-
1.
PML-RARA transcript levels at the end of induction therapy are associated with prognosis in non-high-risk acute promyelocytic leukaemia with all-trans retinoic acid plus arsenic in front-line therapy: long-term follow-up of a single-centre cohort study.
Tang, FF, Lu, SY, Zhao, XS, Qin, YZ, Liu, XH, Jia, JS, Wang, J, Gong, LZ, Jiang, Q, Zhao, T, et al
British journal of haematology. 2021;(5):722-730
Abstract
Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.
-
2.
All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial.
Huang, QS, Liu, Y, Wang, JB, Peng, J, Hou, M, Liu, H, Feng, R, Wang, JW, Xu, LP, Wang, Y, et al
The Lancet. Haematology. 2021;(10):e688-e699
Abstract
BACKGROUND High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.
-
3.
Oral Tranexemic Acid With Triple Combination Cream (Flucinolone+Hydroquinone+Tretinoin) Versus Triple Combination Cream Alone In Treatment Of Melasma.
Basit, A, Rahman, A, Uddin, R
Journal of Ayub Medical College, Abbottabad : JAMC. 2021;(2):293-298
Abstract
BACKGROUND Melasma is an acquired cutaneous disorder characterized by hyperpigmentation of the face predominantly affecting the areas exposed to direct sun light. The triple combination cream, i.e., a mid-potency corticosteroid (Fluocinolone acetonide 0.01%), a retinoid (Tretinoin 0.05%), and Hydroquinone 4% is one of the widely used topical medicament for melasma treatment world over. Tranexamic acid is another agent found to be effective in melasma treatment when used topically, intra-lesionally or orally. This study has been conducted to compare mean decrease in Melasma Area Severity Index (MASI) score when tranexamic acid is combined with triple combination cream versus triple combination cream alone for melasma treatment. METHODS A randomized controlled trial was conducted in a tertiary care hospital of Pakistan. Sixty-three patients of melasma who met the inclusion criteria and gave written informed consent for the study were enrolled. These patients were randomly divided into 2 treatment groups. Group A was given triple combination cream and oral tranxemic acid while Group B was given triple combination cream for duration of 8 weeks. Severity of melasma was assessed by MASI, which was calculated at baseline and at the end of week 8. Mean decrease in MASI score was calculated in both groups and statistically analysed employing SPSS 20. RESULTS Sixty patients, 30 in both groups, completed the study. Study participants were predominantly female (81.67%), with mean age of 30.46±6.24 years in group A while 31.90±4.53 in group B. No statistically significant difference was noted in both treatment groups for mean decrease in the MASI score (6.4933±4.38358 in group A compared to 5.7833±5.04251 in the group B; p-value 0.56). CONCLUSIONS The addition of oral tranexamic acid did not contribute significantly in decrease in MASI score when used in combination with topical triple regimen. It may have a role as an adjuvant to topical triple combination cream.
-
4.
Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.
Wang, YJ, Lin, ET, Chen, YT, Chiu, PC, Lin, BS, Chiang, HM, Huang, YH, Wang, KY, Lin, HY, Chang, TM, et al
Journal of the European Academy of Dermatology and Venereology : JEADV. 2020;(3):624-632
Abstract
BACKGROUND Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC: fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals) or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12 and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS Nine, 11 and 6 participants in groups A1, A2 and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2 and B, the improvement rates at week 20 were 53%, 38% and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores and brown spots after 3 laser sessions (P < 0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles and pores; however, only red areas were significantly different (P < 0.001). All side-effects in the 3 groups were transient and gradually subsided after 1-3 months. CONCLUSION Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions.
-
5.
Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial.
Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, et al
Leukemia. 2020;(3):914-918
-
6.
DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo.
Campuzano-García, AE, Torres-Alvarez, B, Hernández-Blanco, D, Fuentes-Ahumada, C, Cortés-García, JD, Castanedo-Cázares, JP
BioMed research international. 2019;:9068314
Abstract
BACKGROUND Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. OBJECTIVE To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. METHODS Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. RESULTS The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. CONCLUSIONS We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.
-
7.
Efficacy and Tolerability of a Novel Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate or Severe Acne Vulgaris in Adult Females.
