Serum golimumab concentration and anti-drug antibodies are associated with treatment response and drug survival in patients with inflammatory joint diseases: data from the NOR-DMARD study

Abstract Objectives To identify a therapeutic target interval for certolizumab pegol drug levels and examine the influence of anti-drug antibodies in patients with inflammatory joint diseases. Methods Certolizumab pegol and anti-drug antibody levels were measured in serum samples collected after 3 months of certolizumab pegol treatment in 268 patients with inflammatory joint diseases (116 axial spondyloarthritis, 91 rheumatoid arthritis and 61 psoriatic arthritis) in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score Clinically important improvement in axial spondyloarthritis, European League Against Rheumatism good/moderate response in rheumatoid arthritis, and improvement in 28-joint Disease Activity Score of ≥ 0.6 in PsA. Serum drug levels and anti-drug antibodies were analysed using automated in-house assays. Results Certolizumab pegol serum levels varied considerably between individuals (median (IQR) 32.9 (17.3–43.9) mg/L). Certolizumab pegol level ≥ 20 mg/L was associated with treatment response for the total inflammatory joint disease population, with odds ratio (OR) 2.3 (95% CI 1.2–4.5, P = 0.01) and OR 1.9 (95% CI 1.0–3.5, P = 0.05) after 3 and 6 months of treatment, respectively. For individual diagnoses, this association was most consistent for axial spondyloarthritis, with OR 3.4 (95% CI 1.0–11.1, P < 0.05) and OR 3.3 (95% CI 1.0–10.8, P < 0.05), respectively. Certolizumab pegol level > 40 mg/L was not associated with any additional benefit for any of the diagnoses. Anti-drug antibodies were detected in 6.1% (19/310) of samples and were associated with low certolizumab pegol levels (P < 0.01). Conclusions Serum certolizumab pegol levels 20–40 mg/L were associated with treatment response in inflammatory joint diseases. Our study is the first to show this association in axial spondyloarthritis and psoriatic arthritis patients. The results suggest a possible benefit of therapeutic drug monitoring in patients with inflammatory joint disease on certolizumab pegol treatment. Trial registration NCT01581294, April 2012.

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SAT0264 Does biological disease-modifying anti-rheumatic drug naÏve versus non-naÏve patients with inflammatory joint diseases have similar golimumab drug survival and efficacy? data from the prospective observational nor-dmard study

10.1136/annrheumdis-2018-eular.1885 ◽

2018 ◽

Cited By ~ 1

Author(s):

B. Michelsen ◽

J. Sexton ◽

T.K. Kvien

Keyword(s):

Joint Diseases ◽

Efficacy Data ◽

Drug Survival ◽

Inflammatory Joint Diseases ◽

Drug Naïve ◽

Disease Modifying ◽

Rheumatic Drug

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O14 Semi-quantitative assessment of synovial inflammation on US guided synovial membrane biopsy is contingent to disease phase, autoimmune profile and treatment response in RA: a large single center experience

Rheumatology ◽

10.1093/rheumatology/keaa110.013 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Stefano Alivernini ◽

Barbara Tolusso ◽

Marco Gessi ◽

Maria Rita Gigante ◽

Luca Petricca ◽

...

Keyword(s):

