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Frontiers in Pharmacology 2023Psoriasis vulgaris (PV) is a longstanding, inflammatory, immune-responsive skin condition. Chinese herbal medicine injections (CHMIs) have been utilized for treating PV...
Psoriasis vulgaris (PV) is a longstanding, inflammatory, immune-responsive skin condition. Chinese herbal medicine injections (CHMIs) have been utilized for treating PV in Asian countries. This study aims to conduct a thorough systematic review and meta-analysis to comprehensively appraise the efficacy of CHMIs in treating PV. Seven databases were searched for randomized controlled trials that evaluated the effect of CHMIs in treating PV, ranging from 2004 to June 2022. The meta-analysis was undertaken based on outcome measures, treatment options, and treatment durations using Review Manager 5.4. The primary outcome measure of this study was a 60% or higher reduction in the Psoriasis Area and Severity Index score (PASI 60). A descriptive analysis was performed for the assessment of adverse events. This systematic review incorporated 33 studies, comprising 3,059 participants. The main findings indicated significant differences based on the PASI 60 (RR = 1.30, 95% CI: 1.24 to 1.37, Z = 10.72, < 0.00001), PASI 30 (RR = 1.25, 95% CI: 1.13 to 1.38, Z = 4.48, < 0.00001), and PASI 20 (RR = 1.28, 95% CI: 1.13 to 1.45, Z = 3.82, = 0.0001) outcome measures. Evaluating the treatment options, CHMIs in combination with monotherapies like narrowband ultraviolet B (NB-UVB) and the acitretin capsule (AC) showed a greater reduction in PASI 60 (RR = 1.33, 95% CI: 1.25 to 1.43, Z = 8.32, < 0.00001). In terms of treatment duration, no significant difference was observed when the duration extended beyond 56 days. Furthermore, the results suggested that CHMIs might reduce the incidence of adverse events in the treatment of PV. This systematic review revealed preliminary clinical evidence supporting the use of CHMIs for treating PV, considering outcome measures, treatment options, and treatment durations. However, due to the low methodological quality and limited sample size of the included studies, there is an urgent need for high-quality, multi-center and larger-scale studies of CHMIs for PV to provide robust evidence for their clinical application. : [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326531], identifier [CRD42022326531].
PubMed: 37465524
DOI: 10.3389/fphar.2023.1148445 -
The Journal of Rheumatology Mar 2023Nail psoriasis is common, impairs fine motor finger functioning, affects cosmesis, and is associated with a lower quality of life. This review updates the previous Group...
OBJECTIVE
Nail psoriasis is common, impairs fine motor finger functioning, affects cosmesis, and is associated with a lower quality of life. This review updates the previous Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for nail psoriasis.
METHODS
This systematic literature review of the PubMed, MEDLINE, Embase, and Cochrane databases examined the updated evidence since the last GRAPPA nail psoriasis treatment recommendations published in 2014. Recommendations are based on preformed PICO (Patient/Population - Intervention - Comparison/Comparator - Outcome) questions formulated by an international group of dermatologists, rheumatologists, and patient panel members. Data from this literature review were evaluated in line with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
RESULTS
Overall, there is insufficient evidence to make any recommendation for the use of topical corticosteroids, topical calcipotriol, topical tazarotene, topical cyclosporine, dimethyl fumarates/fumaric acid esters, phototherapy, and alitretinoin. There is a low strength of evidence to support the use of calcipotriol and corticosteroid preparations, topical tacrolimus, oral cyclosporine, oral methotrexate, intralesional corticosteroids, pulsed dye laser, acitretin, Janus kinase inhibitors, and apremilast.
CONCLUSION
The highest strength of supporting evidence is for the recommendation of biologic agents including tumor necrosis factor inhibitors, and interleukin 12/23, 17, and 23 inhibitors.
Topics: Humans; Arthritis, Psoriatic; Quality of Life; Psoriasis; Nail Diseases; Adrenal Cortex Hormones; Cyclosporins
PubMed: 36319021
DOI: 10.3899/jrheum.220313 -
Frontiers in Pharmacology 2022Psoriasis represents the chronic, recurrent and inflammatory disorder. The Traditional Chinese Medicine Xiyanping injection (XYP) is extensively applied in China for...
