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The Cochrane Database of Systematic... Dec 2017Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis.
OBJECTIVES
To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety.
SEARCH METHODS
We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent.
DATA COLLECTION AND ANALYSIS
Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing.
MAIN RESULTS
We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk.Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90.In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents.At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments.Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence).We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution.Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability.Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90.Information on quality of life was often poorly reported and was absent for a third of the interventions.
AUTHORS' CONCLUSIONS
Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.
Topics: Adult; Antibodies, Monoclonal; Chronic Disease; Humans; Immunosuppressive Agents; Network Meta-Analysis; Psoriasis; Randomized Controlled Trials as Topic; Remission Induction; Tumor Necrosis Factor-alpha
PubMed: 29271481
DOI: 10.1002/14651858.CD011535.pub2 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
Archives of Dermatology Apr 2012To summarize the current state of evidence for combination topical and systemic therapies for mild to severe psoriasis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the current state of evidence for combination topical and systemic therapies for mild to severe psoriasis.
DATA SOURCES
We performed a systematic search for all entries in PubMed, CINAHL, Cochrane Review, and EMBASE related to combination treatments for psoriasis through July 2010.
STUDY SELECTION
We included randomized controlled trials that reported proportion of disease clearance or mean change in clinical severity score (or provided these data through communication with study authors) for efficacy of a combination treatment for psoriasis compared with 1 or more corresponding monotherapies.
DATA EXTRACTION
Study data were extracted by 3 independent investigators, with disagreement resolved by consensus. The proportion of patients who achieved clearance, definition of clearance, means and standard deviations for baseline disease symptom score and final disease symptom score, and major design characteristics were extracted for each study.
DATA SYNTHESIS
Combination treatments consisting of vitamin D derivative and corticosteroid, vitamin D derivative and UV-B, vitamin A derivative and psoralen-UV-A, vitamin A derivative and corticosteroid, vitamin A derivative and UV-B, corticosteroid and hydrocolloid occlusion dressings, UV-B and alefacept, and vitamins A and D derivatives were more effective than 1 or more monotherapies using the likelihood of clearance as the outcome. Blinding status and potency of the corticosteroid treatment used were significant sources of heterogeneity between studies.
CONCLUSIONS
The results demonstrate the need for additional long-term trials with standardized outcome measures to evaluate the efficacy and adverse effects of combination therapies for psoriasis and highlight the possible effects of trial design characteristics on results.
Topics: Adrenal Cortex Hormones; Balneology; Bandages, Hydrocolloid; Combined Modality Therapy; Dermatologic Agents; Drug Therapy, Combination; Humans; Immunosuppressive Agents; PUVA Therapy; Psoriasis; Ultraviolet Therapy; Vitamin A; Vitamin D; Vitamins
PubMed: 22184718
DOI: 10.1001/archdermatol.2011.1916 -
BMJ Clinical Evidence Jan 2009Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. (Review)
Review
INTRODUCTION
Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.
Topics: Adrenal Cortex Hormones; Animals; Dermatologic Agents; Humans; Phototherapy; Psoriasis; Ultraviolet Rays; Ultraviolet Therapy
PubMed: 19445765
DOI: No ID Found -
Annals of the Rheumatic Diseases Jun 2008Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs) and low-cost disease-modifying anti-rheumatic drugs (DMARDs) studied in less detail. We compared their efficacy and toxicity in a systematic review.
METHODS
We searched Medline, PubMed and EmBase (1966-2006) for RCTs in PsA. We included RCTs that were randomised, placebo-controlled, in English, involved current treatments and only enrolled PsA patients. Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events. RCTs were compared using risk ratios (RR) with 95% confidence intervals (CI).
RESULTS
We identified 32 potentially relevant RCTs; 14 were excluded because they involved unused agents, were unblinded, were not placebo-controlled and enrolled patients with other diseases. 18 studies were included in the meta-analysis assessing DMARD monotherapy (11), DMARD combinations (one), TNF inhibitors (five) and alefacept (one). Treatment was more effective than placebo (RR = 0.35; 95% CI 0.25, 0.49) but caused more toxicity (RR = 2.33; 95% CI 1.61, 3.37). There was evidence that gold, sulfasalazine, leflunomide and TNF inhibitors were effective; gold and TNF inhibitors showed the largest effect sizes; TNF inhibitors had the best efficacy/toxicity ratio (number needed to harm/number needed to treat = 0.25); tolerability was least with gold and leflunomide.
CONCLUSIONS
Efficacy/toxicity ratios were highest with TNF inhibitors followed by leflunomide, gold and sulfasalazine. Gold, though effective, has excessive toxicity and sulfasalazine, though of low toxicity, was also relatively ineffective.
