26.4 Pharmacogenomics in Clinical Practice: Does It Always Predict Clinical Response?

2017 ◽  
Vol 56 (10) ◽  
pp. S39
Author(s):  
Osman Qureshi
Keyword(s):  
Clinical Practice ◽  
Clinical Response

scholarly journals AB0304 IMMUNOGENICITY OF BIOLOGIC DRUGS IN THE CLINICAL PRACTICE IN THE BULGARIAN POPULATION OF PATIENTS SUFFERING FROM RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1451.3-1451
Author(s):  
K. Kraev ◽  
M. Geneva-Popova ◽  
S. Popova
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Clinical Response ◽  
Neutralizing Antibodies ◽  
Tnf Alpha ◽  
Drug Bioavailability ◽  
Drug Induced ◽  
Etanercept Treatment ◽  
Markers Of Inflammation

Background:Biological drugs are protein derivatives that, as such, are highly immunogenic. In recent years there have been many conflicting opinions about the role of drug immunogenicity in clinical practice.Objectives:To evaluate the drug immunogenicity of TNF-alpha blocking drugs (etanercept and adalimumab) used to treat patients with rheumatoid arthritis. To determine whether their presence can alter the effect of treatment and to evaluate their role in the clinical practice of rheumatologists.Methods:121 patients with rheumatoid arthritis, as well as 31 healthy controls, similar in sex and age, were examined. They were all monitored at 0, 6, 12 and 24 months from the start of TNF-alpha blocker treatment. Demographics, vital signs, markers of inflammation such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity indices were examined at each visit, respectively. Drug-induced neutralizing antibodies, as well as drug bioavailability in patients treated with adalimumab, were examined by ELISA.Results:Drug-induced neutralizing antibodies to adalimumab were detected in 11.57% of patients at 6 month, in 17.64% of patients at 12 month, and 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not detected at 6 months, at 7.77% at 12 months, at 9.63% of patients at 24 months. Of the adalimumab patients who were having drug-induced antibodies, 92.59% had low drug bioavailability, while the remaining 7.41% of patients showed normal drug bioavailability despite the presence of drug-induced neutralizing antibodies. In terms of worsening of the disease activity, a positive correlation was found with the presence of drug antibodies - Pearson Correlation = 0.701, p = 0.001. Patients with poor clinical response and available drug antibodies receiving adalimumab were slightly more than those treated with etanercept at 12 and 24 months but the difference is non-significant-U = 0.527, p> 0.05 and U = 0.623, p> 0.05, respectively.Conclusion:Presence of drug-induced neutralizing antibodies in patients treated with adalimumab and etanercept has been associated with poor clinical response and worsening of the patient’s condition. Testing of drug-induced neutralizing antibodies as well as the drug bioavailability of the drug used can be used as reliable biomarkers in clinical rheumatology.References:[1]Benucci M., F.Li Gobbi, M. Meacii et al., “Antidrug antibodies against TNF-blocking agents: correlations between disese activity, hypersensitivity reactions, and different classes of immunoglobulins”, Biologics and Targets and Therapy, 2015: 9 7 -2.[2]Chen D., Y. Chen, W. Tsai et al., “ Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis”, Ann Rheum Dis. 2015 Mar; 74 (3).[3]Kalden J. and H. Schulze-Koops, “ Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment ”, Nature Reviews Rheumatology, 2017 volume 13, 707–718.[4]Wolf-Henning Boehnck, N. Brembilla, “ Immunogenicity of biological therapies: causes and consequences, ” Expert Review of Clinical Immunology, Vol 14, 2018, Issue 6, 513-523Disclosure of Interests:None declared

Prediction of Clinical Response to Antidepressants in Patients with Depression: Neurophysiology in Clinical Practice

2007 ◽  
Vol 38 (2) ◽  
pp. 74-77 ◽  
Author(s):  
Oliver Pogarell ◽  
Georg Juckel ◽  
Christine Norra ◽  
Gregor Leicht ◽  
Susanne Karch ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Response

Clozapine plasma levels and dosing strategies in patients with treatment-refractory schizophrenia