Harper, JC, Baldwin, H, Stein Gold, L, Guenin, E
Journal of drugs in dermatology : JDD. 2019;(11):1147-1154
Abstract
Background: A novel tretinoin 0.05% lotion formulation has been shown to be efficacious and well-tolerated, and especially effective in adult female acne patients. While it is perhaps counter-intuitive that patients with more severe disease would show clinically significant improvement with topical monotherapy, topical retinoids have been shown to offer realistic treatment options in these patients. Objective: To evaluate the safety and efficacy of once-daily tretinoin 0.05% lotion in adult females with moderate or severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Adult females (>=18 years of age) with moderate (N=551) and severe (N=55) acne were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions, treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear) and quality of life (QoL) using the validated Acne-QoL questionnaire. Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, efficacy in adult females with moderate acne (EGSS=3) treated with tretinoin 0.05% lotion was significantly greater than that reported with vehicle. Mean percent reduction in inflammatory and noninflammatory lesion counts was 58.5% and 55.5% respectively compared with 50.3% and 39.8% with vehicle (P=0.039 and P<0.001). Treatment success was achieved by 25.4% of subjects by week 12, compared with 15.4% with vehicle (P=0.006). Tretinoin 0.05% lotion was numerically more effective in adult females with severe acne (EGSS=4). Mean percent reduction in inflammatory and noninflammatory lesion counts was 59.0% and 58.8% respectively (compared with 53.5% and 45.5% with vehicle), and treatment success was achieved by 17.9% of subjects (compared with 4.5% with vehicle), with 46.6% of subjects achieving at least a 2-grade improvement in EGSS by week 12. Quality of life improvements with tretinoin 0.05% lotion were significant compared with vehicle in adult females with moderate acne (except role-social), but not in severe acne (probably due to the group size). The majority of AEs were mild and transient; more frequently reported in the moderate acne population where application site pain (2.9%), and application site dryness (5.0%) were the most common, compared with one report (4.5%) of application site pain and dryness in the severe acne population. Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Limitations: The number of severe subjects enrolled in the studies was considerably less than the number of subjects with moderate acne, and the studies were not powered to demonstrate a difference in efficacy based on acne severity. Conclusions: Tretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in adult females with moderate acne, with notable improvements in treating adult females with severe acne. It was well-tolerated, and all treatment-related AEs were mild or moderate. J Drugs Dermatol. 2019;18(11):1147-1154.
-
8.
Oral arsenic plus retinoic acid versus intravenous arsenic plus retinoic acid for non-high-risk acute promyelocytic leukaemia: a non-inferiority, randomised phase 3 trial.
Zhu, HH, Wu, DP, Du, X, Zhang, X, Liu, L, Ma, J, Shao, ZH, Ren, HY, Hu, JD, Xu, KL, et al
The Lancet. Oncology. 2018;(7):871-879
Abstract
BACKGROUND Intravenous arsenic trioxide plus all-trans retinoic acid (ATRA) without chemotherapy is the standard of care for non-high-risk acute promyelocytic leukaemia (white blood cell count ≤10 × 109 per L), resulting in cure in more than 95% of cases. However, a pilot study of treatment with oral arsenic realgar-Indigo naturalis formula (RIF) plus ATRA without chemotherapy, which has a more convenient route of administration than the standard intravenous regimen, showed high efficacy. In this study, we compare an oral RIF plus ATRA treatment regimen with the standard intravenous arsenic trioxide plus ATRA treatment regimen in patients with non-high-risk acute promyelocytic leukaemia. METHODS We did a multicentre, non-inferiority, open-label, randomised, controlled phase 3 trial at 14 centres in China. Patients aged 18-70 years with newly diagnosed (within 7 days) non-high-risk acute promyelocytic leukaemia, and a WHO performance status of 2 or less were eligible. Patients were randomly assigned (2:1) to receive treatment with RIF-ATRA or arsenic trioxide-ATRA as the induction and consolidation therapy. Randomisation was done centrally with permuted blocks and stratification according to trial centre and was implemented through an interactive web response system. RIF (60 mg/kg bodyweight daily in an oral divided dose) or arsenic trioxide (0·15 mg/kg daily in an intravenous dose) and ATRA (25 mg/m2 daily in an oral divided dose) were used until complete remission was achieved. The home-based consolidation therapy was RIF (60 