scholarly journals Monitoring Drug and Antidrug Levels: A Rational Approach in Rheumatoid Arthritis Patients Treated with Biologic Agents Who Experience Inadequate Response While Being on a Stable Biologic Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Diana Mazilu ◽  
Daniela Opriş ◽  
Cecilia Gainaru ◽  
Mihaela Iliuta ◽  
Natalia Apetrei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Drug Level ◽  
Biologic Agents ◽  
Rational Approach ◽  
Inadequate Response ◽  
Das28 Score ◽  
Eular Response ◽  
Biologic Treatment ◽  
Serum Drug Level

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P=0.038) with lower DAS28 and SDAI scores (P=0.01andP=0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P=0.002andP=0.023), DAS28 score (P=0.002andP=0.003), and SDAI score (P=0.001andP=0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.

scholarly journals SAT0006 SIMULTANEOUS ANALYSIS OF ANTI-CCP, RHEUMATOID FACTOR, ANTI-PAD4 AND ANTI-CARBAMYLATED PROTEIN ANTIBODIES REVEALS INTERACTION EFFECTS WITH RESPONSE TO ANTI-TNF THERAPY IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 933.2-934
Author(s):  
A. Julià ◽  
M. Lopez Lasanta ◽  
F. Blanco ◽  
A. Gómez ◽  
I. Haro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Clinical Response ◽  
Therapeutic Approach ◽  
Drug Response ◽  
Single Marker Analysis ◽  
Das28 Score ◽  
Positive Interaction ◽  
Single Marker ◽  
Necrosis Factor

Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared

scholarly journals OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S026-S027
Author(s):  
S W Schreiber ◽  
M Ferrante ◽  
R Panaccione ◽  
J F Colombel ◽  
T Hisamatsu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Unmet Need ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic Literature Review

2017 ◽  
Vol 44 (6) ◽  
pp. 773-779 ◽  
Author(s):  
Julia Mary ◽  
Michel De Bandt ◽  
Cédric Lukas ◽  
Jacques Morel ◽  
Bernard Combe
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factors ◽  
Disease Activity ◽  
Functional Disability ◽  
Relative Effectiveness ◽  
Response Criteria ◽  
Cochrane Library ◽  
Inadequate Response ◽  
Eular Response ◽  
Necrosis Factor

Objective.For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure.Methods.We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ).Results.Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments.Conclusion.In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.

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