The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy
Open accessAbstract
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (− 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60–80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP. Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the same phase III study, a higher incidence of rash was reported (69.2%); otherwise the safety profile was unchanged, as with clinical benefit.
“A higher incidence of rash was reported (69.2%); otherwise, the safety profile was unchanged, as with clinical benefit.”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [250]
In the same phase III study, a significant decrease was observed in PVL, CSF CXCL10/neopterin.
“However, a significant decrease was observed in PVL, CSF CXCL10/neopterin, the significance of which is discussed in Section 3.4.”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [250]
In a multicentre randomised phase III study of mogamulizumab, at the end of the double-blinded period, no significant difference was observed in the primary (OMDS) or secondary endpoints assessing motor function (10 WT).
“At the end of the double-blinded period, no significant difference was observed in the primary (OMDS) or secondary endpoints assessing motor function (10 WT).”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [250]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Yamano, Y., Araya, N., Sato, T., Utsunomiya, A., Azakami, K., Hasegawa, D., Izumi, T., Fujita, H., Aratani, S., Yagishita, N., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006517 · Cited by 140
Self-citationTsutsumi, S., Sato, T., Yagishita, N., Yamauchi, J., Araya, N., Hasegawa, D., Nagasaka, M., Coler-Reilly, A. L. G., Inoue, E., Takata, A., et al. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1212-4 · Cited by 33
Self-citation
Flagged first, then by citations
Research works printed but not linked: 27
- Gessain A, Cassar O (2012) Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol 3:388. https://doi.org/10.3389/fmicb.2012.00388 · DOI · Paper page
- Bangham CRM, Araujo A, Yamano Y et al (2015) HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat Rev Dis Primers 1:15012. https://doi.org/10.1038/nrdp.2015.12 · DOI
- Osame M, Usuku K, Izumo S et al (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–1032. https://doi.org/10.1016/s0140-6736(86)91298-5 · DOI
- Nakagawa M, Izumo S, Ijichi S et al (1995) HTLV-I-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J Neurovirol 1:50–61. https://doi.org/10.3109/13550289509111010 · DOI
- Olindo S, Cabre P, Lézin A et al (2006) Natural history of human T-lymphotropic virus 1-associated myelopathy: a 14-year follow-up study. Arch Neurol 63:1560–1566. https://doi.org/10.1001/archneur.63.11.1560 · DOI
- Martin F, Fedina A, Youshya S et al (2010) A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK. J Neurol Neurosurg Psychiatry 81:1336–1340. https://doi.org/10.1136/jnnp.2009.191239 · DOI · Paper page
- Yamano Y, Sato T (2012) Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis. Front Microbiol 3:389. https://doi.org/10.3389/fmicb.2012.00389 · DOI
- Coler-Reilly ALG, Yagishita N, Suzuki H et al (2016) Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net). Orphanet J Rare Dis 11:69. https://doi.org/10.1186/s13023-016-0451-x · DOI
- Satake M, Yamaguchi K, Tadokoro K (2012) Current prevalence of HTLV-1 in Japan as determined by screening of blood donors. J Med Virol 84:327–335. https://doi.org/10.1002/jmv.23181 · DOI
- Kaplan JE, Osame M, Kubota H et al (1990) The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J Acquir Immune Defic Syndr (1988) 3:1096–1101
- Sato T, Yagishita N, Tamaki K et al (2018) Proposal of classification criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis disease activity. Front Microbiol 9:1651. https://doi.org/10.3389/fmicb.2018.01651 · DOI
- Ishida T, Joh T, Uike N et al (2012) Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30:837–842. https://doi.org/10.1200/JCO.2011.37.3472 · DOI · Paper page
- Kasamon YL, Chen H, de Claro RA et al (2019) FDA approval summary: mogamulizumab-kpkc for mycosis fungoides and Sézary syndrome. Clin Cancer Res 25:7275–7280. https://doi.org/10.1158/1078-0432.CCR-19-2030 · DOI
- Hieshima K, Nagakubo D, Nakayama T et al (2008) Tax-inducible production of CC chemokine ligand 22 by human T cell leukemia virus type 1 (HTLV-1)-infected T cells promotes preferential transmission of HTLV-1 to CCR4-expressing CD4+ T cells. J Immunol 180:931–939. https://doi.org/10.4049/jimmunol.180.2.931 · DOI
- Araya N, Sato T, Ando H et al (2014) HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells. J Clin Investig 124:3431–3442. https://doi.org/10.1172/jci75250 · DOI
