Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial

BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815

Adenocarcinoma arising in a cystic duplication of the small bowel: case report and review of literature

Enteric duplications are rare, but can occur anywhere along the digestive tract. Most of the patients become symptomatic in early childhood and only a few cases of adult patients have been reported in literature. Here we report a unique case of an adenocarcinoma arising in a coincidentally found cystic duplication of the small bowel

Breast MRI: guidelines from the European Society of Breast Imaging

The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)

Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials

Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem.In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica.Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles.This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption

OP0104 RHEUMATOID FACTOR, ANTI-CITRULLINATED PEPTIDE ANTIBODIES, AND SHARED EPITOPE AS PREDICTORS OF CLINICAL RESPONSE TO TREATMENT IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: A STUDY BASED ON A RANDOMIZED CONTROLLED TRIAL (NORD-STAR)

Background: Previous studies have suggested that rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) positivity selectively associates with better responses to abatacept treatment in early rheumatoid arthritis (RA). Objectives: To investigate whether RF, ACPA, and shared epitope (SE) alone or in combination predict treatment response to the initial treatment with abatacept as well as with certolizumab-pegol or tocilizumab versus active conventional treatment. Methods: This analysis included treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial to receive methotrexate in combination with active conventional treatment, certolizumab-pegol, abatacept or tocilizumab [1, 2]. ACPA positivity was defined as a concentration greater than 10 U/mL using the CCP2 EliA (Phadia), and RF positivity was defined as greater than 5 IU/mL using the IgM RF EliA (Phadia). Participants were genotyped for HLA-DRB1 alleles and classified as SE positive (≥1 SE allele) or SE-negative (no SE alleles). Clinical Disease Activity Index remission (CDAI ≤2.8) was analyzed longitudinally (4, 8, 12, 16, 24, 32, 40 and 48 weeks) with logistic generalized estimating equations (GEE) analysis. The treatment effect across subgroups, based on RF, ACPA and SE status individually and in combinations, were assessed with interaction terms, using active conventional treatment as the reference. Analyses were adjusted for sex, country, age, BMI, DAS28-CRP and smoking status at baseline. The treatment effects were analyzed after 24 and 48 weeks. Results are presented as adjusted average marginal differences in CDAI remission rates with 95% CIs. Results: A total of 812 patients underwent randomization, whereof 795 were in the primary analysis population [1, 2]. Of the 795 patients, serum samples were available for 770 patients and whole blood samples for 703 patients. Overall, 604/770 (78%) were RF positive, 633/770 (82%) were ACPA positive, 554/703 (79%) were shared epitope positive, and 431/695 (62%) were positive for all three biomarkers. At baseline, measures of disease activity were lower in seropositive (positive for either RF, ACPA or both) compared with seronegative patients. Patient characteristics stratified by treatment group are shown in Table 1. Table 2 shows the adjusted marginal differences in CDAI remission rates. With active conventional treatment as the reference, RF and/or ACPA positivity at baseline predicted a better response to abatacept at 24 weeks but not at 48 weeks. Combining RF/ACPA with SE did not yield better prediction (p interaction =0.86; p interaction =0.75, respectively). Efficacy in triple-positive patients was similar at 24 weeks and at 48 weeks in the certolizumab-pegol treatment group (p interaction =0.27; p interaction =0.27, respectively), while significantly poorer efficacy was observed at 24 weeks, but not at 48 weeks in the tocilizumab treatment group (p interaction =0.03; p interaction =0.31, respectively). Thus, at 48 weeks we found no evidence of heterogeneity of treatment effect based on RF, ACPA, and SE status individually or in combination in any of the biologic treatment groups compared with active conventional treatment. Conclusion: Based on this large randomized controlled trial, we confirm that rheumatoid factor and/or ACPA positivity are associated with a better response to abatacept at 24 weeks. However, there was no association with response at 48 weeks, and the addition of SE did not improve prediction of response. Moreover, ACPA, RF and shared epitope did not, alone or in combination, predict clinical responses of importance in any of the treatment groups. REFERENCES: [1] Hetland ML et al, BMJ 2020;371:m4328. [2] Østergaard M et al, Annals of the Rheumatic Diseases 2023;82:1286-1295. Acknowledgements: We express our gratitude to the patients, study nurses, investigators, joint assessors, data management, and study teams who were involved in the NORD-STAR trial. Disclosure of Interests: Kristina Lend: None declared, Gertjan Wolbink: None declared, Theo Rispens Novartis, Genmab, Leonid Padyukov: None declared, Giulia Frazzei: None declared, Jeroen Christiaans: None declared, Jon Lampa: None declared, Merete Lund Hetland Medac, Novartis, Pfizer, Sandoz, AbbVie, BMS, Eli Lilly, MSD, Pfizer, Sandoz, Novartis, Marte S Heiberg: None declared, Dan Nordström Pfizer, Novartis, BMS, Lilly, MSD, Novartis, Pfizer, UCB, MSD, Michael Nurmohamed: None declared, Anna Rudin: None declared, Mikkel Østergaard AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, AbbVie, Amgen Inc., BMS, Merck, Celgene, and Novartis, Espen A Haavardsholm Abbvie, Pfizer, Eli Lilly, UCB Pharma, Novartis, Kim Hørslev-Petersen: None declared, Till Uhlig Galapagos, Pfizer, UCB, Lilly, Bjorn Gudbjornsson Novartis and Nordic-Pharma, Novartis, Gerdur Grondal: None declared, Jos W.R. Twisk: None declared, Ronald F. van Vollenhoven AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB