-
Anais Brasileiros de Dermatologia 2024Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of...
BACKGROUND
Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles.
METHODS
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results.
RESULTS
We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases.
STUDY LIMITATIONS
The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge.
CONCLUSION
Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.
Topics: Humans; Antibodies, Monoclonal; Dermatologists; Janus Kinase Inhibitors; Molecular Targeted Therapy; Skin Diseases
PubMed: 38521706
DOI: 10.1016/j.abd.2023.10.002 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
BMC Pediatrics Mar 2024Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a... (Meta-Analysis)
Meta-Analysis
Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.
Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Immunoglobulins, Intravenous; Glucocorticoids; Platelet Count; Methylprednisolone
PubMed: 38515126
DOI: 10.1186/s12887-024-04677-3 -
European Journal of Physical and... Mar 2024Over the last few decades, the use of neo/adjuvant therapies has significantly increased the number of breast cancer survivors who experience chemotherapy-induced...
INTRODUCTION
Over the last few decades, the use of neo/adjuvant therapies has significantly increased the number of breast cancer survivors who experience chemotherapy-induced peripheral neuropathy (CIPN). To date, few, low-efficacy, pharmacological remedies exist to manage this side effect. For this reason, alternative treatments are increasingly being investigated as possible strategies to prevent or promote faster recovery from CIPN. In this review we aimed to provide an overview of the literature evidence regarding all the non-pharmacological and rehabilitative interventions for patients affected by CIPN secondary to breast cancer care.
EVIDENCE ACQUISITION
A comprehensive literature search was conducted on PubMed, Scopus and Web of Science and included a total of 1895 patients (1528 with breast cancer) with a wide range of CIPN (motor, sensory and autonomic neuropathies) and chemotherapy treatments (e.g., Taxanes, Platins, Vinca alkaloids or monoclonal antibody drugs).
EVIDENCE SYNTHESIS
Of the initial 1108 hits, only 25 studies - describing different treatment modalities for peripheral neuropathies - were finally included in the qualitative synthesis. Most studies focused on acupuncture, physiotherapy, cryotherapy, and yoga.
CONCLUSIONS
There is still controversial evidence on conservative non-pharmacological interventions for the management of CIPN symptoms. We believe however that moderate exercise, as well as all types of stress reducing activities like sport, yoga and mindfulness, should be encouraged in cancer patients for their positive effect on global physical and psychological health. Further studies of higher methodological quality are needed to determine the best conservative approach to CIPN.
PubMed: 38502556
DOI: 10.23736/S1973-9087.24.08197-8 -
Frontiers in Immunology 2024There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate the effects of TNF-alpha inhibitors on lipid profiles (triglycerides, total cholesterol, low-density lipoprotein, or high-density lipoprotein) in patients with psoriasis.
METHODS
We searched PubMed, Embase, and Cochrane Library databases for articles published before October 17, 2023. Four TNF-alpha inhibitors (infliximab, etanercept, adalimumab, and certolizumab) were included in our study. (PROSPERO ID: CRD42023469703).
RESULTS
A total of twenty trials were included. Overall results revealed that TNF-alpha inhibitors elevated high-density lipoprotein levels in patients with psoriasis (WMD = 2.31; 95% CI: 0.96, 3.67; = 0.001), which was supported by the results of sensitivity analyses excluding the effect of lipid-lowering drugs. Subgroup analyses indicated that high-density lipoprotein levels were significantly increased in the less than or equal to 3 months group (WMD = 2.88; 95% CI: 1.37, 4.4; < 0.001), the etanercept group (WMD = 3.4; 95% CI = 1.71, 5.09, < 0.001), and the psoriasis group (WMD = 2.52; 95% CI = 0.57, 4.48, = 0.011). Triglyceride levels were significantly increased in the 3 to 6-month group (WMD = 4.98; 95% CI = 1.97, 7.99, = 0.001) and significantly decreased in the 6-month and older group (WMD = -19.84; 95% CI = -23.97, -15.7, < 0.001). Additionally, Triglyceride levels were significantly increased in the psoriasis group (WMD = 5.22; 95% CI = 2.23, 8.21, = 0.001).