- Sato T, Coler-Reilly ALG, Yagishita N et al (2018) Mogamulizumab (anti-CCR4) in HTLV-1-associated myelopathy. N Engl J Med 378:529–538. https://doi.org/10.1056/NEJMoa1704827 · DOI · Paper page
- Sato T, Yamauchi J, Yagishita N et al (2023) Long-term safety and efficacy of mogamulizumab (anti-CCR4) for treating virus-associated myelopathy. Brain 146:3181–3191. https://doi.org/10.1093/brain/awad139 · DOI
- Izumo S, Goto I, Itoyama Y et al (1996) Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial. Neurology 46:1016–1021. https://doi.org/10.1212/wnl.46.4.1016 · DOI · Paper page
- Nomoto M, Utatsu Y, Soejima Y et al (1991) Neopterin in cerebrospinal fluid: a useful marker for diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis. Neurology 41:457. https://doi.org/10.1212/wnl.41.3.457 · DOI
- Nagai M, Usuku K, Matsumoto W et al (1998) Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol 4:586–593. https://doi.org/10.3109/13550289809114225 · DOI · Paper page
- Ando H, Sato T, Tomaru U et al (2013) Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy. Brain 136:2876–2887. https://doi.org/10.1093/brain/awt183 · DOI
- Sato T, Coler-Reilly A, Utsunomiya A et al (2013) CSF CXCL10, CXCL9, and neopterin as candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis 7:e2479. https://doi.org/10.1371/journal.pntd.0002479 · DOI
- Tamaki K, Sato T, Tsugawa J et al (2019) Cerebrospinal fluid CXCL10 as a candidate surrogate marker for HTLV-1-associated myelopathy/tropical spastic paraparesis. Front Microbiol 10:2110. https://doi.org/10.3389/fmicb.2019.02110 · DOI · Paper page
- Yamauchi J, Sato T, Yagishita N et al (2020) Use of cerebrospinal fluid CXCL10 and neopterin as biomarkers in HTLV-1-associated myelopathy/tropical spastic paraparesis treated with steroids. J Neurol Neurosurg Psychiatry 91:321–323. https://doi.org/10.1136/jnnp-2019-321955 · DOI
- Yamauchi J, Araya N, Yagishita N et al (2021) An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers. Pharmacol Ther 218:107669. https://doi.org/10.1016/j.pharmthera.2020.107669 · DOI
- Croda MG, de Oliveira AC, Vergara MP, Bonasser F, Smid J, Duarte AJ, Casseb J (2008) Corticosteroid therapy in TSP/HAM patients: the results from a 10 years open cohort. J Neurol Sci 269:133–137. https://doi.org/10.1016/j.jns.2008.01.004 · DOI · Paper page
- Coler-Reilly ALG, Sato T, Matsuzaki T et al (2017) Effectiveness of daily prednisolone to slow progression of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis: a multicenter retrospective cohort study. Neurotherapeutics 14:1084–1094. https://doi.org/10.1007/s13311-017-0533-z · DOI · Paper page
Cited by
Sorted by citations
Current State of Therapeutics for HTLV-1
Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22
“…Topical or systemic corticosteroids and mydriatics [263] HTLV-1-associated Sjögren’s Syndrome Artificial lubricants such as saliva/tears replacement solutions coupled with systemic pharmacotherapy with pilocarpine hydrochloride [264] HTLV-1-associated Hashimoto’s thyroiditis and Graves’ disease”
Background
Metadata
- Authors
- Sato, T., Nagai, M., Watanabe, O., Misu, T., Takenouchi, N., Ohkubo, R., Ishihara, S., Tsuboi, Y., Katsuno, M., Nakagawa, M., Matsushita, T., Aso, Y., Matsuura, E., Tokashiki, T., Mukaino, A., Adachi, H., Nakanishi, K., Yamaguchi, Y., Yamaguchi, S., & Yamano, Y.
- Affiliations
- St. Marianna University School of Medicine (JP)
- Ehime University Hospital (JP)
- Kagoshima City Hospital (JP)
- Tohoku University Hospital (JP)
- Kansai Medical University (JP)
- Fujimoto General Hospital (JP)
- University of the Ryukyus (JP)
- Fukuoka University (JP)
- Nagoya University (JP)
- Kyoto Prefectural University of Medicine (JP)
- Kyushu University (JP)
- Oita Prefectural Hospital (JP)
- Kagoshima University (JP)
- National Hospital Organization (JP)
- Kumamoto University Hospital (JP)
- University of Occupational and Environmental Health Japan (JP)
- Kyowa Kirin (Japan) (JP)
- Corresponding author
- Yamano, Yoshihisa
- ORCID
- Venue
- Journal of Neurology
- Published
- 2024-03-02
- Volume
- 271
- Issue
- 6
- Pages
- 3471-3485
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- PMC
- PMC11136778
- OpenAlex
- W4392348275
- Cited by
- 21
- References
- 2
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 4
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Kyowa Kirin
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Keywords
- mogamulizumab, HAM/TSP, tropical spastic paraparesis, HTLV-1 proviral load, neopterin, CXCL10, cerebrospinal fluid biomarkers, motor impairment, rash, disease progression
- MeSH terms
- Adult, Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Human T-lymphotropic virus 1, Paraparesis, Tropical Spastic, Treatment Outcome, Viral Load, Neopterin, Chemokine CXCL10, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
