Browsing by Subject "Efficacy"

Now showing 1 - 4 of 4
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    Open Access
    A retrospective study of patients with biologics treatment at Groote Schuur and Red Cross Children's War Memorial Hospitals
    (2020) Ahmed, Mohammed Awad Eltoum; Hodkinson, Bridget; Gcelu, Ayanda
    Introduction. The high cost and concern of adverse events, particularly infections, limit the use of biologic disease-modifying anti-rheumatic (bDMARD) therapies. We undertook this retrospective study to document their use for immune-mediated diseases (IMDs) and explore the efficacy, safety, adherence and screening practices prior to initiating bDMARDs in a tertiary referral hospital. Methods. A folder review of all adult and paediatric patients treated for IMDs with bDMARDs at Groote Schuur and Red Cross Hospitals between January 2013 and December 2019. Clinico-demographic particulars, details of bDMARD therapy, and adverse events were collated. Changes in disease activity were measured by diseasespecific tools at 6, 12, 24-months and at the last available visit, and patient adherence to bDMARDs was explored by folder and pharmacy record review. Results. We studied 151 folders, with 182 bDMARDs uses (29 patients used more than 1 bDMARD). Patients were from rheumatology (n= 38: 13 rheumatoid arthritis; 10 spondyloarthritis, 5 Systemic Lupus Erythematosus (SLE) , 5 inflammatory myositis and 5 other conditions); gastroenterology (n=31; 26 Crohn`s and 5 Ulcerative Colitis), dermatology (n=9; psoriasis), neurology (n=4, ophthalmology (n= 25; 6 scleritis, 18 uveitis, 1 optic neuritis), and paediatrics (n= 45, 26 juvenile idiopathic arthritis , 12 SLE, 7 other conditions). The bDMARDs used were TNF inhibitors (112), rituximab (55), tocilizumab (10), anakinra (3), abatacept (1), and tofacitinib (1). The vast majority of patients had an excellent response and were in low disease activity or remission at their last available visit. Adverse events included severe infection (4), tuberculosis (TB) (2), mild infection (4), severe allergic reaction (3), mild skin reaction (14), elevated liver enzymes (2), and worsening interstitial lung disease ILD (1). bDMARD Therapy was discontinued in 18 patients, most commonly due to adverse reaction (9), lack of response (3), poor adherence (2), or remission (1). bDMARD Therapy was changed to alternative therapy in 29 patients, most commonly because of poor response (14), or adverse effects (9) or poor adherence (3). Poor adherence or patients lost to follow-up was noted in 18/182 (9.9%). Complete latent TB infection screening with chest x-ray and TB skin test was performed in only 55 (36.4 %) but INH prophylaxis was given to 51/88 (57.9%) of patients prescribed TNFi therapy. Hepatitis B screening performed in 93 (61.6 %) patients, but most patients (72.2 %) were not tested for Hepatitis B core ab. Hepatitis C screening was performed in 81 (53.6 %) patients. Only 88 (58.3%) patients had a recent HIV test. The majority (17.2%) received the influenza vaccine, but only 24 (15.8 %) received pneumococcal vaccination. Discussion and Conclusion. bDMARD therapy was an effective treatment, and the most common adverse effect was infection (7.2%), with 2 TB infections. Vaccination and screening for TB, viral hepatitis and HIV was suboptimal. Of concern, poor adherence to bDMARDs was frequently encountered.
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    Open Access
    A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study
    (BioMed Central Ltd, 2015) Denoeud-Ndam, Lise; Dicko, Alassane; Baudin, Elisabeth; Guindo, Ousmane; Grandesso, Francesco; Sagara, Issaka; Lasry, Estrella; Palma, Pedro; Parra, Angeles; Stepniewska, Kasia; Djimde, Abdoulaye; Barnes, Karen; Doumbo, Ogobara; Etard, Jean-Francois
    BACKGROUND:Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded.Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking.The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.METHODS/DESIGN:In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded.Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program.Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.DISCUSSION:This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.TRIAL REGISTRATION:ClinicalTrials.gov: NCT01958905
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    Open Access
    Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial
    (2019-06-24) Raman, Jaishree; Allen, Elizabeth; Workman, Lesley; Mabuza, Aaron; Swanepoel, Hendrik; Malatje, Gillian; Frean, John; Wiesner, Lubbe; Barnes, Karen I
    Abstract Background To reduce onward falciparum malaria transmission, the World Health Organization recommends adding single low-dose (SLD) primaquine to artemisinin-based combination treatment in low transmission areas. However, uptake of this recommendation has been relatively slow given concerns about whether individual risks justify potential community benefit. This study was undertaken to generate comprehensive local data on the risk–benefit profile of SLD primaquine deployment in a pre-elimination area in South Africa. Methods This randomized, controlled open-label trial investigated adding a single low primaquine dose on day 3 to standard artemether–lumefantrine treatment for uncomplicated falciparum malaria. Efficacy, safety and tolerability of artemether–lumefantrine and primaquine treatment were assessed on days 3, 7, 14, 28 and 42. Lumefantrine concentrations were assayed from dried blood spot samples collected on day 7. Results Of 217 patients screened, 166 were enrolled with 140 randomized on day 3, 70 to each study arm (primaquine and no primaquine). No gametocytes were detected by either microscopy or PCR in any of the follow-up samples collected after randomization on day 3, precluding assessment of primaquine efficacy. Prevalence of the CYP2D6*4, CYP2D6*10 and CYP2D6*17 mutant alleles was low with allelic frequencies of 0.02, 0.11 and 0.16, respectively; none had the CYP2D6*4/*4 variant associated with null activity. Among 172 RDT-positive patients G6PD-genotyped, 24 (14%) carried the G6PD deficient (A−) variant. Median haemoglobin concentrations were similar between treatment arms throughout follow-up. A third of participants had a haemoglobin drop > 2 g/dL; this was not associated with primaquine treatment but may be associated with G6PD genotype [52.9% (9/17) with A− genotype vs. 31% (36/116) with other genotypes (p = 0.075)]. Day 7 lumefantrine concentrations and the number and nature of adverse events were similar between study arms; only one serious adverse event occurred (renal impairment in the no primaquine arm). The artemether–lumefantrine PCR-corrected adequate clinical and parasitological response rate was 100%, with only one re-infection found among the 128 patients who completed 42-day follow-up. Conclusions Safety, tolerability, CYP2D6 and G6PD variant data from this study support the deployment of the WHO-recommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission. Trial registration Pan African Clinical Trial Registry, PACTR201611001859416. Registered 11 November 2016, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1859
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    Open Access
    Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
    (BioMed Central, 2018-04-19) Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M
    Background: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. Methods/design: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Discussion: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smearnegative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. Trial registration: International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.