1997 ◽  
Vol 14 (3) ◽  
pp. 85-88 ◽  
Author(s):  
Peter F Buckley ◽  
Philip Cola ◽  
Mitsuru Hasegawa ◽  
Christine Lys ◽  
Paul Thompson
Keyword(s):  
Clinical Practice ◽  
Partial Response ◽  
Clinical Response ◽  
Clinical Improvement ◽  
Plasma Levels ◽  
Major Metabolite ◽  
The Other ◽  
Adequate Response ◽  
Dosing Strategies ◽  
Treatment Refractory

AbstractObjective: To determine the effect on clinical response to clozapine of increasing the plasma levels of clozapine and its major metabolite N-desmethylclozapine in 19 patients with schizophrenia who had plasma clozapine levels ≤ 370ng/ml, a level previously determined to identify patients who were unlikely to have an adequate response to clozapine.Method: The dosage of clozapine was increased by 20% in 11 patients and left unaltered in the other eight patients. Clozapine and N-desmethylclozapine plasma levels were measured after six weeks at the higher dose.Results: Nine of the 11 patients in whom clozapine dosage was increased subsequently achieved plasma clozapine levels ≥ 370ng/ml. However, in this group of patients who already had partially responded to clozapine, increasing the dosage of clozapine did not produce additional clinical improvement.Conclusion: Clozapine plasma levels are useful in clinical practice to guide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels ≥ 370ng/ml is unlikely to produce further improvement in patients who have already achieved a partial response to clozapine at plasma levels ≤ 370ng/ml.

scholarly journals EXPERIENCE OF TOFACITINIB USING IN THERAPY OF ULCERATIVE COLITIS IN REAL CLINICAL PRACTICE

2019 ◽  
Vol 18 (4) ◽  
pp. 86-99
Author(s):  
E. A. Belousova ◽  
Вю I. Abdulganieva ◽  
O. P. Alekseeva ◽  
I. G. Bakulin ◽  
O. V. Vasilyeva ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Response ◽  
Clinical Improvement ◽  
Clinical Remission ◽  
Therapeutic Option ◽  
Mucosal Healing ◽  
Induction Treatment ◽  
Extraintestinal Manifestations ◽  
Biological Drugs ◽  
Real Clinical Practice

AIM: to demonstrate the first Russian experience with the use of tofaciminib (TOFA) for the treatment of moderate and severe UC in real clinical practice.PATIENTS AND METHODS: eighty-five patients with UC (aged 41.38±14.69 years, average disease duration 9.55±5.27 years, mild UC – 3.5%, moderate UC – 41.2%, severe – 52.9%, acute severe UC – 2.6%), resistant to corticosteroid therapy (36.5%) and biological agents (61.2%), were prescribed with TOFA at an induction dose of 10 mg 2 times a day, followed by a decrease in the dose to a maintenance dose (5 mg 2 times a day). Early clinical response, clinical and endoscopic remission, prevalence and dynamic of extraintestinal manifestations were assessed at 8 and 12 weeks of treatment, as well as safety and tolerability.RESULTS: Sixty-eight (80.0%) patients completed induction treatment with TOFA for 8 weeks, other patients continue to receive TOFA. A quick response within one week was detected in 41 (50.6%) patients, on average, on the 5th day of therapy. At the end of induction, 52 (76.5%) patients achieved clinical remission, 3 (4.4%) achieved a clinical response, 13 (19.1%) patients showed no positive changes. Of the 53 patients observed over 12 weeks, 41 (77.4%) had clinical remission, 6 (11.3%) had clinical improvement, and 6 (11.3%) patients had no response to the treatment. The changes of extraintestinal manifestations were positive: 55.2% of patients at week 8 and 77.8% of patients at week 12 showed clinical improvement, mainly in relation to the joint syndrome. One episode of herpes zoster infection, one case of anemia, were identified dur-ing 12 weeks of follow-up.CONCLUSION: TOFA in UC is effective in achieving a rapid clinical response, clinical remission and mucosal healing in patients who do not adequately respond to therapy with basic as well as biological drugs. Tofacitinib is an effective and safe therapeutic option for this challenging patient population.

