Incidence of Antidrug Antibodies in Rheumatoid Arthritis Patients From Argentina Treated With Adalimumab, Etanercept, or Infliximab in a Real-World Setting

Maid, Pablo; Xavier, Ricardo Machado; Real, Rosa M.; Pedersen, Ron; Shen, Qi; Marshall, L.; Solano, Gastón; Borlenghi, Cecilia; Hidalgo, Rodolfo Pardo

doi:10.1097/rhu.0000000000000612

Cited by 10 publications

(15 citation statements)

References 18 publications

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“…Concerns have been raised over the therapeutic implications of the development of neutralizing antidrug antibodies to bDMARDs [15,16], which may be the underlying rationale for recommending continuation with methotrexate monotherapy once good disease control has been achieved on combination therapy. The development of neutralizing antidrug antibodies to TNFis other than etanercept have been reported [15,16,[30][31][32][33][34], and may be one factor contributing to the different persistence rates detected in our study. Similarly, the higher discontinuation rates reported for other TNFis than for etanercept in long-term registry studies [35,36] is consistent with our findings.…”

Section: Discussionmentioning

confidence: 63%

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data

Pappas

Litman²,

Lesperance³

et al. 2020

Rheumatol Int

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Biological disease-modifying antirheumatic drugs (bDMARDs) monotherapy may enhance adherence and decrease adverse events compared to combination therapy with conventional synthetic DMARDs (csDMARDs); however, persistence with bDMARD monotherapy has not been extensively studied. We explore persistence of etanercept monotherapy and monotherapy with other tumor necrosis factor inhibitors (TNFis) among patients first achieving remission/low disease activity (LDA) while on combination therapy with csDMARDs and a TNFi. Using Corrona registry data, the percentage of patients persistent with the index TNFi (etanercept versus other TNFis) over 6 and 12 months was determined. Factors influencing persistence and treatment patterns at 6 and 12 months were examined. Among 617 eligible patients, 56% of 182 patients on etanercept and 45% of 435 patients on other TNFis persisted with monotherapy at 6 months, 46% and 33%, respectively, at 12 months. Across first-line and subsequent biologic DMARDs, etanercept persistence was greater than other TNFi persistence by 10.8% (95% CI 2.1%, 19.6%) at 6 months and 11.4% (95% CI 0.9%, 21.9%) at 12 months. Patients on other TNFis were more likely to require reintroduction of csDMARD after 6 months (45% versus 35% for etanercept). Remission was the key predictor of persistence for both etanercept and other TNFi monotherapies. This retrospective, cohort study of registry data reflecting real-world practice indicates patients who achieve remission/LDA with combination csDMARD and TNFi therapy may successfully transition to TNFi monotherapy. Patients on etanercept monotherapy experienced greater persistence and less frequent reintroduction of a csDMARD than was observed for patients on other TNFi monotherapies.

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Section: Discussionmentioning

confidence: 63%

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data

Pappas

Litman²,

Lesperance³

et al. 2020

Rheumatol Int

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“…There are several clinical studies comparing treatment efficacy and side-effects between infliximab, adalimumab, and etanercept [239][240][241][242]. Here, it was shown that TNF-α neutralizing antibodies possess a high potential to induce the production of anti-drug antibodies (ADAs) (detection of ADAs within 18 months of treatment in either the adalimumab (19.2%-31.2% of patients) or infliximab group (17.4-29.4% of patients)) [239][240][241]243]. ADAs can not only decrease drug levels in serum, but also raise safety concerns like induction of type I-III hypersensitivity responses [244].…”

Section: Tnf-α Inhibitorsmentioning

confidence: 99%

“…The lack of the human Fc domain in certolizumab pegol reduces the possibility for ADA generation. Consequently, clinical results demonstrated that none or only low levels of ADAs were detected in certolizumab pegol-treated patients [241], while several studies indicated a high immunogenicity of both infliximab and adalimumab which might lead to the development of ADAs [239][240][241]243]. The induction of ADAs against adalimumab and infliximab is associated with both major and minor clinical adverse effects [243].…”

Section: Tnf-α Inhibitorsmentioning

confidence: 99%

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Lin

Anzaghe

Schülke

2020

Cells

582

376

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Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

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“…For example, the presence of IL‐6 and IL‐1 β in parallel with TNF‐α may lead to inhibition of erythropoiesis, which, unlike the myeloid lineage, leads to a decrease in erythrocyte counts (Pierce & Larson, 2005). Inhibition of TNF‐α using TNF‐α signaling inhibitors such as infliximab, etanercept, adalimumab, and golimumab could be an effective approach to reverse erythropoiesis and increase erythroid precursors in BM diseases as well as preventing inflammation in inflammatory diseases (Table 2; Brenner et al, 2015; Maid et al, 2018). Thus, although the presence of TNF‐α may play a role in stimulating hematopoiesis (induction of megakaryopoiesis and myeloid differentiation), TNF‐α inhibition could also lead to the recovery of erythropoiesis and prevent the progression of inflammation.…”

Section: Tumor Necrosis Factor‐αmentioning

confidence: 99%

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate

Najafi

Ghanavat

Shahrabi

et al. 2021

Cell Biology International

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Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English‐language articles (1995–2020) using “Hematopoietic stem cell,” “Inflammatory cytokine,” “Homeostasis,” and “Myelopoiesis.” Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.

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Incidence of Antidrug Antibodies in Rheumatoid Arthritis Patients From Argentina Treated With Adalimumab, Etanercept, or Infliximab in a Real-World Setting

Abstract: In this subset analysis, RA patients from Argentina treated with adalimumab or infliximab, but not etanercept, tested positive for ADAs. Antidrug antibody-negative patients showed a tendency toward better clinical outcomes compared with ADA-positive patients.

Cited by 10 publications

References 18 publications

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate

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