une maladie neurologique dysimmunitaire inflammatoire.

Multiple sclerosis is a central nervous system autoimmune disease of the white and grey matters. Its pathophysiology is much better well known. It results from the interaction between genetic and environmental susceptibility factors. The role of EBV virus has recently been highlighted. Imaging techniques and neuropathology knowledge allow to distinguish several distinct processes responsible for focal and more diffuse inflammation. Therapeutic advances in recent years have been considerable. Different molecules and treatment sequences can be proposed to the patient with a demonstrated positive impact on the risk of disability secondary progression. Precise follow-up is a key. It requires optimal and early use of various treatments. The therapeutic choice must be guided by obtaining stabilization of the disease, both clinically and in terms of imaging, without exposing the patient to an excessive risk of side effects. Continuous and sequential treatments are available.

: La sclérose en plaques est une maladie auto-immune du système nerveux central qui concerne la substance blanche mais aussi la substance grise. Sa physiopathologie est beaucoup mieux connue. Elle résulte de l'interaction entre des facteurs génétiques de susceptibilité et environnementaux. Le rôle du virus EBV a été récemment souligné. Les techniques d'imagerie et les connaissances de neuropathologie ont permis de distinguer plusieurs processus distincts responsables d'une inflammation focale, mais également plus diffuse. Les progrès thérapeutiques des dernières années sont considérables. Différentes molécules et séquences de traitements peuvent être proposées au patient avec un impact positif démontré sur le risque de progression secondaire du handicap. La précision du suivi est un élément clé de la prise en charge. Elle requiert une utilisation optimale, et surtout précoce, des différents traitements. Le choix thérapeutique doit être guidé par l'obtention d'une stabilisation de la maladie, tant sur le plan clinique qu'en imagerie, sans exposer le patient à un risque excessif d'effets secondaires négatifs. Des traitements continus et séquentiels sont disponibles.

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

[Multiple sclerosis : therapy update]. / Actualités thérapeutiques dans la sclérose en plaques.

Multiple sclerosis is still a severe disease potentially associated with a short- or long-term disability in young adults. Since a few years therapeutic progresses are considerable. New drugs and new therapy rationale considerably improved our knowledge and patient's care. Early treatment is a key within dedicated specialized and multidisciplinary units. Clinical and neuroradiological no evidence of disease activity (NEDA) is a goal, which is more often reached. Patient's evolution and follow-up is completely changed in recent years with more efficacy.

La sclérose en plaques (SEP) reste une maladie grave du système nerveux central (SNC), potentiellement responsable d'un handicap, physique ou non, à moyen et long termes, chez des adultes jeunes. Les progrès thérapeutiques au cours des dernières années ont été considérables grâce à l'avènement de nouvelles molécules, mais aussi, et peut-être surtout, de schémas thérapeutiques nettement plus performants. Les progrès des connaissances en immunologie ont eu un impact majeur dans ce domaine. La prise en charge précoce des patients au sein d'unités intégrées et multidisciplinaires est une étape essentielle qui permet de guider l'utilisation rationnelle des médicaments. L'obtention d'une stabilité clinique et neuroradiologique est un défi qui est, de plus en plus souvent, relevé avec un bénéfice majeur pour les patients.

Detection of deposited drill cuttings on the sea floor - A comparison between underwater hyperspectral imagery and the human eye.

We surveyed the deposition of drill cuttings on the seafloor along a transect at eight drilling locations in the south-western Barents Sea and Norwegian Sea, comparing traditional visual surveying methods and underwater hyperspectral imagery (UHI). The locations range from newly-drilled to around 30 years post-drilling. The visual assessments detected deposited drill cuttings to extend to around 150-200 m from the drilling location at recently drilled sites and generally less than 50 m at older locations. Quantitative UHI analyses of relative change in the spectral signature of the sediments with increasing distance from the drilling location mostly showed a change-over to conditions resembling undisturbed sediments at approximately similar distances as the visual assessments. Biological faunal community analyses also reflected these trends. The UHI-based detection of drill cuttings thus in general supported the results of visual assessments and potentially could be further developed as a method for automated surveying of drilling sites.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial.

OBJECTIVES: Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial. METHOD: Treatment-naïve RA patients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year. RESULTS: Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01-1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96-1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003). CONCLUSION: Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.

An update on hearing impairment in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic, autoimmune disease that present with intra-articular and extra-articular manifestations. Auditory system may be involved during the course of RA disease due to numbers of pathologies. The link between hearing impairment and RA has been discussed in the previous literature. In this study we provide an update on the clinical aspect of hearing impairment in RA. We suggest to test hearing in all newly diagnosed RA patients at diagnosis as well as regularly during the course of disease.

Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis: post-hoc explorative and validation studies based on the CIMESTRA and OPERA trials.

OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs). METHOD: Treatment-naïve patients with early RA (< 6 months' duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease Activity Score (DAS28) and conventional radiography [bilateral hands and feet at baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in baseline blood samples and during follow-up. Hypotheses regarding the biomarkers' relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and radiographic progression (change in total Sharp van der Heijde score ≥ 2) were generated in CIMESTRA and validated in OPERA, by Spearman's correlation and logistic regression analyses. RESULTS: Baseline IL-6, YKL-40, and VEGF correlated significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively, all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p < 0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the biomarkers (absolute values or change) was predictive of clinical remission or radiographic progression at 2 or 5 years in either study. CONCLUSION: Serum IL-6, serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at baseline, but did not have consistent predictive value for clinical remission or radiographic progression in two early RA RCTs.

Faecal calprotectin detects subclinical bowel inflammation and may predict treatment response in spondyloarthritis.

