A multi-parameter response prediction model for rituximab in rheumatoid arthritis

Jong, Tamarah D. de; Sellam, Jérémie; Agca, Rabia; Vosslamber, Saskia; Witte, Birgit I.; Tsang-A-Sjoe, M.; Mantel, Elise; Bijlsma, J. W. J.; Voskuyl, Alexandre E.; Nurmohamed, Michael T.; Verweij, Cornelis L.; Mariette, Xavier

doi:10.1016/j.jbspin.2017.02.015

Cited by 15 publications

(11 citation statements)

References 38 publications

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“…Overall, it is feasible that the distinct profiles of the IFN response observed may be a source of controversy in relation to previous studies. Although some confounders, which can alter the IFN response have been reported ( 14 , 25 , 29 , 30 ), they were restricted to the degree of activation. However, this is the first time that a qualitative insight is addressed.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limitation for Its Use As a Clinical Biomarker

et al. 2018

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IntroductionAn increased expression of interferon (IFN)-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA). However, some controversy exists concerning its clinical relevance. The main aim of this study is to evaluate whether quantitative and qualitative differences in the activation of the IFN pathway may account for these findings.MethodsThe expression of IFN-induced protein 44 (IFI44), IFN-induced protein 44 like (IFI44L), IFN alpha inducible protein 6, and MX dynamin-like GTPase 1 (MX1) was determined in peripheral blood in 98 RA patients (IFI6) and 28 controls. RA patients were classified into groups according to their clinical stage and treatments received: very early RA (VERA), biological disease-modifying antirheumatic drug (bDMARD) naive, and bDMARD. An additional group of 13 RA patients candidates for tumor necrosis factor alpha (TNFα) blockade was also recruited. The associations among IRGs were evaluated by network and principal component analyses.ResultsThe expression of all IRGs was increased in RA to different levels. The IFN score was increased in all RA groups (VERA, bDMARD-naïve, and bDMARD), but important differences in their degree of activation and in the relationships among IRGs were observed. The IFN score correlated with the accumulated disease activity score 28-joints, and it was found to be a predictor of clinical outcome in VERA. No differences in the IFN score were observed between the bDMARD-naive and bDMARD groups, but opposite associations with the clinical parameters were noted. Interestingly, the correlations among IRGs delineate different pictures between these two groups. The IFN score at baseline predicted poor clinical outcome upon TNFα blockade. Although no absolute changes in the IFN score were found, TNFα-blockade shifted the associations among IRGs.ConclusionA certain heterogeneity within the IFN signature can be recognized in RA, depending on the clinical stage. The structure of the IFN signature may be a potential explanation for the controversy in this field and must be considered to decipher its clinical relevancein RA.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limitation for Its Use As a Clinical Biomarker

et al. 2018

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“…A persistent upregulation of IRG, the type I IFN signature, is evident in several autoimmune diseases including systemic lupus erythematosus (SLE) and RA [9]. In RA, the expression of IRG is upregulated in peripheral blood compared to controls [10] and was suggested to associate with disease activity [11] and predict treatment response to tumor necrosis factor inhibitors (TNFi) [12][13][14], interleukin-6 receptor inhibitors (IL-6Ri) [15], and B-cell depletion therapy [16][17][18][19]. However, the stimulation of IRG expression is not specific for IFNα and which genes to include is not standardized.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Anti-tumor necrosis factor (TNF) α antibody therapies, if effective for RA, can cause fatal hemophilia in some cases [ 40 , 41 ]. The first-choice treatment in our case was rituximab (anti-B cells therapy), as its efficacy and safety in acquired hemophilia and RA are widely demonstrated [ 42 – 47 ]. Indeed, the aim of the treatment was to target the B lymphocyte secreting the anti-FVIII inhibitor, the rheumatoid factor, and the anti-CCP [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting Acquired Hemophilia A with Rheumatoid Arthritis by a Rituximab Shot: A Case Report and Review of the Literature

et al. 2018

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Patient: Male, 66Final Diagnosis: Acquired hemophilia ASymptoms: Polyarticular flareMedication: —Clinical Procedure: —Specialty: RheumatologyObjective:Challenging differential diagnosisBackground:Acquired hemophilia A (AH) is a rare hemorrhagic diathesis, characterized by the presence of autoantibodies directed against the pro-coagulant activity of factor VIII. It is associated with rheumatoid arthritis (RA) in 4% to 8% of cases and its prognosis remains severe.Case Report:A 66-year-old patient has been followed up for 20 years for deforming and severe RA, which was in low-disease activity. However, the patient presented a polyarticular flare involving the metacarpophalangeal and the proximal interphalangeal joints, the left elbow, and the right knee, which was warm and swollen. Articular puncture of this knee yielded a hematic fluid that did not coagulate. Its cytological analysis showed significant presence of red blood cells, which were also abundantly present in the other cell lines. Activated partial thromboplastin time was lengthened and not corrected by the addition of control plasma. Prothrombin time (Quick’s test), fibrinogen level, and vitamin K-dependent factors were without abnormalities. In contrast, factor VIII was collapsed at 7% and the anti-factor VIII antibody was positive. The diagnosis of AH with anti-factor VIII inhibitor was thus retained. With regard to RA, the Disease Activity Score was 6.32 and exhibited a very active RA. Rituximab with methotrexate was begun and the evolution was favorable. After 6 months, the reappearance of the anti-factor VIII inhibitor was found, thus justifying a second cycle of rituximab.Conclusions:AH is not exceptional in RA. Rituximab remains a relevant alternative for managing simultaneous AH with inhibitor and RA.

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A multi-parameter response prediction model for rituximab in rheumatoid arthritis

Cited by 15 publications

References 38 publications

Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limitation for Its Use As a Clinical Biomarker

Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limitation for Its Use As a Clinical Biomarker

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

Targeting Acquired Hemophilia A with Rheumatoid Arthritis by a Rituximab Shot: A Case Report and Review of the Literature

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