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The Cochrane Database of Systematic... Jun 2023Hepatitis B virus (HBV)-human Immunodeficiency virus (HIV) co-infection promotes an aggressive disease course of HBV infection. In the only available non-Cochrane... (Review)
Review
BACKGROUND
Hepatitis B virus (HBV)-human Immunodeficiency virus (HIV) co-infection promotes an aggressive disease course of HBV infection. In the only available non-Cochrane systematic review on antiviral therapy during pregnancy for prevention of mother-to-child transmission of HBV, none of the women studied had HBV-HIV co-infection but were either HBV- or HIV-seropositive. Treatment of HBV alone may develop HIV-strains that are resistant to non-nucleoside reverse transcriptase inhibitors. Accordingly, co-treatment of the HIV infection is recommended.
OBJECTIVES
To evaluate the benefits and harms of tenofovir-based antiviral combination regimens versus placebo, tenofovir alone, or non-tenofovir-based antiviral regimen either alone or in combination with HBV for the prevention of mother-to-child transmission of HBV in HIV-positive pregnant women co-infected with HBV.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS (Bireme), Science Citation Index Expanded (Web of Science), and Conference Proceedings Citation Index-Science (Web of Science) on 30 January 2023. We manually searched the reference lists of included trials, searched on-line trial registries, and contacted experts in the field and pharmaceutical companies for any further potential trials.
SELECTION CRITERIA
We aimed to include randomised clinical trials comparing tenofovir-based antiviral combination regimens (anti-HIV regimen with lopinavir-ritonavir therapy, or any other antiviral therapy, and two drugs with activity against HBV, specifically, tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), plus lamivudine or emtricitabine) with placebo alone, or tenofovir alone, or non-tenofovir-based antiviral regimen (zidovudine, lamivudine, telbivudine, emtricitabine, entecavir, lopinavir-ritonavir, or any other antiviral therapy) either alone or in combination with at least two other antivirals.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes included all-cause infant mortality, proportion of infants with serious adverse events, proportion of infants with HBV mother-to-child transmission, all-cause maternal mortality, and proportion of mothers with serious adverse events. Secondary outcomes included proportion of infants with adverse events not considered serious, proportion of mothers with detectable HBV DNA (deoxyribonucleic acid) (before delivery), maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. We used RevMan Web to carry out analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CIs). We performed sensitivity analysis. We assessed risk of bias using predefined domains, assessed the certainty of the evidence using GRADE, controlled risk of random errors with Trial Sequential Analysis, and presented outcome results in a summary of findings table.
MAIN RESULTS
Five completed trials were included, of which four trials contributed data to one or more of the outcomes. They included a total of 533 participants randomised to tenofovir-based antiviral combination regimens (196 participants) versus control (337 participants). The control groups received non-tenofovir-based antiviral regimens either as zidovudine alone (three trials) or as a combination of zidovudine, lamivudine and lopinavir-ritonavir (five trials). None of the trials used placebo or tenofovir alone. All trials were at unclear risk of bias. Four trials used intention-to-treat analyses. In the remaining trial, two participants in the intervention group and two in the control group were lost to follow-up. However, the outcomes of these four participants were not described. Tenofovir-based antiviral combination regimen versus control We are very uncertain about the effect of a tenofovir-based antiviral combination regimen versus control on all-cause infant mortality (RR 2.24, 95% CI 0.72 to 6.96; participants = 132; trials = 1; very low-certainty evidence); proportion of infants with serious adverse events (RR 1.76, 95% CI 1.27 to 2.43; participants = 132; trials = 1; very low-certainty evidence), and proportion of mothers with serious adverse events (RR 0.90, 95% CI 0.62 to 1.32; participants = 262; trials = 2; very low-certainty evidence). No trial reported data on the proportion of infants with HBV mother-to-child transmission and all-cause maternal mortality. We are also very uncertain about the effect of tenofovir-based antiviral combination regimens versus control on the proportion of infants with adverse events not considered serious (RR 0.94, 95% CI 0.06 to 13.68; participants = 31; trials = 1; very low-certainty evidence), and proportion of mothers with detectable HBV DNA (before delivery) (RR 0.66, 95% CI 0.42 to 1.02; participants = 169; trials = 2; very low-certainty evidence). No trial reported data on maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. All trials received support from industry.
AUTHORS' CONCLUSIONS
We do not know what the effects of tenofovir-based antiviral combination regimens are on all-cause infant mortality, proportion of infants with serious adverse events and proportion of mothers with serious adverse events, proportion of infants with adverse events not considered serious, and proportion of mothers with detectable HBV DNA before delivery because the certainty of evidence was very low. Only one or two trials, with insufficient power, contributed data for analyses. We lack randomised clinical trials at low risk of systematic and random errors, and fully reporting all-cause infant mortality, serious adverse events and reporting on clinical and laboratory outcomes, such as infants with HBV mother-to-child transmission, all-cause maternal mortality, maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion before delivery and maternal adverse events not considered serious.
