A Systematic Review Evaluating the Effectiveness of Several Biological Therapies for the Treatment of Skin Psoriasis

Psoriasis is a chronic inflammatory skin illness that has the potential to manifest at any stage of life, it is most frequently observed in early adulthood. Biological drugs have significantly transformed the landscape of psoriasis treatment through the provision of focused therapy, which effectively mitigates inflammation and regulates the overproduction of skin cells. Notwithstanding the accessibility of these biological drugs, rigorous evaluations that juxtapose their safety and efficacy profiles are necessary. The objective of this study is to conduct a thorough investigation of the relative efficacy of these drugs in alleviating psoriasis symptoms and increasing the quality of life for patients by synthesizing the existing evidence. A comprehensive review was conducted to evaluate and compare the safety and effectiveness of different biochemical medicines utilized in the management of psoriasis. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, the review process was conducted among the available studies. A search was conducted across electronic databases, such as Web of Science, PubMed, and Embase, utilizing a combination of keywords and Mesh phrases pertaining to psoriasis, biological medications, and particular names of pharmaceuticals. In total, 475 studies were ascertained by the preliminary search of the database. After eliminating duplicate research, 358 distinct studies remained. After meticulous screening of titles and abstracts against the predefined inclusion criteria, 281 papers were deemed ineligible and thus excluded. For final inclusion, the whole texts of the remaining 77 studies were evaluated. Forty additional papers were removed during the full-text evaluation for a variety of reasons, including improper research design, or insufficient outcome data. Finally, 37 studies were included in this systematic review since they satisfied all inclusion criteria. The results of the current systematic review showed that all biological medications showed high efficacy in the treatment of skin psoriasis compared with placebo based on the clinical assessment outcomes using different tools such as PASI.


Introduction And Background
Psoriasis is a chronic inflammatory skin illness characterized by a fast accumulation of skin cells, culminating in thick, scaly plaques [1].It can cause substantial physical and psychological anguish and impacts millions of individuals globally [2,3].Psoriasis's precise etiology remains uncertain; nevertheless, it is hypothesized to be the result of an intricate interplay between environmental and genetic influences [4,5].
Psoriasis has considerable variation in prevalence across distinct populations, with global estimates spanning from 0.1% to 3% [6].Although it has the potential to manifest at any stage of life, it is most frequently observed in early adulthood [7].In addition to nails, psoriasis can impact the scalp, elbows, and knees, among other body areas [8].
Biological drugs have significantly transformed the landscape of psoriasis treatment through the provision of focused therapy, which effectively mitigates inflammation and regulates the overproduction of skin cells.Having demonstrated exceptional effectiveness in clinical studies, they have received approval for the treatment of psoriasis.Risankizumab, secukinumab, guselkumab, adalimumab, certolizumab, etanercept, ustekinumab, brodalumab, ixekizumab, tildrakizumab, infliximab, methotrexate, briakinumab, golimumab, and adalimumab are some examples of biological medicines frequently used in the management of psoriasis [9,10].Biological therapies are advised for the treatment of psoriatic disease in all six domains of the disease [11].The primary aim in the therapy of psoriasis is to establish a comprehensive, safe, and efficacious treatment regimen that addresses all of its manifestations [12].Nevertheless, the attainment of this objective is complicated by the diversity of the manifestations.Recent developments in our understanding of the disease's pathogenesis have prompted substantial research and approval of various modes of action, including TNFi (INFLIXIMAB, etanercept, golimumab, certolizumab, and adalimumab); IL-17i (secukinumab, ixekizumab, and brodalumab); and IL-12 and/or IL23i (ustekinumab, guselkumab, Risankizumab, and tildrakizumab).
These pharmaceuticals function via distinct methods of action.As an illustration, ixekizumab, Risankizumab, secukinumab, and guselkumab selectively target interleukin-17A (IL-17A), a protein that is pivotal in the inflammatory mechanism underlying psoriasis [10].Through the inhibition of IL-17A, these pharmaceutical agents aid in the mitigation of inflammation and amelioration of symptoms [10].Additional biological drugs, including infliximab, adalimumab, certolizumab, and etanercept, selectively interact with tumor necrosis factor-alpha (TNF-alpha), a molecule that is implicated in the immune response associated with psoriasis [13].By suppressing TNF-alpha, these drugs aid in illness management and inflammation relief [13].
Notwithstanding the accessibility of these biological drugs, rigorous evaluations that juxtapose their safety and efficacy profiles are necessary.These studies offer significant insights regarding the relative efficacy of various treatments and serve as a reference for clinical decision-making.Nevertheless, the number of systematic reviews and comparisons of these biological medicines for the treatment of psoriasis is insufficient.
As a result, by a systematic evaluation of the existing literature concerning the efficacy of several biological medicines for the treatment of psoriasis, this study seeks to fill this knowledge gap.The objective of this study is to conduct a thorough investigation of the relative efficacy of these drugs in alleviating psoriasis symptoms, decreasing inflammation, and increasing the quality of life for patients by synthesizing the existing evidence.The outcomes of this research results will augment the existing body of knowledge regarding the management of psoriasis and provide guidance to medical practitioners in the process of prescribing the most suitable biological therapy for their clients.