Psoriasis represents the chronic, recurrent and inflammatory disorder. The Traditional Chinese Medicine Xiyanping injection (XYP) is extensively applied in China for treating diverse inflammatory disorders, such as bronchitis, viral pneumonia or upper respiratory tract infection. XYP may offer a potential treatment for psoriasis vulgaris (PV). This study focused on analyzing whether XYP combined with acitretin was effective and safe. The present meta-analysis was carried out in line with guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic review was registered in PROSPERO (CRD42022333273). Besides, relevant randomized controlled trials (RCTs) that compared XYP plus acitretin with acitretin alone for treating PV were searched from several databases from their inception till May 2022. In addition, this work utilized RevMan5.4 to conduct risk assessment as well as meta-analysis. This meta-analysis selected altogether 10 RCTs including 815 subjects. Upon quality assessment, the RCTs mainly had low or unclear risk. According to our meta-analysis results, relative to acitretin monotherapy, XYP plus acitretin increased the total clinical effective rate, as evidenced by Psoriasis area and severity index score (PASI)-20, PASI-30 and PASI-60 in patients with PV [risk ratio (RR) = 1.23 Z = 4.87, < 0.00001, 95% confidence interval (CI): 1.13-1.34; RR = 1.29, Z = 3.89, = 0.009, 95% CI: 1.07 to 1.55; and RR = 1.31, Z = 3.89, = 0.0001, 95% CI: 1.14-1.49]; the reduced levels of TNF-α, MCP-1 and RANTES, the alleviated side effects resulting from acitretin like itchiness (RR = 0.54, 95% CI: 0.4 to 0.74, = 3.94, < 0.0001), and the increased levels of aminotransferases and dyslipidemia (RR = 0.5, 95%CI = 0.29, 0.86, = 0.01; and RR = 0.41, 95% CI = 0.23, 0.75, = 0.004). As suggested in the present meta-analysis, XYP combined with acitretin effectively and safely treats PV. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022333273, identifier PROSPERO 2022 CRD42022333273.
PubMed: 36147319
DOI: 10.3389/fphar.2022.971715 -
Journal of Traditional Chinese Medicine... Aug 2022To evaluate the clinical efficacy and safety of external application of Chinese herbal medicine (ex-CHM) for psoriasis vulgaris (PV). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the clinical efficacy and safety of external application of Chinese herbal medicine (ex-CHM) for psoriasis vulgaris (PV).
METHODS
Different search portals, including the China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang, SinoMed, clinicaltrials, PubMed, Cochrane Library, and Cochrane Central Register of Controlled Trials, were searched for randomized controlled trials (RCTs) that compared the ex-CHM intervention with other treatment protocols for PV, with available data as of November 25, 2020. The Review Manager 5.3 software was used for analysis.
RESULTS
Nineteen RCTs involving 1988 participants were included, of which twelve RCTs qualified for the Meta-analysis. The results showed that the addition of CHM bath to narrow-band ultraviolet B (NB-UVB) had a higher response rate [RR = 1.29; 95% CI (1.19, 1.40); P < 0.000 01]; lower psoriasis area severity index (PASI) [MD = -3.15; 95% CI (-4.79, -1.52); P = 0.000 2)], adverse reactions rate [RR = 0.32; 95% CI (0.15, 0.66); P = 0.002], and recurrence rate [RR = 0.48; 95% CI (0.30, 0.79); P=0.004] than NB-UVB alone. The addition of CHM fumigation to NB-UVB also showed a higher response rate [RR = 1.29; 95% CI (1.11, 1.49); P = 0.000 7] and lower adverse reactions rate [RR = 0.44; 95% CI (0.24, 0.79); P=0.006]. In addition, CHM bath could reduce the adverse reactions induced by 308 nm excimer laser and improve patients' quality of life better than phototherapy. CHM fumigation could improve the efficacy of calcipotriol ointment and reduce the adverse reactions. CHM fumigation combined with external washing plus acitretin showed better results than using acitretin alone. No statistical difference was observed between CHM external washing and calcipotriol ointment or CHM ointment and retinoic acids.
