scholarly journals AB0227 SAFETY AND EFFECTIVENESS OF ADALIMUMAB REFERENCE PRODUCT AND BIOSIMILAR IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1139.2-1139
Author(s):  
W. G. Rojas Zuleta ◽  
O. J. Felipe Díaz ◽  
C. Orozco Gonzalez ◽  
J. Barbosa Camacho ◽  
C. L. Giraldo Herrera ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Time ◽  
Reference Product ◽  
Real Life ◽  
Rank Test ◽  
P Value ◽  
Disease Evolution ◽  
Evolution Time ◽  
Log Rank Test

Background:Biological therapy revolutionized the treatment and prognosis of inflammatory arthropathies; however, its high cost has an economic impact on health system and limits its access. Biosimilars are products with similar molecular structure, equivalent efficacy, and comparable safety and immunogenicity, which arise as a necessity to reduce costs. Although, their long-term safety is still to be confirmed1.Objectives:Our aim is to compare the safety and effectiveness between adalimumab reference product and biosimilar in patients with inflammatory arthropathies.Methods:Cohort study of 92 patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in a specialized multicenter health institution in Colombia. Ratio of incidence rates (IR) for Adverse Drug Reactions (ADR) and therapeutic failure (TF) is estimated among patients exposed to reference product and biosimilar. 95% confidence interval (CI) for the ratio is also calculated. ADR and TF Incidences in both groups were calculated using the Kaplan Meier curve.Results:Between October 2019 and October of 2020, 92 patients started adalimumab, 64% (n = 59) reference product and 36% (n = 33) biosimilar (18 naive and 15 switch). 41.3% of patients had a diagnosis of RA, 35% AS and 24% PAs. Additionally, 62% were women, with median age of 53 years (Interquartile Range (IQR): 41-62); disease evolution time of 9 years (IQR: 5-20); and treatment time of 0.8 years (IQR: 0.4-1.04). No statistically significant differences were found according to the drug between diagnosis, evolution time, or disease activity. Of all patients 21 presented ADR; 11 events with reference product (IR 0.18 per 100 person-years), and 10 with biosimilar (IR 0.30 per 100 person-years), IR ratio of 0.61 (95%CI 0.26-1.44; p-value = 0.36). From ADR reactions, 35% were infections, 13% skin disorders and 7.4% hepatobiliary disorders; all were classified as non-serious ADR. 5 TF events were presented, 3 with reference product (IR 0.05 per 100 person-years) and 2 with biosimilar (IR 0.06 per 100 person-years); IR ratio of 0.83 (95% CI 0.09-10.04; p value= 1.00). There was no statistically significant between reference product and biosimilar in time of ADR presentation (Log Rank Test 0.74; p= 0.39) or on TF (Log Rank Test 0.55; p= 0.45).Conclusion:Results shown that analyzed biosimilar is a safe product with a similar rate of ADR and without differences in effectiveness evaluated by TF, although 95% CIs are imprecise. This suggests that use of biosimilars in a real-life setting could be safe and with similar effectiveness, which is correlated with other studies carried out in RA and is an appropriate measure to reduce treatment costs in patients with inflammatory arthropathy.References:[1]Cohen, S. B. et al. Long-term safety, efficacy, and immunogenicity of adalimumab biosimilar BI 695501 and adalimumab reference product in patients with moderately-to-severely active rheumatoid arthritis: results from a phase 3b extension study (VOLTAIRE-RAext). Expert Opin. Biol. Ther.19, 1097–1105 (2019).Acknowledgements:To Medicarte for the supportDisclosure of Interests:Wilmer Gerardo Rojas Zuleta Speakers bureau: Pfizer, Jannsen Cilag, Novartis, Bristol Myers Squibb, Biopass, Amgen, Paid instructor for: Pfizer, Jannsen Cilag, Novartis, Bristol Myers Squibb, Biopass, Amgen, Oscar Jair Felipe Díaz Speakers bureau: Amgen, Jannsen Cilag, Bristol Myers Squibb, Novartis, Ely-Lilly, Catalina Orozco Gonzalez: None declared, Jhyld Barbosa Camacho: None declared, Claudia Lucía Giraldo Herrera Speakers bureau: Jannsen Cilag, Bristol Myers Squib, Amgen, Pfizer, Novartis, Roche, Paid instructor for: Jannsen Cilag, Bristol Myers Squib, Amgen, Pfizer, Novartis, Roche, Jesús G Ballesteros Speakers bureau: Bristol Myers, Pfizar, Amgen, Jannsen Cilag, Paid instructor for: Bristol Myers, Pfizar, Amgen, Jannsen Cilag, Jorge Hernando Donado Gómez: None declared, Natalia Duque Zapata: None declared