mg/kg daily in an oral divided dose) or intravenous arsenic trioxide (0·15 mg/kg daily in an intravenous dose) in a 4-week on 4-week off regimen for four cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week on 2-week off regimen for seven cycles. Patients and treating physicians were not masked to treatment allocation. The primary outcome was event-free survival at 2 years. A non-inferiority margin of -10% was used to assess non-inferiority. Primary analyses were done in a modified intention-to-treat population of all patients who received at least one dose of their assigned treatment and the per-protocol population. This study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13004054), and the trial is complete. FINDINGS Between Feb 13, 2014, and Aug 31, 2015, 109 patients were enrolled and assigned to RIF-ATRA (n=72) or arsenic trioxide-ATRA (n=37). Three patients in the RIF-ATRA and one in the arsenic trioxide-ATRA did not receive their assigned treatment. After a median follow-up of 32 months (IQR 27-36), 67 (97%) of 69 patients in the RIF-ATRA group and 34 (94%) of 36 in the arsenic trioxide-ATRA group had achieved 2-year event-free survival in the modified intention-to-treat population. The percentage difference in event-free survival was 2·7% (95% CI, -5·8 to 11·1). The lower limit of the 95% CI for the difference in event-free survival was greater than the -10% non-inferiority margin, confirming non-inferiority (p=0·0017). Non-inferiority was also confirmed in the per-protocol population. During induction therapy, grade 3-4 hepatic toxic effects (ie, increased liver aspartate aminotransferase or alanine transaminase concentrations) were reported in six (9%) of 69 patients in the RIF-ATRA group versus five (14%) of 36 patients in the arsenic trioxide-ATRA group; grade 3-4 infection was reported in 15 (23%) of 64 versus 15 (42%) of 36 patients. Two patients in the arsenic trioxide-ATRA group died during induction therapy (one from haemorrhage and one from thrombocytopenia). INTERPRETATION Oral RIF plus ATRA is not inferior to intravenous arsenic trioxide plus ATRA for the treatment of patients with non-high-risk acute promyelocytic leukaemia. This study suggests that a completely oral, chemotherapy-free model might be an alternative to the standard intravenous treatment for patients with non-high-risk acute promyelocytic leukaemia. FUNDING Foundation for innovative research group of the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the National Key R&D Program of China, and the National Natural Science Foundation of China.
-
9.
A randomized, split-face, controlled, double-blind, single-centre clinical study: transient addition of a topical corticosteroid to a topical retinoid in patients with acne to reduce initial irritation.
Coman, GC, Holliday, AC, Mazloom, SE, Chavan, RN, Kolodney, MS
The British journal of dermatology. 2017;(2):567-569
-
10.
The preadolescent acne microbiome: A prospective, randomized, pilot study investigating characterization and effects of acne therapy.
Coughlin, CC, Swink, SM, Horwinski, J, Sfyroera, G, Bugayev, J, Grice, EA, Yan, AC
Pediatric dermatology. 2017;(6):661-664
Abstract
BACKGROUND/OBJECTIVES Acne, a common pediatric disease, tends to be more comedonal in preadolescents, whereas older individuals are more likely to have inflammatory lesions in addition to comedones. Thus the microbiome of preadolescents may be different. In this pilot study we aimed to characterize the preadolescent acne microbiome, compare the microbiome in preadolescents with and without acne, and investigate changes in the microbiome after topical treatment with benzoyl peroxide or a retinoid in a small cohort of preadolescents. METHODS Participants were 7-10 years of age with (intervention group) or without (control group) acne and were recruited during routine outpatient dermatology visits. Baseline questionnaires, physical examination, and pore strip application were performed for all participants. Intervention group participants were randomized to receive topical therapy with benzoyl peroxide 5% gel or cream or tretinoin 0.025% cream. Participants with acne were followed up 8-10 weeks later and pore strip application was repeated. RESULTS Preadolescents with acne were colonized with a greater diversity of cutaneous bacteria than controls and the most commonly identified bacterium was Streptococcus. The number of bacterial species and phylogenetic diversity decreased after treatment with benzoyl peroxide and tretinoin. CONCLUSION The predominant bacteria in microbiome studies of adult acne is Propionibacterium, whereas in this pediatric population we saw a lot of Streptococcus bacteria. After treatment, the microbiomes of intervention group participants more closely resembled those of control group participants.