Treatment Response ◽

Quantitative Assessment ◽

Clinical Care ◽

Power Doppler ◽

Doppler Signal ◽

Sustained Remission ◽

Joint Diseases ◽

Single Center ◽

Inflammatory Joint Diseases ◽

Power Doppler Signal

Abstract Background Ultrasound (US)-guided minimally-invasive synovial tissue (ST) biopsy is a well-tolerated procedure for basic and translational studies on chronic inflammatory joint diseases as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). The aim of the study was to evaluate the utility of histopathologic criteria to differentiate US-guided ST biopsies in daily clinical care in relation to diagnosis, disease characteristics, US parameters and treatment response in a large single center ST biopsy unit. Methods 1,064 patients [545 RA, 167 PsA, 75 SpA, 199 undifferentiated peripheral inflammatory arthritis (UPIA), 18 crystal arthritis, 26 connective tissue diseases and 34 osteoarthritis (OA) respectively] who underwent US-guided ST biopsy were enrolled. US parameters (Synovial Hyperthrophy and Power Doppler signal respectively) were recorded for each biopsied joint. RA, PsA and SpA patients were stratified based on disease activity phase (naive to DMARDs, DMARDs resistant and in sustained remission, respectively). Clinical, demographic and immunological characteristics were recorded for each patient. All ST FFPE specimens were routinely processed and stained with H&E and classified by a pathologist, blinded to clinical characteristics, using the Krenn score to assess the degree of ST inflammation. Moreover, the presence/absence of lymphocytes, plasmacells, granulocytes and oedema was assessed for each ST. All naive to treatment RA were treated according to the T2T scheme and followed for at least 12 months and DAS remission rate was recorded. Results In the cohort, the distribution of synovitis score was significantly different among patients with inflammatory chronic diseases (RA, PsA, SpA and UPIA respectively) compared to OA (ANOVA Test p < 0.001). Moreover, Krenn score directly correlated with synovial hyperthrophy (R = 0.36; p < 0.001) and Power Doppler signal (R = 0.40;p<0.001) of the biopsied joint. Considering the RA cohort, naive RA showed a higher Krenn score compared to resistant RA (p < 0.001) and RA in sustained clinical and US remission (p < 0.001), directly correlating with DAS28 (R = 0.51; p < 0.001). Moreover, ACPA and RF positivity was related to the Krenn score and to ST plasmacells presence at RA onset (p < 0.05 and p < 0.001, respectively) but not at the time of DMARDs-failure or sustained remission achievement (p > 0.05 for both). Stratifying naive RA based on disease duration at ST biopsy, naive RA with symptoms duration >1 year, showed higher Krenn score compared to those with symptoms duration <3 months (p < 0.001). Finally, logistic regression analysis revealed that Krenn score higher or equal to 4.5 at baseline is an independent factor of no DAS remission achievement within 12 months [OR(95%CI):0.37(0.20-0.67)p<0.001] in naive RA. Conclusion Krenn score is a reliable tool for the semi-quantitative assessment of ST inflammation on US-guided ST biopsies being differentially distributed among various chronic inflammatory joint diseases and contingent to disease phase, autoimmune profile and therapeutic response in RA. Disclosures S. Alivernini None. B. Tolusso None. M. Gessi None. M. Gigante None. L. Petricca None. C. Di Mario None. S. Perniola None. A. Fedele None. G. Peluso None. L. Bui None. A. Capacci None. F. Federico None. G. Ferraccioli None. E. Gremese None.

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Quantification of perfusion and endothelial permeability in inflammatory joint diseases

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren ◽

10.1055/s-0028-1124044 ◽

2009 ◽

Vol 181 (01) ◽

Author(s):

S Weckbach ◽

SP Sourbron ◽

M Notohamiprodjo ◽

H Hatz ◽

MF Reiser ◽

...

Keyword(s):

Endothelial Permeability ◽

Joint Diseases ◽

Inflammatory Joint Diseases

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Mechanisms and Mediators of Pain in Chronic Inflammatory Arthritis

Current Treatment Options in Rheumatology ◽

10.1007/s40674-021-00178-x ◽

2021 ◽

Author(s):

Marco Di Carlo ◽

Gianluca Smerilli ◽

Fausto Salaffi

Keyword(s):

Inflammatory Pain ◽

Inflammatory Arthritis ◽

Operational Definition ◽

Immunosuppressive Drugs ◽

Therapeutic Strategies ◽

Future Research ◽

Common Symptom ◽

Joint Diseases ◽

Chronic Inflammatory Arthritis ◽

Inflammatory Joint Diseases

Abstract Purpose of the review Pain in chronic inflammatory joint diseases is a common symptom reported by patients. Pain becomes of absolute clinical relevance especially when it becomes chronic, i.e., when it persists beyond normal healing times. As an operational definition, pain is defined chronic when it lasts for more than 3 months. This article aims to provide a review of the main mechanisms underlying pain in patients with chronic inflammatory joint diseases, discussing in particular their overlap. Recent findings While it may be intuitive how synovial inflammation or enthesitis are responsible for nociceptive pain, in clinical practice, it is common to find patients who continue to complain of symptoms despite optimal control of inflammation. In this kind of patients at the genesis of pain, there may be neuropathic or nociplastic mechanisms. Summary In the context of chronic inflammatory joint diseases, multiple mechanisms generally coexist behind chronic pain. It is the rheumatologist’s task to identify the mechanisms of pain that go beyond the nociceptive mechanisms, to adopt appropriate therapeutic strategies, including avoiding overtreatment of patients with immunosuppressive drugs. In this sense, future research will have to be oriented to search for biomarkers of non-inflammatory pain in patients with chronic inflammatory joint diseases.