scholarly journals AB0317 BIOLOGIC THERAPY OPTIMIZATION IN RHEUMATOID ARTHRITIS PATIENTS IN COLOMBIA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1457.2-1458
Author(s):  
W. G. Rojas Zuleta ◽  
O. J. Felipe Díaz ◽  
A. E. Pantoja Marquez ◽  
R. Giraldo ◽  
J. G. López Velandia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Exposure ◽  
Biologic Therapy ◽  
Standard Dose ◽  
Rank Test ◽  
P Value ◽  
Sustained Remission ◽  
Disease Evolution ◽  
Kaplan Meier

Background:The optimization of biological agents (bDMARD), is a strategy that has proven to be cost effective and its use can reduce the risk related to drug exposure (1–3). It is included in the EULAR management guidelines and in the consensus of the Colombian Rheumatology Association.Objectives:To analyze optimization success of bDMARD therapies in patients with RA.Methods:Cohort study of RA patients in a specialized multicenter institution in Colombia, followed from January 2015 to December 2019. Patients in remission or low activity for at least 6 months with bDMARD, and with at least two consecutive medical visits, were included. Optimization types were dose decrease, application interval increments, or both. Patients who had disease reactivation (DAS28- CPR >3.2) and returned to standard dose, were considered a failure. By Kaplan-Meier analysis, the optimization failure was estimated according to bDMARD typeResults:92 patients were included, 78.26% were women, with a median age of 57 years (IQR 50-64), a disease evolution time of 15 years (IQR 10-21), a treatment of 5.6 years (IQR 2.7-8.0), and optimization of 7.75 months (IQR 3.25-15.75). The most commonly used bDMARD therapies were etanercept 36.96%, tocilizumab 30.43% and adalimumab 16.30%. 69.39% (34) were naive for biological treatment. The 53.26% (49) of patients had a follow-up time greater than 6 months.95.92% remained under optimization scheme without disease activity changes, and 4.08% of patients underwent definitive discontinuation of bDMARD, for sustained therapeutic objective. 8.16% (4) had relapses in the first 6 months after onset, of which 2 patients returned to standard doses. In survival analysis it was observed that patients who were optimized for antiTNF failed faster than the non-antiTNF, although this difference was not statistically significant (Log Rank test 0.003 p value = 0.959). Of the total patients, 28 have been optimized for 12 months or more, of these, 96.43% (27) continue in sustained remission, and 55.56% (15) received combined therapy with s synthetic DMARD (sDMARD).Figure 1.Kaplan MeierConclusion:During follow-up, most patients remain in optimization strategy. In those who continued in sustained remission, more than half received sDMARD, this suggests that their use may be a determining factor in preventing disease relapses. More studies are required to evaluate this hypothesis.References:[1]Niccoli L, Nannini C, Blandizzi C. Personalization of biologic therapy in patients with rheumatoid arthritis: Less frequently accounted choice-driving variables. Ther Clin Risk Manag. 2018;14:2097–111.[2]ASOREUMA. Asociación Colombiana de Reumatología. Consenso sobre recomendaciones para disminución y descontinuación de la terapia biológica en pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica. Rev Colomb Reumatol. 2019 Jan;26(1):11–23.[3]Cantini F, Niccoli L, Nannini C. Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Semin Arthritis Rheum. 2017;47(2):183–92.Disclosure of Interests:None declared

scholarly journals The relationship of the prolonged PR interval with the long-term survival in patients with heart failure undergoing cardiac resynchronization therapy

2020 ◽  
Vol 25 (1) ◽  
pp. 33-38
Author(s):  
A. M. Soldatova ◽  
V. A. Kuznetsov ◽  
T. P. Gizatulina ◽  
L. M. Malishevsky ◽  
S. M. Dyachkov
Keyword(s):  
Cardiac Resynchronization ◽  
Rank Test ◽  
Term Survival ◽  
Log Rank Test ◽  
Group I ◽  
Pr Interval ◽  
Qrs Duration ◽  
Group Ii ◽  
The Relationship

