Adalimumab in the Treatment of Psoriasis: Pooled Efficacy and Safety Results from Three Pivotal Studies

2009 ◽  
Vol 13 (5_suppl) ◽  
pp. S58-S66 ◽  
Author(s):  
Kim Papp ◽  
Martin Okun ◽  
Ronald Vender
Keyword(s):  
Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Severity Index ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Psoriasis Area Severity Index ◽  
Treatment Groups ◽  
Efficacy Measure ◽  
Efficacy Measures ◽  
Necrosis Factor

Background: Adalimumab, a fully human monoclonal antibody, binds to and neutralizes tumor necrosis factor. Objective: To provide an integrated review of efficacy and safety from adalimumab clinical trials in psoriasis. Methods: Pooled analyses were conducted of three placebo-controlled clinical trials of adalimumab (40 mg every other week) in psoriasis patients. The primary efficacy measure was the Psoriasis Area Severity Index (PASI). The Physician's Global Assessment (PGA) was also assessed. Results: At Week 16, mean percentage PASI improvement was 78.3% for adalimumab-treated patients versus 15.1% for placebo-treated patients. A PGA of “Clear” or “Minimal” was achieved in 63.4% of adalimumab-treated patients versus 5.1% of placebo-treated patients. The response to adalimumab was rapid, with significant improvements for adalimumab-treated patients in most efficacy measures by Week 4. Adverse event incidence was similar between treatment groups and consistent with adalimumab safety profiles in other indications. Conclusion: Adalimumab improved psoriasis and was generally safe and well-tolerated.

Anatomy of a trial

PEDIATRICS ◽  
1977 ◽  
Vol 60 (6) ◽  
pp. 932-934
Author(s):  
Neil A. Holtzman
Keyword(s):  
Clinical Trials ◽  
Clinical Situation ◽  
Enzyme Deficiency ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Biochemical Alterations ◽  
New Treatments ◽  
The Way

Efficacy and safety of new treatments can seldom be predicted with certainty. Even when it addresses biochemical alterations, a therapy may not improve the clinical situation. The low-phenylalanine diet for phenylketonuria (PKU), for instance, followed logically from the discovery of an enzyme deficiency, but the diet's effectiveness in preventing retardation in asymptomatic infants was still in doubt a decade after it was introduced. Studies in which some subjects are not treated can often establish the benefits and risks of therapy. Many obstacles, however, lie in the way of controlled clinical trials despite the advantage they offer. The PKU story exemplifies the issues.

Antifungal Prophylaxis in Immunocompromised Hosts

1993 ◽  
Vol 27 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Stan Reents ◽  
S. Diane Goodwin ◽  
Vipul Singh
Keyword(s):  
Clinical Trials ◽  
Antifungal Prophylaxis ◽  
Nausea And Vomiting ◽  
Fungal Colonization ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Immunocompromised Hosts ◽  
The Relationship

OBJECTIVE: To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. DATA EXTRACTION: Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. RESULTS: Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. CONCLUSIONS: Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.

scholarly journals A Nonimmunosuppressant Approach on Asia Psoriasis Subjects: 5-Year Followup and 11-Year Data Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-11
Author(s):  
Tony Yuqi Tang
Keyword(s):  
Severity Index ◽  
Adverse Event Reporting ◽  
Efficacy And Safety ◽  
Psoriasis Area Severity Index ◽  
Telephone Interviews ◽  
Liver Function Testing ◽  
Pasi Score ◽  
Psoriasis Lesion ◽  
Function Testing ◽  
Monthly Visit

Mono- or combine immunosuppressants are commonly used for psoriasis; however the side effect caused by potent systemic immunosuppressants frequently incurred; moreover the inflammation flares up shortly after immunosuppressants are discontinued. An alternative nonimmunosuppressive therapy was introduced to psoriasis subjects. A retrospective observational study consisted of 1583 psoriasis patients who were treated with Herose Psoria capsule 1440 mg three times daily at two clinical centres, one in China, the other in Singapore, from 1 January 2000 to 1 January 2011. Psoriasis lesion evolution was photographed at monthly visit, and efficacy and safety were assessed using psoriasis area severity index PASI score grading, renal and liver function testing, and adverse event reporting and supplemented by information obtained during targeted telephone interviews. The effectiveness of Herose on psoriasis was inversely associated to prior immunosuppressants exposure (r=0.9154), significant improvements occurred in non-immunosuppressants subjects, and complete clearance was achieved in 8 months (87.5%, 14 of 16); the wavelike evolution of psoriatic lesion appeared in prior immunosuppressants subjects.

scholarly journals Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Junzhu Deng ◽  
Haiyang Hu ◽  
Feihong Huang ◽  
Chunlan Huang ◽  
Qianqian Huang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Platelet Response ◽  
Controlled Clinical Trials ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Thrombopoietin Receptor

Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs via indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the Medline, PubMed, Embase, the Cochrane Library, and Web of Science databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 109/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.

scholarly journals Effectiveness and safety of secukinumab for psoriasis in real-world practice: analysis of subgroups stratified by prior biologic failure or reimbursement

2019 ◽  
Vol 10 ◽  
pp. 204062231984375 ◽  
Author(s):  
Tzong-Yun Ger ◽  
Yu-Huei Huang ◽  
Rosaline Chung-yee Hui ◽  
Tsen-Fang Tsai ◽  
Hsien-Yi Chiu
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Real Life ◽  
Severity Index ◽  
Improvement Rate ◽  
Lower Baseline ◽  
The Mean ◽  
Factor Α ◽  
Necrosis Factor ◽  
Retrospective Multicenter Study

Background: Little is known about the treatment outcomes of secukinumab in clinical practice, which differ from those in clinical trials. The effectiveness of biologics may differ in psoriasis patients with previous biologics exposure. The objective of this study was to investigate the real-world effectiveness and safety of secukinumab therapy and analyze subgroups stratified by reimbursement or prior biologic failure. Methods: This retrospective multicenter study collected data from a cohort of 118 consecutive patients who received secukinumab treatment between December 2015 and March 2018. Effectiveness was evaluated by degree of improvement in the Psoriasis Area and Severity Index (PASI) scores. Adverse events and reasons for discontinuation were also recorded. Results: The mean PASI improvement rate at weeks 4, 12, 24, and 36 was 63.5%, 77.7%, 78.7%, and 76.0%, respectively. Compared with reimbursed patients, nonreimbursed patients had a significantly lower baseline PASI and a shorter mean disease duration of psoriasis; they were more frequently biologic-naïve, had used less prior traditional antipsoriatic drugs and were more likely to be treated with secukinumab 150 mg. The effectiveness of secukinumab in nonreimbursed patients was superior despite higher discontinuation rates. Compared with patients without prior biologic failure, patients with prior biologic failure had a significantly lower mean PASI improvement at weeks 12, 24, 36, and 48. The decline in response rates to secukinumab tended to be more pronounced for patients who failed ustekinumab than tumor necrosis factor-α inhibitors. Moreover, the number of prior biologic failures was associated with a decreased response rate and increased likelihood of secondary loss of effectiveness of secukinumab therapy. Conclusion: In a real-life clinical setting, the characteristics of nonreimbursed patients receiving secukinumab treatment differed from those of reimbursed patients. The PASI improvement for secukinumab was substantial but lower than that in clinical trials. The number and classes of prior biologic failures impact the treatment response to secukinumab.

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