Study Design
A comprehensive review was undertaken to evaluate and compare the effectiveness of diverse biological medicines utilised in the management of psoriasis.In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, the review process was conducted with integrity and transparency.

Study Selection Criteria
The following inclusion criteria were applied to identify eligible studies.
Participants: Studies involving patients diagnosed with psoriasis, including both plaque psoriasis.
Comparator: Studies comparing the efficacy of different biological medications or comparing biological medications with placebo or other standard treatments.
Outcome measures: Studies reporting outcomes related to disease severity, such as Psoriasis Area and Severity Index (PASI) scores.

Study Design
Only RCTs were included in this review.

Study Selection Process
Five independent reviewers independently screened the titles and abstracts of the identified studies to assess their eligibility based on the inclusion criteria.Full-text articles of potentially eligible studies were obtained and assessed for final inclusion.Any discrepancies or disagreements between reviewers were resolved through discussion or consultation with a sixth or seventh reviewer if necessary.

Data Extraction
Data extraction was performed independently by five reviewers using a standardized data extraction form.
The following information was extracted from each included study: study characteristics (authors, year of publication, study design), participant characteristics (sample size, demographics), intervention details (type of biological medication, dosage, duration of treatment), comparator details, outcome measures, and results.

Results
In total, 475 studies were ascertained by the preliminary search of the database.After eliminating duplicate research, 358 distinct studies remained.After meticulous screening of titles and abstracts against the predefined inclusion criteria, 281 papers were deemed ineligible and thus excluded.For final inclusion, the whole texts of the remaining 77 studies were evaluated.Forty additional papers were removed during the full-text evaluation for a variety of reasons, including improper research design, irrelevant intervention, or insufficient outcome data.Finally, 37 studies were included in this systematic review since they satisfied all inclusion criteria.A detailed flowchart with the results of the literature review is shown in Figure 1.For the skin domain, results between 10 and 16 weeks were considered which is reported in all studies.The systematic review included a total of 37 RCTs focusing on the outcomes of the GRAPPA domain.These trials investigated various drugs and dosages and assessed multiple outcomes related to psoriasis.The review encompassed studies conducted between 2005 and 2021, with sample sizes ranging from 78 to 1,881 participants.The drugs evaluated in the trials included Risankizumab, secukinumab, guselkumab, adalimumab, certolizumab, etanercept, ustekinumab, brodalumab, ixekizumab, tildrakizumab, infliximab, methotrexate, briakinumab, golimumab, and ADA (adalimumab).The primary outcomes assessed in the included studies were categorized into several domains.These domains included measures of disease severity such as PASI (Psoriasis Area and Severity Index) scores, ACR (American College of Rheumatology) scores for arthritis, and assessments for dactylitis, enthesitis, and nail involvement (Table 1).Among the participants, 15,507 individuals had their sPSA (severity of psoriasis) categorized.Of these, 8,773 patients (56.5%) were classified as having severe psoriasis (category 3), 6,671 patients (43.0%) were categorized as having very severe psoriasis (category 4 or above), and 63 patients (0.5%) had milder cases of psoriasis (below category 3).
The study also investigated the use of different medications for psoriasis treatment.The sample sizes ranged from 277 patients for briakinumab to 3,709 patients for secukinumab.The mean ages were generally similar across medications, ranging from 41.8 years for methotrexate to 48.65 years for Risankizumab.The percentage of male patients was also comparable, varying from 57.3% for infliximab to 75.7% for guselkumab.The number of studies analyzed per medication ranged from one trial for tildrakizumab, golimumab, and briakinumab to eight studies for etanercept and secukinumab.Placebo arms accounted for the largest pooled sample size of 5,542 patients across 27 studies (Table 2).The data have been represented as the name of the drug used, sample size, age (Year), gender (Male), average duration of plaque psoriasis (Year), sPGA category represents the score of psoriasis based on Static physician global assessment score which ranges from 0 (No signs of plaque psoriasis) to 4 (Dark, red erythematous psoriatic plaques), next to each score is the number of participants in the study and their percentage from the overall participants in that particular study, last column shows the percentage of the average of body area involved.