CONCLUSIONS
Current evidence showed that CHM bath and fumigation appeared to be efficient and safe for PV treatment. However, no definite conclusion could be drawn due to the low quality of included studies and thus more well-designed studies are needed for further assessment.
Topics: Acitretin; Drugs, Chinese Herbal; Humans; Ointments; Psoriasis; Randomized Controlled Trials as Topic
PubMed: 35848965
DOI: 10.19852/j.cnki.jtcm.20220617.001 -
The Journal of Clinical and Aesthetic... Jun 2022Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly...
OBJECTIVE
Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis.
METHODS OF LITERATURE SEARCH
By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality.
RESULTS
Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases.
LIMITATIONS
Our results are limited by the lack of data from RCTs.
CONCLUSION
Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.
PubMed: 35784449
DOI: No ID Found -
Risk of Skin Cancer with Phototherapy in Moderate-to-Severe Psoriasis: An Updated Systematic Review.The Journal of Clinical and Aesthetic... Jun 2022Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to...
Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to conduct a systematic review of skin cancer risk for psoriasis patients treated with phototherapy. To achieve our goal, we searched Cochrane, PubMed, and Embase databases. We aimed to evaluate existing literature (from July 1, 2010, to December 31, 2020) on phototherapy for all Fitzpatrick skin phototypes (FSP) which includes 71 articles, and eight articles being categorized in this review. Five studies did not report an increased skin cancer risk with narrowband-ultraviolet blue (UVB) and unspecified UVB for FSP II through VI, with one study not reporting FSP. Three studies did report an increased risk of skin cancer with narrowband-UVB and broadband-UVB for FSP I-VI, with one study also not specifying skin phototypes or UVB phototherapy type. Additionally, a study with psoralen and ultraviolet A with and without narrowband-UVB demonstrated an increased risk of skin cancer in phototypes III and IV. The most commonly reported secondary outcomes with phototherapy were actinic keratosis (123) and solar lentigines (10). Numerous patients were also on additional therapies including methotrexate, acitretin, and biologics. Study limitations include publication bias due to limited number of studies published on this topic in the last ten years along with heterogeneity in reporting. The relationship between phototherapy, psoriasis, and cutaneous oncogenic risk remains contradictory. While phototherapy for psoriasis is an efficacious therapy, further studies are needed to understand the cutaneous oncogenic risk based on FSP to help clinicals tailor treatment recommendations based on skin phototypes.
PubMed: 35783563
DOI: No ID Found -
Therapeutic Advances in Chronic Disease 2022Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks...
BACKGROUND
Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks associated with different treatments remain largely unknown. In this meta-analysis, we examined the relative risk of HZ associated with systemic treatments for psoriatic disease.
METHODS
PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant English-language studies published up to April 2021. Data were extracted using a standardized data extraction form. Network meta-analyses (NMA) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We examined the differences in HZ risk (incidence rate ratio; IRR) between treatments using a random-effects model for direct pairwise comparisons and NMA. The surface under the cumulative ranking area was calculated to rank the HZ risk for each treatment condition.
RESULTS
This study analyzed 13 studies including 19 treatment arms involving a total of 443,104 patients with psoriatic disease. Corticosteroids (CS) [IRR, 2.56; 95% confidence interval (CI), 1.59-4.13], a Janus kinase inhibitor (JAKi; tofacitinib) (IRR, 2.34; 95% CI, 1.03-5.32), infliximab (IRR, 2.32; 95% CI, 1.27-4.21), conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) + CS (IRR, 2.26; 95% CI, 1.23-4.17), anti-tumor necrosis factor-α (anti-TNF-α) + csDMARDs and/or CS (IRR, 2.13; 95% CI, 1.38-3.31), csDMARDs (IRR, 1.62; 95% CI, 1.18-2.22), and anti-TNF-α except infliximab (IRR, 1.61; 95% CI, 1.13-2.30) were all associated with a significantly higher HZ risk compared to controls. CS treatment possessed the highest HZ risk, followed by infliximab and JAKi (tofacitinib). Phosphodiesterase-4 inhibitor, anti-interleukin-17, -23 or -12/23, phototherapy, and acitretin showed a risk similar to controls without significant differences.