Aim. To assess the relationship between the prolonged PR interval (≥200 ms) and the long-term survival of patients undergoing cardiac resynchronization therapy (CRT).Material and methods. A total of 85 patients (mean age — 55,1Ѓ}9,9 years; men — 81,2%) with NYHA class II-IV heart failure (HF) were examined. The mean follow-up was 34,0Ѓ}21,2 months. Patients with PR<200 ms (n=52) made up group I, with PR≥200 ms (n=33) — group II. Then the patients were divided into subgroups depending on the QRS duration: ≥150 ms (n=33 in group I and n=14 in group II, respectively) <150 ms (n=19 in group I and n=19 in group II, respectively).Results. In patients of group II, a history of myocardial infarction (MI) was more often registered (p=0,005), left ventricular ejection fraction (LVEF) was lower (p=0,032). In a multivariate analysis, MI (OR 3,217; CI 95% 1,188-8,712; p=0,022) and LVEF value (OR 0,869; CI 95% 0,780-0,968; p=0,011) had a significant relationship with the PR interval prolongation (≥200 ms). The survival of patients of group I was 59,6%, group II — 18,2% (Log-rank test p<0,001). According to Cox regression model, the initial left ventricle end-systolic volume (OR 1,012; 95% CI 1,006-1,017; p<0,001), inferior wall MI (OR 1,690; 95% CI 1,131-2,527; p=0,011) and PR interval ≥200 ms (OR 2,179; 95% CI 1,213–3,915; p=0,009) were associated with long-term mortality. In patients with PR≥200 ms, survival rate was low, regardless of the QRS duration (21,4% in patients with QRS≥150 ms, 15,8% in patients with QRS<150 ms; Log-rank test p=0,698) In patients with PR<200 ms, the survival rate of patients with QRS≥150 ms was 72,7%, and for patients with QRS<150 ms — 36,8% (Log-rank test p=0,031).Conclusion. In HF patients, PR interval prolongation (≥200 ms) is associated with long-term mortality increase. The highest survival rates were observed in patients with PR<200 ms and QRS≥150 ms. In patients with QRS≥150 ms, the presence of PR≥200 ms should be considered as an additional criterion for CRT.

T-cell clonality in peripheral blood as a predictor of progression to systemic treatment in patients with stage IB mycosis fungoides (MF).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19538-e19538
Author(s):  
Suravi Raychaudhuri ◽  
Charli-Joseph Yann ◽  
Michelle Mintz ◽  
Laura Pincus ◽  
Chiung-Yu Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Systemic Treatment ◽  
Rank Test ◽  
P Value ◽  
Advanced Stage ◽  
Stage Ib ◽  
Log Rank Test ◽  
Secondary Outcomes

e19538 Background: A major unmet clinical need in the care of early-stage MF patients is the identification of those with a high risk of failing skin directed therapy or progressing to advanced disease. Herein, we inquired if the identification of a clonal T-cell receptor (TCR) gene rearrangement by PCR in peripheral blood could predict the clinical outcome, particularly the need for systemic treatment, in patients with stage IB MF. Methods: This is a retrospective cohort study of patients with stage IB MF who underwent peripheral blood TCR clonality analysis by PCR. The primary outcome of the study was time from diagnosis to initiation of systemic treatment. Secondary outcomes were: (1) time to progression to advanced-stage disease (stages IIB-IV) and (2) overall survival. Patients were censored at time of last clinical follow up. Log rank test was used to compare the survival distributions of the two groups; p value < 0.05 was considered significant. Results: From May 2014 to October 2019, 56 consecutive stage IB pts with > 6 months follow up were included in this analysis. Peripheral blood TCR clonality status was available in 42 patients: 18 pts had a positive TCR clone and 24 did not. Median follow up time was 36 months (range 8.5 – 198 months). At 3 years, 39% of patients with peripheral clone had progressed to systemic treatment versus 8% of those without a peripheral clone (log rank test, p-value = 0.003). For the secondary outcomes, at 3 years 17% of patients with peripheral clone had progressed to advanced stage versus 4% of those without (log rank test, p-value = 0.10); 5% of patients with peripheral clone had died versus 0% of those without (log rank test, p-value = 0.03). Conclusions: Detection of a predominant TCR clone by PCR in the peripheral blood is an important prognostic marker in the initial workup of MF, as its presence is highly correlated with subsequent progression to systemic treatment and death. If this finding is validated, it can be used to risk stratify and individualize therapy for MF patients.[Table: see text]

Biologics registries

2013 ◽  
pp. 257-263
Author(s):  
David Isenberg ◽  
Angela Zink
Keyword(s):  
Rheumatoid Arthritis ◽  
Life Experience ◽  
Real Life ◽  
Cancer Development ◽  
Controlled Trials ◽  
Side Effect Profile ◽  
Risk Of Infection ◽  
Biologic Drugs ◽  
Double Blind

Double-blind controlled trials undertaken over the past two decades have established the short-term effectiveness and side-effect profile of biologic drugs for patients with rheumatoid arthritis and related diseases. However, the development of biologics registers to capture ’real-life experience’ and explore long-term effectiveness and complications is equally important. In this chapter, we demonstrate how these registers have identified long-term joint benefits, a reduction in cardiovascular mortality, reassurance concerning fears about cancer development, and a balanced view of the risk of infection.