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THU0378 DO COMORBIDITIES DECREASE THE FIRST TNF-INHIBITOR RETENTION AND TREATMENT RESPONSE IN AXIAL SPONDYLOARTHRITIS PATIENTS? DATA FROM TURKBIO

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2925 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 422-423

Author(s):

Y. Erez ◽

A. Karakas ◽

S. B. Kocaer ◽

T. Yüce İnel ◽

S. Gulle ◽

...

Keyword(s):

Disease Activity ◽

Treatment Response ◽

Axial Spondyloarthritis ◽

Cerebrovascular Event ◽

Tnf Inhibitor ◽

Drug Survival ◽

Drug Retention ◽

Significant Difference ◽

Baseline Characteristics ◽

The Impact

Background:The frequency of comorbidities has increased in spondyloarthritis patients compared to the general population. The effect of comorbidities on tumour necrosis factor alpha inhibitor (TNFi) drug retention and treatment response has not been well evaluated.Objectives:The purpose of this study to assess the impact of comorbidities on the first TNFi drug survival and treatment response in patients with axial spondyloarthritis (axSpA) registered in theTURKBIOdatabase.Methods:In this study, the frequency of comorbidities, disease activity scores at baseline and month 6 and drug retention were recorded in AxSpA patients iniating first TNFi treatment between 2011 and 2019. Kaplan Meier plot and log rank tests were used for drug survival analysis. Cox regression analysis with HR was performed to evaluate the correlation between comorbidities and drug survival.Results:There were 2428 patients with AxSpA (39.3% female) who used their first TNFi during the study period. Among them, a total of 770 (31%) had at least one comorbid disease. Hypertension was the most common comorbidity (9.7%), followed by the affective disorders (8%) and chronic lung disease (5.8%). The baseline characteristics of patients are shown in Table 1.The presence of any comorbidity did not impact the first TNFi retention (Figure 1). When comorbidities were analysed seperately, we found that only history of cerebrovascular event was negatively associated with drug retention rate (HR: 6.9, p:0.008). There was no statistically significant difference in Bath AS Disease Activity Index 50% (BASDAI50) response between patients with and without comorbidity at 6 months. Less axSpA patients with comorbidity achieved a ASDAS score ≤ 2.1 compared to patients without comorbidity at 6 months.Table 1.Baseline Characteristics of PatientsRadiographic Spondyloarthritis, n (%)2318 (95.5)Female, n(%)954 (39.3)Age, year42.2±11.8Age at diagnosis, years32.5± 11.3Age at initial TNFi, years39.4 ± 11.1Symptom duration, years9.7± 7.5Time to initial TNFi, years7±6.8HLA-B27- positivity, n (%)1144 (47.1)Smokers, n (%)1068 (44)Baseline BASDAI35.5±22.2Baseline ASDAS-CRP2.8±1.1Baseline CRP (mg/L)15.7±24.4VAS global patient46.6±28.7-Quantitative variables are presented as mean ± SD, and qualitative variables are presented as frequency and percentage-ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein VAS, visual analogue scaleConclusion:The results of this study demonstrated that the presence of previous cerebrovascular event decreased the first TNFi survival in patients with axSpA. It also suggested that comorbidities might decrease TNFi treatment response.Disclosure of Interests:None declared

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Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

Biomedicines ◽

10.3390/biomedicines9080902 ◽

2021 ◽

Vol 9 (8) ◽

pp. 902

Author(s):

Susanne N. Wijesinghe ◽

Mark A. Lindsay ◽

Simon W. Jones

Keyword(s):

Rheumatoid Arthritis ◽

Articular Cartilage ◽

Joint Diseases ◽

Synovial Joint ◽

Pharmacological Treatments ◽

In Vivo Models ◽

Inflammatory Joint Diseases ◽

Joint Pathology ◽

Cellular Pathways

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

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