Topics: Female; Humans; Infant; Pregnancy; Antiviral Agents; Coinfection; DNA, Viral; Emtricitabine; Hepatitis B e Antigens; Hepatitis B virus; HIV; HIV Infections; HIV Seropositivity; Infectious Disease Transmission, Vertical; Lamivudine; Lopinavir; Pregnant Women; Ritonavir; Tenofovir; Zidovudine
PubMed: 37306558
DOI: 10.1002/14651858.CD013653.pub2 -
Virology Journal Jun 2023ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens.
METHODS
A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses.
RESULTS
We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease.
CONCLUSION
IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.
Topics: Adult; Humans; Zidovudine; Interferon-alpha; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Lymphoma
PubMed: 37287047
DOI: 10.1186/s12985-023-02077-0 -
Cancer Medicine Jul 2023Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)-positive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)-positive subtype. This meta-analysis aimed to objectively explore the efficacy and safety of TKIs.
METHODS
Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta-analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5.
RESULTS
Thirteen clinical trials involving 987 HER2-positive BCBM patients were analyzed. A trend of longer progression-free survival (PFS) was observed in the TKI-containing arm compared to the non-TKI-containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35-1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3-5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%-32%), neutropenia (11%, 95% CI: 5%-18%), hepatic toxicity (7%, 95% CI: 1%-16%), and sensory neuropathy (6%, 95% CI: 2%-12%).
CONCLUSION
TKIs therapy improved the survival outcomes of HER2-positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.
Topics: Humans; Female; Breast Neoplasms; Capecitabine; Tyrosine Kinase Inhibitors; Brain Neoplasms; Progression-Free Survival; Protein Kinase Inhibitors
PubMed: 37255389
DOI: 10.1002/cam4.6180 -
Reviews in Medical Virology Jul 2023WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.
WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.
Topics: Humans; Tenofovir; Emtricitabine; HIV Infections; Anti-HIV Agents; Creatinine; Pre-Exposure Prophylaxis
PubMed: 37198721
DOI: 10.1002/rmv.2460 -
Current Oncology (Toronto, Ont.) Mar 2023To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC)... (Meta-Analysis)
Meta-Analysis
To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001-September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator's choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.
Topics: Humans; Carboplatin; Carcinoma, Transitional Cell; Cisplatin; Deoxycytidine; Network Meta-Analysis; Urinary Bladder Neoplasms
PubMed: 37185390
DOI: 10.3390/curroncol30040277 -
HIV Medicine Jul 2023Prevention of HIV transmission is fundamental to ending the HIV epidemic. Pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine (TDF-FTC) is an established... (Review)
Review
BACKGROUND
Prevention of HIV transmission is fundamental to ending the HIV epidemic. Pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine (TDF-FTC) is an established HIV-prevention method; however, most PrEP services in Europe have been targeted at men who have sex with men (MSM). A survey in 2021 by Women Against Viruses in Europe (WAVE) showed considerable variation in PrEP access and guidance for women throughout Europe. WAVE therefore commissioned this systematic review to provide insight into PrEP provision and barriers to uptake for women in Europe.
METHODS
PubMed, Embase, and Scopus were searched for studies (January 2013-May 2021) that reported on actual (e.g., efficacy and safety) or hypothetical (e.g., awareness, barriers, PrEP impact models) use of oral PrEP involving women (including cis, transgender, pregnant, migrant, and breastfeeding women). Search terms included HIV, pre-exposure prophylaxis (specifically TDF-FTC), and women. Studies performed outside of the World Health Organization European region were excluded.
RESULTS
The search identified 4716 unique citations, and 45 peer-reviewed articles (44 studies) were included. The majority of these studies (34/44 [77%]) included recipients or potential recipients of PrEP, representing 4699 women (243 transgender women). However, few studies were women focused (4/34 [12%]) or took place outside of Western Europe (3/34 [9%]). Across the three clinical studies that reported women-specific outcomes (60 transgender women, 13 pregnant, and 19 cis women), no breakthrough infections were recorded during the use of PrEP. Lack of awareness of PrEP, low self-estimation of HIV acquisition risk, concerns about stigma, lack of protection against other sexually transmitted infections, and PrEP interaction with hormones (for transgender women) were identified as barriers to use. The remaining studies examined healthcare professionals' perceptions of PrEP (9/44 [20%]), asked for public opinion (2/44 [5%]), or modelled the potential of PrEP for HIV prevention (1/44 [2%]).