Long-Term Reduction in Sperm Count After Chemotherapy With and Without Radiation Therapy for Non-Hodgkin's Lymphomas

1993 ◽  
Vol 11 (5) ◽  
pp. 1007-1007 ◽  
Author(s):  
Rodger M. Pryzant ◽  
Marvin L. Meistrich ◽  
Gene Wilson ◽  
Barry Brown ◽  
Peter McLaughlin
Keyword(s):  
Radiation Therapy ◽  
Clin Oncol ◽  
Sperm Count ◽  
Rank Test ◽  
Log Rank Test ◽  
Hodgkin's Lymphomas

The last sentence of the Results section of the February 1993 report "Long-Term Reduction in Sperm Count After Chemotherapy With and Without Radiation Therapy for Non-Hodgkin's Lymphomas" by Pryzant et al (J Clin Oncol 11:239–247, 1993) should have read: "The recovery of those patients who received less than 9.5 g/m2 of cyclophosphamide was significantly greater than those who received more than 9.5 g/m2 of cyclophosphamide (P = .00092, log-rank test)." The unit of measure for cyclophosphamide in the legend for Fig 4 and in the next to last paragraph of the Discussion should have been g/m2.

scholarly journals P737 Ustekinumab induction effectiveness in Crohn’s disease in a real-life cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S590-S591
Author(s):  
E Sánchez Rodríguez ◽  
F Mesonero Gismero ◽  
A López sanroman
Keyword(s):  
Biological Therapy ◽  
Treatment Time ◽  
Real Life ◽  
Delayed Response ◽  
Faecal Calprotectin ◽  
Tract Involvement ◽  
Maintenance Of Remission ◽  
Term Maintenance

Abstract Background Evaluation of Ustekinumab induction therapy is generally performed at week 16. Our aim was to evaluate if a delayed response may be expected beyond that time. Methods Retrospective study including patients with CD who received Ustekinumab since 1 June 2017 to 1 May 2019. Iv induction dose was based on weight while maintenance was conducted with 90 mg subcutaneous every 8 weeks. Results Twenty-five patients (52% male) were enrolled, of whom 28% (7/25) had ileal, 28(7/25) colonic, 44% (11/25) ileocolonic and 8% (2/25) upper tract involvement. Sixty-eight per cent (17/25) presented an inflammatory, 16% (4/25) a stricturing and 16% (4/25) a penetrating behaviour. Perianal disease was diagnosed in 20% of patients (5/25). All patients 100% (25/25) had previously taken immunosuppressants and 96% (24/25) biological therapy (mean 1.8 ± 0.87 (0–3) per patient): 36% (9/25) one, 36% (9/25) two and 24% (6/25) three agents. Ustekinumab was prescribed for achieving remission in 92% (23/25) of the patients, fistulising disease in 4% (1/25) and for maintenance of remission in the same percentage. Follow-up was 373.16 ± 182.53(59–683) days. Discontinuation rate was 24% (6/25), due to primary failure in 100% (6/6). For those who stopped the drug, average treatment time was 137.17 ± 95.11(61–1320) days whereas that of those who continued was 346.84 ± 192.10(32–669) days. Clinical response was evaluated at week 8, week 14–16, week 22–24 and during long-term maintenance (Table 1). All comparisons were statistically significant (p &lt; 0.05). We recorded Harvey-Bradshaw index(H-B), CRP and faecal calprotectin (FC) before induction with ustekinumab, at weeks 14–16, at weeks 22–24 and during maintenance. Results are presented in Table 2. Conclusion Evaluation of induction effectiveness at week 22–24 may allow to rescue those patients who present a delayed response to UST. During a 373.16 days follow-up, loss of response to Ustekinumab is low.

scholarly journals Comparison of Long-Term Results After Nephron-Sparing Surgery and Radical Nephrectomy in Treating 4- to 7-cm Renal Cell Carcinoma

Medicina ◽  
2013 ◽  
Vol 49 (5) ◽  
pp. 36 ◽  
Author(s):  
Daimantas Milonas ◽  
Giedrius Skulčius ◽  
Ruslanas Baltrimavičius ◽  
Stasys Auškalnis ◽  
Marius Kinčius ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Radical Nephrectomy ◽  
Nephron Sparing Surgery ◽  
Rank Test ◽  
Cancer Specific Survival ◽  
Log Rank Test ◽  
Nephron Sparing