CONCLUSION
Our results revealed that TNF-alpha inhibitors might temporarily increase high-density lipoprotein levels in patients with psoriasis. However, changes in triglycerides were not consistent among the different durations of treatment, with significant increases after 3 to 6 months of treatment. Future prospective trials with long-term follow-up contribute to confirming and extending our findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469703.
Topics: Humans; Etanercept; Tumor Necrosis Factor-alpha; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Psoriasis; Immunologic Factors; Triglycerides; Lipoproteins, HDL
PubMed: 38500874
DOI: 10.3389/fimmu.2024.1354593 -
Digestive Diseases and Sciences May 2024Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.
BACKGROUND
Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC).
AIMS
This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC.
METHODS
Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis.
RESULTS
Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks.
CONCLUSIONS
Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.
Topics: Humans; Infliximab; Antibodies, Monoclonal, Humanized; Injections, Subcutaneous; Gastrointestinal Agents; Colitis, Ulcerative; Crohn Disease; Administration, Intravenous; Treatment Outcome; Adult; Randomized Controlled Trials as Topic; Remission Induction; Network Meta-Analysis; Maintenance Chemotherapy
PubMed: 38499736
DOI: 10.1007/s10620-023-08252-1 -
The Lancet. Global Health May 2024WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector... (Meta-Analysis)
Meta-Analysis
Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa.
METHODS
For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986.
FINDINGS
Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission.
INTERPRETATION
Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission.
FUNDING
The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking.
TRANSLATIONS
For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Topics: Humans; Onchocerciasis; Ivermectin; Onchocerciasis, Ocular; Mass Drug Administration; Seroepidemiologic Studies; Africa South of the Sahara
PubMed: 38484745
DOI: 10.1016/S2214-109X(24)00043-3 -
Frontiers in Immunology 2024Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.
METHODS
PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.
RESULTS
Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% . 54%, < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% . 18%, < 0.01; grade ≥ 3: 43% . 15%, < 0.01) and lymphopenia (any grade: 37% . 8%, < 0.01; grade ≥ 3: 31% . 8%, = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% . 66%, = 0.84; grade ≥ 3: 1% . 1%, = 0.36) and infections (any grade: 47% . 49%, = 0.86; grade ≥ 3: 24% . 20%, = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% . 2%, < 0.01) and lower risks of fatigue (any grade: 14% . 30%, < 0.01) and pyrexia (any grade: 14% . 29%, < 0.01).
CONCLUSION
This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Prospective Studies; Neurotoxicity Syndromes; Neutropenia
PubMed: 38482019
DOI: 10.3389/fimmu.2024.1348955 -
Frontiers in Immunology 2024This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic... (Meta-Analysis)
Meta-Analysis
AIM
This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic syndrome (FRSDNS).
METHODS
We conducted systematic searches of PubMed, Embase, the Cochrane Library, and the Web of Science up to May 23, 2023. Outcome measures included relapses within 1 year, mean cumulative exposure to corticosteroids, patients with treatment failure at 1 year, relapse-free survival during 1 year, and adverse events. The quality of the included studies was evaluated using the modified Jadad scale, the Methodological Index for Non-Randomized Studies (MINORS), and the modified Newcastle-Ottawa Scale (NOS).
RESULTS
Rituximab was found to be the most likely (92.44%) to be associated with the fewest relapses within 1 year and was also most likely (99.99%) to result in the lowest mean cumulative exposure to corticosteroids. Rituximab had the highest likelihood (45.98%) of being associated with the smallest number of patients experiencing treatment failure at 1 year. CsA was most likely (57.93%) to achieve the highest relapse-free survival during 1 year, followed by tacrolimus (26.47%) and rituximab (30.48%). Rituximab showed no association with serious side effects and had comparable adverse effects to ofatumumab and tacrolimus.
CONCLUSION
Rituximab may be the most favorable immunosuppressive agent for treating pediatric FRSDNS. Nephrologists should consider this drug, along with their clinical experience, patient characteristics, and cost considerations, when choosing a treatment approach.
Topics: Child; Humans; Glucocorticoids; Immunosuppressive Agents; Nephrotic Syndrome; Network Meta-Analysis; Recurrence; Rituximab; Steroids; Tacrolimus
PubMed: 38464533
DOI: 10.3389/fimmu.2024.1310032 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810