/pdf/european-evidence-based-consensus-on-the-prevention-2i61racmdl.pdf

European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease.

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

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Sarcopenia: Its assessment, etiology, pathogenesis, consequences and future perspectives

As in previous years, the consensus group to consider the use of biological agents in the treatment of rheumatic diseases met during the 13th Annual Workshop on Advances in Targeted Therapies in April, 2011. The group consisted of rheumatologists from a number of universities among the continents of Europe, North America, South America, Australia and Asia.

Pharmaceutical industry support was obtained from a number of companies for the annual workshop itself, but these companies had no part in the decisions about the specific programme or about the academic participants at this conference. Representatives of the supporting sponsors participated in the initial working groups to supply factual information. The sponsors did not participate in the drafting of the consensus statement.

This consensus was prepared from the perspective of the treating physician.

In view of the new data for abatacept, B cell-specific agents, interleukin 1 (IL-1) antagonists, tocilizumab (TCZ) and tumour necrosis factor α blocking agents (TNF inhibitors), an update of the previous consensus statement is appropriate. To allow ease of updating, the 2010 (data from March 2009 to January 2010) updates are incorporated into the body of the article, while 2011 updates (February 2010–January 2011) are separated and highlighted. The consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 1.1 We have modified the Shekelle annotation by designating all abstracts as ‘category D evidence’, whether they describe well-controlled trials or not, as details of the study were often not available in the abstracts. Further, the number of possible references has become so large that reviews are sometimes included; if they contain category A references, they will be referred to as category A evidence.

The rheumatologists and bioscientists who attended …

https://ard.bmj.com/content/annrheumdis/72/suppl_2/ii2.full.pdf

Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2010

Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent. Although no malignancy signals have been identified to date, long-term follow-up and further research are needed to understand the risk of malignancy associated with these compounds. As is the case for biologic agents, vaccination is important to mitigate the risks of these emerging therapies.

The emerging safety profile of JAK inhibitors in rheumatic disease

Background Necroscopic and surgical studies have suggested that giant cell arteritis (GCA) may target the aorta and its main branches. Imaging techniques are able to detect large vessel vasculitis (LVV) non-invasively in patients, but the prevalence of LVV in GCA has not been clearly established. Objective To assess prospectively the prevalence, characteristics and topography of LVV in patients with newly diagnosed GCA and to determine the associated clinical and laboratory features. Methods CT angiography (CTA) was performed in 40 consecutive patients with newly diagnosed biopsy-proven GCA. Patients were treatment-naive or had been treated with corticosteroids for Results LVV was detected in 27 patients (67.5%). The vessels involved were as follows: aorta (26 patients, 65%), brachiocephalic trunk (19 patients, 47.5%), carotid arteries (14 patients, 35%), subclavian arteries (17 patients, 42.5%), axillary arteries (7 patients, 17.5%), splanchnic arteries (9 patients, 22.5%), renal arteries (3 patients, 7.5%), iliac arteries (6 patients, 15%) and femoral arteries (11 patients, 30%). Dilation of the thoracic aorta was already present in 6 patients (15%). Cranial ischaemic events were significantly less frequent in patients with LVV (p=0.029). Treatment-naive patients had a higher frequency of LVV (77% vs 29%, p=0.005). Conclusions CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