Objective. The aim of our study was to compare long-term oncological outcomes following nephron-sparing surgery (NSS) and radical nephrectomy (RN) for renal cell carcinoma (RCC) 4 to 7 cm in diameter. Material and Methods. The study included patients who underwent RN or NSS for RCC 4 to 7 cm in diameter between 1998 and 2009. The studied groups were compared with respect to the patients’ age, sex, physical status according to the American Society of Anesthesiologists Physical classification, histological type, stage, tumor size, grade, duration of the operation, and complications. Survival was established using the Kaplan-Meier method. The risk factors for survival were analyzed using a multivariate Cox regression model. Results. During the study, 351 patients underwent surgery: 317 patients (90.3%) underwent RN, and 34 (9.7%), NSS. The compared groups differed with respect to tumor size (P=0.001) and stage (P=0.006). The overall estimated 12-year survival was 53.7% after RN and 55.2% after NSS (log-rank test P=0.437). The 12-year cancer-specific survival in the RN and NSS groups was 69.6% and 80.6%, respectively (log-rank test P=0.198). Pathological stage and patients’ age were the major factors affecting both overall and cancer-specific survival. The type of surgery (NSS or RN) had no effect on survival. Conclusions. Our study showed that nephron-sparing surgery is a safe technique compared with radical nephrectomy that ensures good oncological control in the treatment of renal cell carcinoma measuring 4 to 7 cm and may be proposed as the treatment of choice for renal tumors not only up to 4 cm, but also 4 to 7 cm in size.

scholarly journals Assessing Long-Term Survival Benefits of Immune Checkpoint Inhibitors Using the Net Survival Benefit

2019 ◽  
Vol 111 (11) ◽  
pp. 1186-1191 ◽  
Author(s):  
Julien Péron ◽  
Alexandre Lambert ◽  
Stephane Munier ◽  
Brice Ozenne ◽  
Joris Giai ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Survival Benefit ◽  
Rank Test ◽  
Cure Rate ◽  
Term Survival ◽  
Long Term Survival ◽  
Delayed Treatment ◽  
Net Survival ◽  
Log Rank Test

Abstract Background The treatment effect in survival analysis is commonly quantified as the hazard ratio, and tested statistically using the standard log-rank test. Modern anticancer immunotherapies are successful in a proportion of patients who remain alive even after a long-term follow-up. This new phenomenon induces a nonproportionality of the underlying hazards of death. Methods The properties of the net survival benefit were illustrated using the dataset from a trial evaluating ipilimumab in metastatic melanoma. The net survival benefit was then investigated through simulated datasets under typical scenarios of proportional hazards, delayed treatment effect, and cure rate. The net survival benefit test was computed according to the value of the minimal survival difference considered clinically relevant. As comparators, the standard and the weighted log-rank tests were also performed. Results In the illustrative dataset, the net survival benefit favored ipilimumab [Δ(0) = 15.8%, 95% confidence interval = 4.6% to 27.3%, P = .006]. This favorable effect was maintained when the analysis was focused on long-term survival differences (eg, >12 months, Δ(12) = 12.5% (95% confidence interval = 4.4% to 20.6%, P = .002). Under the scenarios of a delayed treatment effect and cure rate, the power of the net survival benefit test compared favorably to the standard log-rank test power and was comparable to the power of the weighted log-rank test for large values of the threshold of clinical relevance. Conclusion The net long-term survival benefit is a measure of treatment effect that is meaningful whether or not hazards are proportional. The associated statistical test is more powerful than the standard log-rank test when a delayed treatment effect is anticipated.

scholarly journals Long-term effect of azithromycin in bronchiolitis obliterans syndrome

2019 ◽  
Vol 6 (1) ◽  
pp. e000465
Author(s):  
C.Tji-Joong Gan ◽  
Chris Ward ◽  
Gerard Meachery ◽  
James Laurence Lordan ◽  
Andrew J Fisher ◽  
...  
Keyword(s):  
Overall Survival ◽  
Placebo Group ◽  
Bronchiolitis Obliterans ◽  
Bronchiolitis Obliterans Syndrome ◽  
Term Effect ◽  
Rank Test ◽  
Open Label ◽  
Log Rank Test ◽  
Long Term Effect

IntroductionAzithromycin stabilises and improves lung function forced expiratory volume in one second (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV1, BOS progression and survival .MethodsEligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV1, BOS free progression and overall survival.ResultsFEV1 in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV1 decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74).DiscussionLong-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV1 decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.

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