CONCLUSIONS
This review revealed a notable lack of literature on PrEP for cis and transgender women in Europe. This is synonymous with a lack of PrEP provision for women in this region. Barriers to PrEP uptake are complex and rooted in institutional and societal stigma, which must be addressed at policy level. HIV prevention with PrEP is not 'one size fits all' and requires a nuanced gender-responsive approach. Further research into the use of PrEP in cis, pregnant, breastfeeding, and transgender women is essential if we are to stop HIV transmission by 2030.
Topics: Male; Pregnancy; Humans; Female; Homosexuality, Male; HIV Infections; Anti-HIV Agents; Sexual and Gender Minorities; Tenofovir; Emtricitabine; Pre-Exposure Prophylaxis
PubMed: 37088558
DOI: 10.1111/hiv.13458 -
Expert Review of Anti-infective Therapy Jun 2023Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living...
INTRODUCTION
Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens.
AREAS COVERED
A systematic review of the literature was carried out in the international databases PubMed/Medline, Web of Science (WoS), Scopus, Embase, and Cochrane Library from 2013 to June 2022. Ninety observational studies reporting data on treatment discontinuation due to drug-related adverse events and NPSs were identified.
EXPERT OPINION
Discontinuation rates due to NPSs increase with treatment time and, in light of the reviewed studies, are higher in PLHIV treated with DTG-based regimens compared with those treated with BIC/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF). This information could be useful for clinicians during treatment decision-making, reducing discontinuation rates and thereby promoting treatment success and durability. Additionally, the identification of potential risk factors in PLHIV prior to starting therapy could also help make the best therapy choices based on the characteristics of each individual.
Topics: Humans; HIV Infections; Integrase Inhibitors; Anti-HIV Agents; Emtricitabine; Treatment Outcome; Drug Combinations; Heterocyclic Compounds, 3-Ring; Amides; HIV Integrase Inhibitors
PubMed: 37074798
DOI: 10.1080/14787210.2023.2203914 -
Neurological Sciences : Official... Sep 2023Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision.
METHODS
The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS).
RESULTS
After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%).
CONCLUSION
Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.
Topics: Humans; Cladribine; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Clinical Trials as Topic; Observational Studies as Topic
PubMed: 37062787
DOI: 10.1007/s10072-023-06794-w -
AIDS Research and Therapy Mar 2023The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral...
An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor-based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1.
BACKGROUND
The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparison (ITC) was conducted to compare the durability of efficacy and long-term safety of DTG + 3TC vs second-generation, integrase strand transfer inhibitor (INSTI)-based, 3-drug, single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and DTG/abacavir/3TC (DTG/ABC/3TC) at Week 144 after treatment initiation.
METHODS
A systematic literature review identified 4 trials evaluating the treatment regimens of interest in ART-naive PWH (GEMINI-1, GEMINI-2, GS-US-380-1489, and GS-US-380-1490). Safety, efficacy, and tolerability results were compared using fixed-effects Bucher ITC methodology to calculate relative outcomes.
RESULTS
Rates of virologic suppression (HIV-1 RNA < 50 copies/mL, US Food and Drug Administration Snapshot analysis) and virologic failure (HIV-1 RNA ≥ 50 copies/mL) as well as mean change in CD4 + cell count were similar with DTG + 3TC, BIC/FTC/TAF, and DTG/ABC/3TC at Week 144. Serious adverse events occurred less frequently with DTG + 3TC compared with both BIC/FTC/TAF (odds ratio [OR], 0.51; 95% CI 0.29-0.87; P = 0.014) and DTG/ABC/3TC (OR, 0.38; 95% CI 0.19-0.75; P = 0.006). Discontinuations and overall adverse events were similar across all 3 regimens.
CONCLUSIONS
These results suggest that the 2-drug regimen DTG + 3TC offers comparable and durable efficacy with fewer serious adverse events vs BIC/FTC/TAF and DTG/ABC/3TC through 144 weeks of treatment in ART-naive PWH. These long-term comparative data support the therapeutic value of DTG + 3TC for PWH.
Topics: Humans; Lamivudine; HIV Infections; Anti-HIV Agents; HIV-1; Heterocyclic Compounds, 3-Ring; HIV Integrase Inhibitors; HIV Seropositivity; RNA; Tablets
PubMed: 36949442
DOI: 10.1186/s12981-023-00507-1 -
Multiple Sclerosis and Related Disorders Mar 2023The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.
METHODS
We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.
RESULTS
Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.
DISCUSSION
EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
Topics: Adult; Humans; Multiple Sclerosis; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Cladribine
PubMed: 36848839
DOI: 10.1016/j.msard.2023.104581