Discussion
From among the several drugs that were evaluated, guselkumab consistently exhibited the most notable rates of improvement across all three PASI categories: 89.63%, 72.7%, and 48.47% for PASI75, PASI90, and PASI100, respectively.Consistent with prior research, the effectiveness of Guselkumab in the treatment of psoriasis certifies its status as a very successful therapeutic alternative [53][54][55].Ixekizumab had noteworthy effectiveness as well, as seen by improvement rates of 81.33%, 71.53%, and 37.83%, respectively, on the PASI75, PASI90, and PASI100, respectively.The findings of this study provide further support for the notion that ixekizumab is an effective treatment for psoriasis [56].
Both briakinumab and Risankizumab exhibited significant efficacy, as evidenced by the considerable rates of improvement observed in the PASI scores.Briakinumab demonstrated PASI scores of 34.62%, 63.14%, and 66.94%, whereas Risankizumab demonstrated PASI75, PASI90, and PASI100 scores of 84.5%, 66.83%, and 34.8%, respectively.The results underscore the efficacy of these pharmaceuticals in mitigating the symptoms associated with psoriasis.
Adalimumab, certolizumab, secukinumab, ustekinumab, and methotrexate were among the additional drugs that exhibited a modest degree of effectiveness in ameliorating symptoms associated with psoriasis.The observed variations in improvement rates among various drugs underscore the significance of taking into account the unique qualities and preferences of each patient when determining the most suitable course of treatment.It is noteworthy that although the improvement rates of these drugs may be comparatively lower than those of ixekizumab and guselkumab, they nonetheless provide substantial advantages in the management of psoriasis.
Conversely, the effectiveness of etanercept, golimumab (at a dosage of 50 mg), and TIL 100 mg was comparatively diminished in comparison to the aforementioned drugs.Etanercept induced the following percentage improvements in PASI75, PASI90, and PASI100: 43.24%, 17%, and 4.48%, respectively.The administration of 50 mg of golimumab resulted in 40.3% and 20.8% improvement rates for PASI75 and PASI90, respectively.Similarly, 100 mg of TIL produced improvement rates of 62.5%, 36.9%, and 13.15% for PASI75, PASI90, and PASI100, respectively.Patients whose responses to these drugs are inadequate may benefit more from alternate treatment modalities, according to these results.
Brodalumab demonstrated a significantly higher level of efficacy compared to secukinumab, ustekinumab, and etanercept, as evidenced by four 52-week RCTs.Similarly, secukinumab demonstrated more efficacy than ustekinumab, and both agents beat etanercept.The results obtained from thirteen supplementary trials and four additional therapeutic interventions (ixekizumab, apremilast, infliximab, and brodalumab) demonstrated that brodalumab exhibited the highest efficacy, followed by ustekinumab, infliximab, and ixekizumab.It was expected that etanercept would have the least lasting effect.At week 52, brodalumab was associated with a higher likelihood of prolonged PASI response, including complete clearance, in comparison to comparable medications.Furthermore, Sawyer et al. [65] did a network meta-analysis comprising 34,816 patients and 77 studies.The effectiveness of brodalumab, ixekizumab, secukinumab, guselkumab, and Risankizumab in the treatment of plaque psoriasis was shown to be superior to that of ustekinumab, tildrakizumab, all TNF-α inhibitors, non-biologic systemic medicines, as demonstrated by the researchers.Furthermore, it was observed that brodalumab, ixekizumab, and Risankizumab exhibited greater efficacy than secukinumab, however not by a substantial margin compared to guselkumab.In terms of PASI 90 and PASI 100 response, brodalumab, ixekizumab, guselkumab, and Risankizumab shown the most substantial improvements.According to a meta-analysis of 140 studies conducted by Shidian et al. [66], the percentage of patients attained by ixekizumab, secukinumab, bimekizumab, brodalumab, Risankizumab, and guselkumab with PASI 90 demonstrated that these agents were more effective than ustekinumab, adalimumab, certolizumab, and etanercept.Furthermore, adalimumab and ustekinumab had a higher degree of efficacy compared to certolizumab and etanercept.A comparison between the biological drugs and the placebo group provides more evidence of the biological therapies' better efficacy.The improvement rates of all biological drugs assessed on the PASI were found to be significantly greater in comparison to the placebo group.This underscores the significance of regarding these drugs as the benchmark for the management of psoriasis.
An optimal treatment regimen for a patient with psoriasis should consist of a solitary medication that exhibits efficacy across all indications.The study's exhaustive literature review offers significant insights into the effectiveness of several biological drugs in the treatment of psoriasis.Consistent with other investigations, the results validate the concept that briakinumab, ixekizumab, guselkumab, and ixekizumab are exceedingly efficacious therapeutic alternatives.Furthermore, methotrexate, adalimumab, certolizumab, secukinumab, and ustekinumab exhibit a moderate degree of efficacy in the management of symptoms associated with psoriasis.
By giving a complete review of the efficacy of various drugs, the results of this study contribute to the current body of knowledge on psoriasis treatment.However, a few limitations should be taken into account.
The study initially utilized data obtained from randomised controlled trials, which might not comprehensively represent treatment outcomes in the real world.A more positive response to treatment may be observed in the controlled trial setting as opposed to ordinary clinical practice.