Golimumab trough levels, antidrug antibodies and clinical response in patients with rheumatoid arthritis treated in daily clinical practice

2014 ◽  
Vol 73 (12) ◽  
pp. 2217-2219 ◽  
Author(s):  
Eva L Kneepkens ◽  
Chamaida Plasencia ◽  
Charlotte LM Krieckaert ◽  
Dora Pascual-Salcedo ◽  
Desiree van der Kleij ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Clinical Response ◽  
Daily Clinical Practice ◽  
Antidrug Antibodies ◽  
Trough Levels

scholarly journals Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice

2020 ◽  
Vol 92 (2) ◽  
pp. 67-73
Author(s):  
M. V. Shapina ◽  
B. A. Nanaeva
Keyword(s):  
Clinical Practice ◽  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Clinical Remission ◽  
Line Therapy ◽  
Steroid Dependent ◽  
Endoscopic Remission ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Real Clinical Practice

Vedolizumab is currently the only selective biological drug for the treatment of inflammatory bowel diseases (IBD). Its effectiveness and safety has been shown in clinical trials. This article presents the experience of using vedolizumab in real clinical practice in patients with various forms of ulcerative colitis (UC) and Crohns disease (CD). Materials and methods.96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated). Results.After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months 62.5%, endoscopic remission 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%). Conclusions.Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

scholarly journals Efficacy and safety of tofacitinib in moderate and severe ulcerative colitis in real clinical practice: three years of observation

2021 ◽  
pp. 20-29
Author(s):  
O. V. Knyazev ◽  
A. V. Kagramanova ◽  
A. A. Lishchinskaya ◽  
I. A. Li ◽  
D. V. Podolskaya ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Clinical Response ◽  
Clinical Remission ◽  
Cumulative Effect ◽  
Early Response ◽  
Mucosal Healing ◽  
Efficacy And Safety ◽  
One Year ◽  
Real Clinical Practice

Introduction. Tofacitinib is the first member of a new class of targeted synthetic anti-inflammatory drugs for the treatment of ulcerative colitis (UC). The article presents a three-year Russian experience of tofacitinib use for the treatment of moderate and severe UC.Aim of the study. To evaluate the efficacy and safety of tofacitinib therapy in real clinical practice in moderate to severe UC patients during three years of follow-up.  Methods. The study included 56 patients with UC who had moderate (60.7%) and severe (35.8%) states of disease, the total lesion was diagnosed in 67.8%, and extraintestinal manifestations in 57.1% of patients. Early achievement of clinical response, clinical and endoscopic, corticosteroid-free remission, and safety were evaluated.Results. Early response to tofacitinib therapy was obtained in 47 (83.9%) patients. Clinical remission was achieved in 36 (64.3%) at week 8 of therapy and clinical response was achieved in 13 (23.2%) patients. The majority of patients who achieved clinical remission at weeks 8 and 12 achieved healing of colon mucosa at week 24. Clinical and endoscopic remission rates after 24 weeks – 44 (78.6%) patients, clinical response in 7 (12.5%) patients, 5 (8.9%) did not respond to TFCB therapy. Corticosteroidfree remission was 77.6%. After 2 years of tofacitinib therapy, remission of UC was maintained in 46 (82.1%). After 36 months, remission of UC was maintained in 45 (80.3%) of the 56 patients who had been started on tofacitinib therapy. The cumulative effect of survival in the treatment of tofacitinib in UC was 87.5% after 6 months and persisted for one year, 82.1% after 2 years, and 80.3% after 3 years.Conclusions. The administration of tofacitinib in UC is effective in achieving rapid clinical response, clinical remission, and mucosal healing in patients who do not respond well to biological therapy. 

scholarly journals Long-Term Response Rates to Infliximab Therapy for Crohn’s Disease in an Outpatient Cohort

2009 ◽  
Vol 23 (5) ◽  
pp. 348-352 ◽  
Author(s):  
Christopher W Teshima ◽  
Adrienne Thompson ◽  
LeRose Dhanoa ◽  
Levinus A Dieleman ◽  
Richard N Fedorak
Keyword(s):  
Crohn’S Disease ◽  
Clinical Practice ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Outcomes ◽  
Safety Data ◽  
Real Life ◽  
Response Rates ◽  
Infliximab Therapy

BACKGROUND: Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.OBJECTIVE: To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic.METHODS: A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease.RESULTS: One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection.CONCLUSION: Patients treated with infliximab therapy for luminal Crohn’s disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.

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