CONCLUSION
The NMA demonstrated CS, infliximab, and JAKi (tofacitinib), and several combination treatments were associated with higher HZ risk in patients with psoriasis and psoriatic arthritis. Differences in HZ risk should be taken into consideration when considering optimal psoriasis treatment.
PubMed: 35519434
DOI: 10.1177/20406223221091188 -
Frontiers in Medicine 2021Psoriasis continues to have unmet needs in its management despite introduction of newer molecules. Monotherapy with these newer agents may not achieve therapeutic goals...
Psoriasis continues to have unmet needs in its management despite introduction of newer molecules. Monotherapy with these newer agents may not achieve therapeutic goals in all cases, hence necessitating their combinations with other molecules. Improved understanding of newer as well as conventional treatment modalities and experiences in their combinations hence necessitates therapeutic guidelines for their use in psoriasis. To review the combinations of treatments reported in literature and recommendations for their use based on best current evidence in literature. A literature review of MEDLINE database for studies evaluating combinations of newer therapies with conventional therapies in psoriasis was done. Newer therapies were identified as biologic disease modifying anti rheumatic drugs and other molecules such as apremilast while conventional therapies included methotrexate, cyclosporine, or retinoids, phototherapy and others. The therapeutic guidelines are proposed with the aim to provide evidenced based approach to combine newer and conventional agents in day-to-day psoriasis management. Combination of acitretin and narrow band ultraviolet B (NB-UVB)/Psoralen with ultraviolet A (PUVA) achieves faster clearance and allows reduction of dose of the latter. A variable outcome is reported of methotrexate with TNF-α inhibitors vs. TNF-α inhibitors alone, although addition of methotrexate appears to reduce immunogenicity of TNF-α inhibitors thereby preventing formation of anti-drug antibodies especially in case of infliximab. While combination of acitretin and PUVA is beneficial, combining TNF-α inhibitors and phototherapy too produces better and faster results but long term risks of Non Melanoma Skin Cancers (NMSCs) may preclude their use together. Combination of cyclosporine and phototherapy is not recommended due to greater chances of NMSCs. Adding phototherapy to Fumaric Acid Esters (FAEs) improves efficacy. Apremilast can be safely combined with available biologic agents in patients with plaque psoriasis or psoriatic arthritis not responding adequately to biologics alone. Hydroxyurea and acitretin may be used together increasing their efficacy and reducing doses of both and hence their adverse effects. Selected clinical scenarios shall benefit from combinations therapies, improving efficacy of both conventional and newer agents and at the same time helping reduce toxicity of higher dosages when used individually.
PubMed: 34490293
DOI: 10.3389/fmed.2021.696597 -
Dermatology Online Journal Jul 2021Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries...
Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.
Topics: Acitretin; Administration, Oral; Adult; Anti-Bacterial Agents; Clobetasol; Glucocorticoids; Granuloma, Pyogenic; Humans; Keratoderma, Palmoplantar; Keratolytic Agents; Male; Mupirocin; Nail Diseases
PubMed: 34391333
DOI: 10.5070/D327754369 -
The Cochrane Database of Systematic... Apr 2021Psoriasis 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
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 non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.
SEARCH METHODS
For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of systemic 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. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events.
DATA COLLECTION AND ANALYSIS
Several 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 PASI 90 score) and acceptability (the inverse of serious adverse events). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety).
MAIN RESULTS
We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (58%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding. Network meta-analysis at class level showed that all of the interventions (non-biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90. At class level, in 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 non-biological systemic agents. At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti-TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non-biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high-certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high-certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high-certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high-certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high-certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
AUTHORS' CONCLUSIONS
Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 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. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials directly comparing active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between non-biological systemic agents 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 participants, 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. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Chronic Disease; Cytokines; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Molecular Targeted Therapy; Network Meta-Analysis; Placebos; Psoriasis; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 33871055
DOI: 10.1002/14651858.CD011535.pub4