Sustained complete remission of metastatic melanoma on targeted therapy and rituximab for rheumatoid arthritis

2019 ◽  
Vol 17 (6) ◽  
pp. 638-639
Author(s):  
Robin Reschke ◽  
Johannes Kohlmann ◽  
Christoph Baerwald ◽  
Mirjana Ziemer
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
Complete Remission ◽  
Metastatic Melanoma

scholarly journals AB0235 RITUXIMAB (BIOSIMILAR) IN RHEUMATOID ARTHRITIS: CLINICAL & IMMUNOLOGICAL RESPONSE TO VARYING DOSES- EXPERIENCES FROM A TERTIARY CARE CENTER IN SOUTH INDIA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1143.2-1144
Author(s):  
J. Antony ◽  
R. Sankaralingam ◽  
R. Maheshwari ◽  
B. Chilukuri ◽  
S. Chinnadurai
Keyword(s):  
Rheumatoid Arthritis ◽  
Computed Tomography ◽  
Interstitial Lung Disease ◽  
Complete Remission ◽  
Lung Disease ◽  
Clinical Remission ◽  
Clinical Indication ◽  
Fixed Dose ◽  
Double Negative ◽  
Lung Involvement

Background:Rituximab (RTX) is a chimeric monoclonal antibody against CD20. There is a paucity of studies done with RTX biosimilars. This is a Retrospective and Observational study from January 2018 to December 2019 done in the Department of Clinical Immunology & Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.Objectives:1.To find the effects of varying doses of RTX in attaining clinical remission in RA.2.To find if CD19, CD20 & IgG help in identifying impending flare & if these levels help in deciding the timing of the next dose of RTX.Methods:Rheumatoid arthritis (RA) cases who were given Rituximab from January 2018 were selected. Clinical Response at 6 & 12 months & wherever feasible at 18 & 24 months was assessed by Simplified Disease Activity index (SDAI). RTX initial dose was given at 0 and 14 days followed by fixed dose at six months interval.CD19, CD20 B cell count, IgG levels were tested in patients in whom it was feasible at baseline & 6 months (select patients at 12,18 &24 months). Patients were divided in to 5 groups (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and (500mg & 1g). Patients were divided into three clinical groups, (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and two treatment groups (500mg & 1g) based on clinical indication for RTX and dose of RTX, respectively. In patients with ILD, CT scan & FVC were compared at baseline & 12 months.Results:29 patients (seropositive 28 (RF/Anti CCP/BOTH+VE), seronegative 1) were given RTX for RA over a 2-year period of which 12 had CD19, CD20 & IgG tested. Mean SDAI reduction from baseline to 6 months post treatment was 30%, 32% & 14% while complete remission (SDAI<3.3) was attained in 100%, 18% & 20% in DMARD naïve, DMARD resistant & ILD groups, respectively. CD19, CD20 & IgG reduced from 18.6%, 18.4% & 18.53g/L to 3.7%,3.7% & 9.7g/L respectively FVC improved from 62.4% to 67% at 12. The percentage of patients with lung involvement >20% reduced from 53.3% to 46.7%. Flare was observed in one patient who received 500mg RTX. CD19, CD20 & IgG levels increased from 7.9%, 8% & 9.8g/L to 27%, 25% & 13g/L respectively. 3 patients in the 1g group were followed up at 12,18 & 24 months. In these patients there were no flares or worsening symptoms. 1 patient was double negative for RF & Anti CCP and this patient did not attain clinical remission even after 2 doses of 1g RTX.Conclusion:[1]Patients with early arthritis (diagnosis made within 1 year) and who were DMARD naïve had an excellent response to Rituximab.[2]Complete remission was observed in more patients the 1g compared to 500mg group.[3]Reduction in CD19 & CD20 was associated with significant reduction in the SDAI score.[4]There was no significant reduction of CD19 & CD20 with 500mg dose of Rituximab where either a partial remission or mild flare was observed.[5]There was reduction in the lung involvement to less than 20%(CT) in few patients with 1g dose.[6]Double negative Rheumatoid arthritis poorly responded to Rituximab.[7]The positive effects of 1g Rituximab could be noted up to 24 months.[8]Flare of RA was associated with significant increase in CD19 & CD20.Disclosure of Interests:None declared

scholarly journals AB0138 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER STRATIFIES SEROPOSITIVE RHEUMATOID ARTHRITIS PATIENTS BASED ON THEIR LIKELIHOOD OF INADEQUATE RESPONSE TO TNF INHIBITOR THERAPIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1096.3-1097
Author(s):  
S. Cohen ◽  
V. Strand ◽  
E. Connolly-Strong ◽  
J. Withers ◽  
L. Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Molecular Signature ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Odds Ratios ◽  
Selection For ◽  
Necrosis Factor