Topics: Alefacept; Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Isoxazoles; Leflunomide; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Risk Assessment; Sulfasalazine; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 17827183
DOI: 10.1136/ard.2007.072652 -
PloS One 2012While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and... (Review)
Review
OBJECTIVES
While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment) with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment.
DATA SOURCES AND STUDY SELECTION
We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept.
DATA SYNTHESIS
A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited.
CONCLUSION
Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent results in superior efficacy over interrupted therapy. The decision to use off-label dosing needs to account for both benefits and risks and be individualized to patients' disease severity, quality of life, and existence of comorbidities.
Topics: Drug Approval; Drug Dosage Calculations; Humans; Off-Label Use; Psoriasis; Safety; Withholding Treatment
PubMed: 22509259
DOI: 10.1371/journal.pone.0033486 -
Medicine Oct 2021Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.
OBJECTIVE
To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.
DATA SOURCES
A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.
STUDY ELIGIBILITY CRITERIA
The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).
RESULTS
The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18-1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02-1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11-2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31-4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07-2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64-2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89-5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20-10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22-11.34; I2 = 0%) did not.
LIMITATIONS
Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.
SYSTEMATIC REVIEW REGISTRATION NUMBER
INPLASY202110027.
Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Psoriatic; Biological Factors; Female; Herpes Zoster; Humans; Immunosuppression Therapy; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 34622837
DOI: 10.1097/MD.0000000000027368 -
Archives of Dermatological Research Nov 2012There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled... (Meta-Analysis)
Meta-Analysis Review
Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment.
There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled trials. The improvements observed in placebo groups within trials examining psoriasis treatments may be partially due to study design and implementation. We conducted a systematic review of randomized placebo-controlled trials assessing the efficacy of biologics in the treatment of psoriasis and psoriatic arthritis to evaluate rates of placebo and active drug responders to determine specific factors within study design that may contribute to placebo responses. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, ustekinumab, alefacept, and efalizumab that utilized Psoriasis Area Severity Index as an outcomes measure. We compared the rates of the placebo treatment arm versus the active drug arm achieving 75 % improvement of Psoriasis Area Severity Index. 31 trials involving 8285 active treatment and 3999 placebo patients were included. Rates of placebo responders (4.14 %) were significantly lower than active drug responders (48.4 %). The overall odds ratio calculated was 23.94 (p < 0.0001, 95 % CI 16.02-35.76). Binomial regression models showed that treatment indication, randomization fraction, a PASI inclusion requirement, and the time period of outcomes measure documentation affect placebo responses. Placebo responses seen in randomized controlled trials evaluating biologics in the treatment of psoriasis are not likely due to a physiologic mechanism, but may be secondary to chronic disease course and factors of clinical trial design and implementation.
Topics: Arthritis, Psoriatic; Biological Products; Humans; Psoriasis; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 22843024
DOI: 10.1007/s00403-012-1266-9 -
The Journal of Rheumatology Jul 2006Alefacept, efalizumab, etanercept, and infliximab are currently approved for the treatment of adults with moderate to severe plaque psoriasis, and phase 3 trials for... (Review)
Review
Alefacept, efalizumab, etanercept, and infliximab are currently approved for the treatment of adults with moderate to severe plaque psoriasis, and phase 3 trials for adalimumab are ongoing. The high level of evidence from large randomized, double-blind, placebo-controlled clinical studies for each of these biologics allows high-grade recommendations and helps define uncertainties, one of which is longterm safety. For tumor necrosis factor-a blocking agents, safety profiles are available from clinical experience in other indications. In general, biologics are safe and effective in the treatment of psoriasis, with potential to address unmet medical needs. Their distinct profiles allow dermatologists to match the biologic agent to individual characteristics of patients who are candidates for systemic therapy or phototherapy. In this evidence-based review of the literature, we assess the effects on psoriasis of induction therapy with 5 biologics and provide preliminary treatment guidelines.
Topics: Adalimumab; Alefacept; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Clinical Trials as Topic; Etanercept; Humans; Immunoglobulin G; Immunologic Factors; Infliximab; Psoriasis; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Treatment Outcome
PubMed: 16724367
DOI: No ID Found -
The Australasian Journal of Dermatology Feb 2019A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding...
A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.
Topics: Adjuvants, Immunologic; Administration, Intravenous; Administration, Oral; Alopecia; Alopecia Areata; Antidepressive Agents; Biological Products; Complementary Therapies; Glucocorticoids; Humans; Inosine Pranobex; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 30191561
DOI: 10.1111/ajd.12913