https://ard.bmj.com/content/annrheumdis/71/7/1170.full.pdf

Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography

Among immunocompromised patients with immune mediated inflammatory diseases (IMIDs), those undergoing therapy with B cell depleting agents are among the most vulnerable to both severe COVID-19 disease and sub-optimal response to COVID-19 vaccines(1). Numerous studies have documented suppressed humoral, but relatively maintained cell mediated, responses to COVID-19 vaccines in these patients. However, the clinical significance of such immunity in terms of protection from infection and its sequelae are poorly understood. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes.To define the frequency and outcomes of COVID-19 breakthrough infection in fully or partially vaccinated IMIDs patients receiving B cell depleting therapies.To assess the characteristics and risk factors for severe outcomes and death.All pharmacy records from within a large health care system were electronically searched for patients undergoing B cell depleting therapies with approved monoclonal antibodies in 2020. Records with ICD codes for IMIDs but not malignancies were included; patients must also have had at least one documented COVID-19 vaccine. From this cohort all patients with breakthrough COVID-19 disease from time of 1st vaccination through December 15, 2021 were identified; each record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, use of monoclonal antibodies, dose and timing of B cell depleting therapy, and outcomes as assessed by an 8 point NIH ordinal scale. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes.A total of 1677 IMIDs patients were identified who received any B cell depleting monoclonal antibody and at least one COVID-19 vaccine in 2021. From this cohort 74 patients (4.4%) experienced a breakthrough COVID-19 infection. Among the breakthrough patients 34 (46%) had a rheumatic disease (RA 11, AAV 15, SLE 2), 34 (46%) had CNS inflammatory disease (MS 32, 2 other), and 6 (8%) had immune hematologic/miscellaneous diseases. Four patients had a previous history of COVID-19 infection. Overall 24 (35%) were hospitalized with 11 patients requiring critical level care (15%) and 6 deaths (8 %). All fatal cases had rheumatic diseases. Monoclonal antibodies were given as outpatient therapy to 21 patients and among these only 1 patient was hospitalized without requiring O2 and none died. In univariate analysis only number of comorbidities had a significant positive effect (p=.001) on severe outcomes (i.e. groups 1-4 vs. groups 5-8: Table 1) while monoclonal antibody therapy was associated with more favorable outcomes (p=.005 group 1-2 vs.3-8, Table 1). There were no associations between the dose, duration or timing of the B cell therapy, concomitant therapies including glucocorticoids, vaccine status (incomplete, complete, boosted) or date of vaccination with severe outcomes.In IMIDs patients treated with B cell depleting therapies breakthrough infections are common with many experiencing severe outcomes. Concomitant comorbidities were associated with risk of severe disease. Monoclonal antibody therapy was used in only 28% but was associated with enhanced clinical outcomes with only 1 in 21 requiring hospitalization and zero mortality. This population of immunocompromised patients remains vulnerable to COVID-19 disease despite vaccination. More aggressive use of outpatient management with monoclonal antibody therapy and other preventive and therapeutic measures are urgently needed.[1]Samuel Bitoun et al Rituximab impairs B-cell response but not T-cell response to COVID-19 vaccine in auto-immune diseases First published: 28 December 2021 Arthritis and Rheumatology https://doi.org/10.1002/art.42058cassandra calabrese Speakers bureau: Sanofi-regeneron, Consultant of: Sanofi-regeneron, Elizabeth Kirchner Consultant of: Janssen, M Elaine Husni Consultant of: Abbvie, BMS, Novartis, Lilly, Pfizer, UCB, Regeneron, Janssen, Brandon Moss Consultant of: Biogen advisory board, Grant/research support from: Genentech/Roche and Novartis as part of investigator-initiated studies, Anthony Fernandez Consultant of: Consulting: AbbVie, Novartis, Mallinckrodt, UCB, BMS, Boehringer Ingelheim, Alexion, Grant/research support from: Research: AbbVie, Novartis, Pfizer, Corbus, Mallinckrodt, Yuxuan Jin: None declared, Leonard Calabrese Speakers bureau: Sanofi, Janssen, AbbVie, ChemoCentryx, GSK, AstraZeneca, Consultant of: Sanofi, Jansen, AbbVie, ChemoCentryx, GSK, AstraZeneca, BMS, Genentech

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Pos0194 morbidity and mortality of breakthrough covid-19 in patients with immune mediated conditions on b cell depleting therapies and the effects of monoclonal antibody treatment