Background:There is an urgent need for precision medicine in targeted therapy selection for the treatment of rheumatoid arthritis (RA). TNF inhibitor (TNFi) therapies are the most prescribed targeted therapy for RA patients, yet the majority of patients fail to achieve a clinically meaningful response using this medication class. A blood-based molecular signature test evaluates RNA and clinical metrics to stratify RA patients based on their likelihood of having an inadequate response to TNFi therapies.1 Patients unlikely to respond to TNFi therapies can be directed to a different treatment option such as a JAK inhibitor, thus reducing the time needed to identify an effective therapy, improving confidence in and adherence to treatment, and increasing the patients’ chance of reaching treat-to-target goals.Objectives:High-titers of anti-cyclic citrillunated protein (anti-CCP) have been independently associated with reduced response to TNFi therapy;2 thus, we evaluated the ability of a blood-based molecular signature response classifier (MSRC) test to stratify RA patients by their likelihood of inadequate response to TNFi therapies – regardless of their positive or negative anti-CCP status.Methods:A subset of patients enrolled in the Network-04 prospective observational trial evaluating the ability of a molecular signature response classifier to stratify patients were subdivided into two groups based upon whether they were positive (N = 72) or negative (N = 74) for anti-CCP. The odds of inadequate response to TNFi therapies were calculated based on whether or not a patient had a molecular signature of non-response to TNFi therapy at baseline before the start of treatment. Odds ratios and confidence intervals were calculated3,4 to represent the strength of association between detecting the molecular signature of non-response and the patient’s failure to achieve ACR50 at 6 months.Results:The odds that a patient with a molecular signature of non-response failed to meet ACR50 criteria at 6 months was approximately three times greater than among those patients who lacked the signal (Table 1). No significant difference in odds ratios was observed between patients who were positive or negative for anti-CCP.Table 1.The odds of patients with a molecular signature of non-response failing to achieve an ACR50 response 6 months after TNF inhibitor therapy initiationOdds ratio (95% confidence interval)Anti-CCP positive3.5 (1.3-9.7)Anti-CCP negative3.1 (1.2-8.3)Conclusion:The MSRC test evaluates RA disease biology and accurately stratifies patients based on their likelihood of having an inadequate response to TNFi therapies, regardless of being negative or positive for anti-CCP autoantibodies. Rheumatologists can use the results of the MSRC test to inform targeted therapy selection for RA patients, instead of their anti-CCP serostatus, eliminating the variability inherent to the anti-CCP measurement and its inability to consistently predict TNFi therapy incompatibility. With the MSRC test, providers can rely on a more predictable and accurate assessment of TNFi therapy success or failure when coordinating patient management.References:[1]Mellors, T. et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine3, 91-104, doi:10.1089/nsm.2020.0007 (2020).[2]Braun-Moscovici, Y. et al. Anti-cyclic citrullinated protein antibodies as a predictor of response to anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis. J Rheumatol33, 497-500 (2006).[3]Szumilas, M. Explaining odds ratios. J Can Acad Child Adolesc Psychiatry19, 227-229 (2010).[4]Sperandei, S. Understanding logistic regression analysis. Biochem Med (Zagreb) 24, 12-18, doi:10.11613/BM.2014.003 (2014).Disclosure of Interests:Stanley Cohen: None declared, Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen,Kiniksa, Lilly,Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

scholarly journals Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy–Mediated Metastatic Melanoma Phenotype

2014 ◽  
Vol 5 (3) ◽  
pp. 264-273 ◽  
Author(s):  
Kim H.T. Paraiso ◽  
Meghna Das Thakur ◽  
Bin Fang ◽  
John M. Koomen ◽  
Inna V. Fedorenko ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma

S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis

2010 ◽  
Vol 31 (7) ◽  
pp. 967-969 ◽  
Author(s):  
Junichi Kikuta ◽  
Kaori Iwai ◽  
Yukihiko Saeki ◽  
Masaru Ishii
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy

Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy

2021 ◽  
Vol 31 (3) ◽  
pp. 272-276
Author(s):  
Jens Tijtgat ◽  
Julia Katharina Schwarze ◽  
Gil Awada ◽  
Bart Neyns ◽  
Sandrine Aspeslagh
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Melanoma Patient ◽  
Braf V600e ◽  
Metastatic Melanoma Patient

B Cell-Targeted Therapy for Rheumatoid Arthritis

Drugs ◽  
2006 ◽  
Vol 66 (5) ◽  
pp. 625-639 ◽  
Author(s):  
R John Looney
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
B Cell

scholarly journals Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma

2019 ◽  
Vol 10 ◽  
Author(s):  
Chune Yu ◽  
Xiaowei Liu ◽  
Jiqiao Yang ◽  
Min Zhang ◽  
Hongyu Jin ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Theory And Practice

scholarly journals Targeted therapy and immunotherapy: Emerging biomarkers in metastatic melanoma

2020 ◽  
Vol 33 (3) ◽  
pp. 390-402 ◽  
Author(s):  
Patricia M. LoRusso ◽  
Kurt Schalper ◽  
Jeffrey Sosman
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma
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