OBJECTIVE: Intestinal inflammation is frequent in patients with spondyloarthritis (SpA). Here, we test the validity of faecal calprotectin as a marker of intestinal inflammation in SpA patients and evaluate the response of adalimumab in patients with and without intestinal lesions. METHOD: Patients were included on the basis of active SpA with a Bath Ankylosing Spondylitis Disease Activity Index ≥ 4. After a 4 week non-steroidal anti-inflammatory drug washout period, patients were divided into two groups based on faecal calprotectin level (> 100 mg/kg, n = 15, and < 50 mg/kg, n = 15). Adalimumab 40 mg every other week was initiated. Patients with calprotectin >100 mg/kg received an additional 40 mg of adalimumab at baseline. Patients were followed with clinical examination at weeks 12, 20, and 52; magnetic resonance imaging (MRI) at weeks 0, 20, and 52; and endoscopy at weeks 0 and 20. RESULTS: The groups were similar with regard to clinical disease activity measures at baseline. Faecal calprotectin above 100 mg/kg accurately identified patients with intestinal inflammation. Twelve of the 15 patients with elevated calprotectin had bowel lesions, compared to only one patient in the control group. On MRI, the group with elevated calprotectin had more inflammation in the sacroiliac joints. Finally, the group with intestinal inflammation had a better clinical response to adalimumab, as evaluated by the Ankylosing Spondylitis Disease Activity Score. CONCLUSION: Elevated faecal calprotectin accurately identified SpA patients with bowel inflammation and more inflammation on MRI. Elevated faecal calprotectin at baseline may predict a better treatment response.

A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder.

Here we report a 12 year old male with an extreme presentation of spastic paraplegia along with autism and dysmorphisms. Whole exome sequencing identified a predicted pathogenic pair of missense variants in SPAST at the same chromosomal location, each with a different alternative allele, while a chromosome microarray identified a 1.73 Mb paternally inherited copy gain of 1q21.1q21.2 resulting in a blended phenotype of both Spastic paraplegia 4 and 1q21.1 microduplication syndrome. We believe that the extreme phenotype observed is likely caused by the presence of cells which contain only mutant SPAST, but that the viability of the patient is possible due mosaicism of mutant alleles observed in different proportions across tissues.

Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the optimized treatment algorithm in early RA (OPERA) trial.

This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/- adalimumab and to determine if HBL6months is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 (n = 90) and 12 months (n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL6months (0-6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (∆ total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/-radiographic progression (∆TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL1-year data, HBL1-year was median (interquartile range (IQR)) -1.9 (-3.3; -0.26 mg/cm2) in the MTX + placebo group and -1.8 (-3.6; 0.06) mg/cm2 in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL6months data and 2-year radiographic data, HBL6months was independently associated with ∆TSS after 2 years (ß = -0.086 (95% confidence interval = -0.15; -0.025) TSS unit/mg/cm2 increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92-1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL1-year, irrespective of adalimumab; HBL6months was independently associated with ∆TSS after 2 years.

Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA).

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.

Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA).

OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate (20 mg/week) and intra-articular triamcinolone (20 mg/ml) for 2 years. In addition, they were randomised to receive placebo adalimumab (DMARD group, n=91) or adalimumab (40 mg/every other week) (DMARD+adalimumab group, n=89) during the first year. Sulfasalazine and hydroxychloroquine were added if disease activity persisted after 3 months. During year 2, synthetic DMARDs continued. Adalimumab was (re)initiated if active disease reoccurred. Clinical response, remission, disability, quality of life and radiographic changes were assessed. RESULTS: One year after adalimumab withdrawal, treatment profiles and clinical responses did not differ between groups. In the DMARD/DMARD+adalimumab groups, the median 2-year methotrexate dose was 20/20 mg/week (p=0.45), triple DMARD therapy had been initiated in 33/27 patients (p=0.49), adalimumab was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were DAS28CRP<2.6:69%/66%; Clinical Disease Activity Index ≤2.8:55%/57%; Simplified Disease Activity Index <3.3:54%/49%; American College of Rheumatology/European League against Rheumatism (28 joints):44%/45% (p=0.66-1.00). Radiographic progression (Δtotal Sharp score/year) was similar 1.31/0.53 (p=0.12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy in eRA provided excellent 2-year clinical and radiographic disease control independent of adalimumab induction therapy. ES progression was slightly less during and following adalimumab induction therapy. TRIAL REGISTRATION NUMBER: NCT00660647.

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

Level of Adherence to Prophylactic Osteoporosis Medication amongst Patients with Polymyalgia Rheumatica and Giant Cell Arteritis: A Cross-Sectional Study.

Objective. To estimate level of adherence to oral calcium and vitamin D supplementation as well as bisphosphonate amongst patients with PMR and GCA treated with glucocorticoids. Method. A total of 138 patients with the diagnosis of PMR and/or GCA registered in our department in December 2013. In this cross-sectional study we interviewed all the patients to measure level of adherence to calcium and vitamin D, as well as bisphosphonates. Results. Out of the 118 included patients, 88.9% of them were adherent to their prescription. Only 2 patients (1.7%) did not take calcium and vitamin D at all and 10 patients (8.5%) took their medication infrequently, 9 and 1 out of 10 patients took the medication 50-100% of the time and less than 50% of the prescribed dose, respectively. Sixty-one patients received additional treatment with bisphosphonate and 96.6% were adherent to this therapy. The remaining 3.4% of the patients did not take the medication at all. Forgetfulness, adverse side effects, and lack of understanding of treatment benefits were the most significant causes for nonadherence to calcium and vitamin D. Conclusions. Contrary to what we expected this study found that adherence to osteoporosis preventive medication in patients with PMR and GCA was high.

Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis.

OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.