Upadacitinib (UPA) is an oral JAK inhibitor that has demonstrated safety and efficacy in patients (pts) with moderate-to-severe active RA in the phase 3 SELECT clinical program.[1–6]To describe the long-term integrated safety profile of UPA relative to active comparators in pts with RA from the SELECT clinical program through the cutoff date of 15 August 2022.Pooled safety data were analyzed from 6 randomized controlled trials evaluating UPA in RA.[1–6]Treatment-emergent adverse events (TEAEs) and AEs of special interest were summarized for the following groups: pooled UPA 15 mg once daily (QD; UPA15, 6 trials), MTX (1 trial), and adalimumab (ADA) 40 mg every other week (EOW; 1 trial). TEAEs were defined as AEs with an onset after the first dose and ≤ 30 days (UPA and MTX) or ≤ 70 days (ADA) after the last dose of study drug and reported as exposure-adjusted event rates (EAERs) per 100 patient-years (PY; E/100 PY). The standardized mortality ratio (SMR) was estimated for the general population using World Health Organization country-age-gender specific mortality rates through 2016.3209 pts received ≥ 1 dose of UPA15 with 10 782.7 PY of exposure. EAERs of AEs, serious AEs (SAEs), and AEs leading to discontinuation on UPA15 were comparable to MTX and ADA (Table 1). COVID-19 pneumonia was the most common SAE with UPA15 (0.7 E/100 PY). Rates of serious infections were similar between UPA15 and ADA but higher compared with MTX (Figure 1). Herpes zoster (HZ) rates were higher with UPA15 vs MTX and ADA. Most HZ cases with UPA15 were non-serious (95%) and affected a single dermatome (75%) or unilateral multiple dermatomes (16%); 8% of cases were reported as disseminated and none involved the central nervous system. Creatine phosphokinase elevations were transient and more common with UPA15 than MTX or ADA. Anemia and neutropenia rates were similar between UPA15 and ADA. Most hepatic disorders were mild or moderate transaminase elevations. Treatment discontinuation due to these lab events was rare (≤ 0.1 E/100 PY). Similar rates of adjudicated MACE, adjudicated VTE, and malignancy (excluding non-melanoma skin cancer [NMSC]) were observed across treatment groups. The rate of NMSC was numerically higher with UPA15 vs ADA; no cases occurred with MTX. SMR analysis indicated that the mortality rate among pts with RA treated with UPA15 was not higher than what would be expected among the general population (SMR [95% CI]: 0.67 [0.52, 0.86] including COVID-19 deaths; 0.41 [0.29, 0.56] excluding COVID-19 deaths).The integrated safety profile of UPA in pts with RA remained consistent with previous findings,[7]with no new safety risks identified up to 6.5 years of exposure. Similar rates of AEs of special interest were observed for UPA15 and ADA, except for higher rates of HZ, CPK elevations, and NMSC with UPA.[1]Burmester GR, et al.Lancet. 2018;391:2503–12.[2]Smolen JS, et al.Lancet. 2019;393:2303–11.[3]Fleischmann R, et al.Arthritis Rheumatol. 2019;71:1788–1800.[4]Genovese MC, et al.Lancet. 2018;391:2513–24.[5]van Vollenhoven R, et al.Arthritis Rheumatol. 2020;72:1607–20.[6]Rubbert-Roth A, et al.N Engl J Med. 2020;383:1511–21.[7]Cohen SB, et al.Ann Rheum Dis2020;79:319–20.Table 1.Treatment-emergent Adverse Events in Patients Treated with UPA, ADA, and MTXUPA 15 mg QDADA 40 mg EOWMTXn (number of subjects)3209579314ExposureTotal PY10 782.71573.2865.1Mean (SD), years3.4 (1.9)2.7 (2.3)2.8 (2.0)Median (range), years4.0 (0.0, 6.6)2.2 (0.0, 6.6)2.6 (0.0, 5.4)E/100 PY (95% CI)Any AE206.1(203.4, 208.8)195.5(188.6, 202.5)203.2(193.8, 212.9)Any SAE12.8(12.2, 13.5)13.5(11.7, 15.4)9.0(7.1, 11.3)Any AE leading to study drug discontinuation4.8(4.4, 5.2)5.5(4.4, 6.8)5.5(4.1, 7.4)Any COVID-19-related AE4.6(4.2, 5.0)4.7(3.7, 5.9)2.4(1.5, 3.7)Deathsa0.8(0.7, 1.0)1.0(0.5, 1.6)0.9(0.4, 1.8)ADA, adalimumab; E/100 PY, exposure-adjusted event rates per 100 patient-years; QD, once daily; SAE, serious AE; UPA, upadacitinib.aIncludes treatment-emergent, non-treatment-emergent, and COVID-related deaths.AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Stanley B. Cohen Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz, Ronald van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Jeffrey Curtis Consultant of: AbbVie, Amgen, BMS, CorEvitas, Eli Lilly, Janssen, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, BMS, CorEvitas, Eli Lilly, Janssen, Pfizer, Sanofi, and UCB, Leonard Calabrese Speakers bureau: AbbVie, BMS, Crescendo, Genentech, Gilead, GSK, Horizon, Janssen, Novartis, and Sanofi, Consultant of: AbbVie, BMS, Crescendo, Genentech, Gilead, GSK, Horizon, Janssen, Novartis, and Sanofi, Cristiano Zerbini Speakers bureau: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Consultant of: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Grant/research support from: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Consultant of: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Grant/research support from: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Louis Bessette Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Christophe Richez Speakers bureau: Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, Galapagos, GSK, Hospira, Mylan, Novartis, Pfizer, Roche, and Sandoz, Consultant of: Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, Galapagos, GSK, Hospira, Mylan, Novartis, Pfizer, Roche, and Sandoz, sander strengholt Shareholder of: AbbVie, Employee of: AbbVie, Derek Coombs Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Andrew Gara Shareholder of: AbbVie, Employee of: AbbVie, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB.

/pdf/pos0826-safety-profile-of-upadacitinib-up-to-6-5-years-of-1ghgy7eh.pdf

Pos0826 safety profile of upadacitinib up to 6.5 years of exposure in patients with rheumatoid arthritis

http://www.jidonline.org/article/S0022202X23001859/pdf

L. Calabrese

Papers

Pos0194 morbidity and mortality of breakthrough covid-19 in patients with immune mediated conditions on b cell depleting therapies and the effects of monoclonal antibody treatment

Pos0826 safety profile of upadacitinib up to 6.5 years of exposure in patients with rheumatoid arthritis

009 The transcriptome of Sweet syndrome suggests a pathogenic role of both innate and adaptive immune signaling pathways