Conclusions
The systematic review assessed the performance of several biological drugs in the treatment of psoriasis offers significant insights into the treatment's success.Adalimumab, certolizumab, secukinumab, ustekinumab, and methotrexate had moderate efficacy, whereas guselkumab, ixekizumab, Risankizumab, and briakinumab appeared as exceptionally successful alternatives.Clinicians can utilize these findings as a guide for determining which treatment is most suitable for specific patients.When making treatment options, it is essential to evaluate patient characteristics, treatment objectives, and potential adverse effects.Additional investigation into the long-term effects of various drugs and comparative analyses of their efficacy is necessary in order to advance our knowledge of psoriasis care.

Additional Information
Author Contributions

FIGURE 1 :
FIGURE 1: The PRISMA figure showing the steps to choose the studies for systematic review PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

TABLE 1 : RCT included in the systematic review focusing on the outcomes of GRAPPA domain
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, PASI: Psoriasis Area and Severity Index Score, ACR: American College of Rheumatology score for arthritis.The data have been represented as a year of publication, number of participants (N), name of the drug used, dosage of the used drug (mg) and outcomes based on Psoriasis Area and Severity Index Score (PASI).
RCT: Randomized Controlled Trial, GRAPPA:(19,929 individuals, accounting for 66.37% of the total sample).The mean age of the participants was 45.76 years, with a standard deviation of 2.10.The age range varied from 40.1 to 53.3 years.The average duration of plaque psoriasis among the participants was 16.47 years, with a standard deviation of 4.04.The minimum duration reported was 2.8 years, while the maximum duration reached 21 years.The body surface area affected by psoriasis had a mean value of 26.87%, with a standard deviation of 5.06.The range for body surface area varied from 12% to 41.6%.

TABLE 2 : General characteristics of the population and treatment
sPGA: Static Physicians Global Assessment, N: Number of participants, N%: Percentage of the participants from the total participants in the study, NA: Not Available.