PO10-TU-39 Safety and tolerability of short-course oral treatment with cladribine tablets for relapsing-remitting multiple sclerosis (RRMS) in the 96-week, phase III, double-blind, placebo-controlled CLARITY study

Cook, S; Vermersch, P.; Comi, Giancarlo; Giovannoni, Gavin; Rammohan, Kottil; Rieckmann, Peter; Soelberg-Sorensen, Per; Chang, Pei‐Hung; Hamlett, A; Musch, B; Viglietta, Vissia; Greenberg, SJ

doi:10.1016/s0022-510x(09)70788-9

Cited by 9 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cladribine tablets have a safety and tolerability profile that has been established and shown to be consistent across several studies (Tables 4 and 5). In CLARITY and CLARITY Extension, approximately 90% of actively treated patients completed each study, and there were relatively few study discontinuations due to AEs [12,45,46]. Most AEs in each study were classed as mild or moderate, and most occurred at similar frequencies across treatment groups, with the exception of lymphopenia, which was higher in groups treated with cladribine tablets [45,46].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Cladribine to Treat Relapsing Forms of Multiple Sclerosis

2017

View full text Add to dashboard Cite

Cladribine is a purine nucleoside analogue that selectively depletes peripheral lymphocytes without a major impact on cells of the innate immune system. An oral formulation of cladribine has been developed to be given as short courses over two annual cycles. Oral cladribine results in the peripheral depletion of lymphocytes that is gradual, occurring over several weeks, and is not associated with a cell lysis syndrome, has a greater impact on B cells than T cells, and is followed by gradual reconstitution of the peripheral lymphocyte counts over several months. Oral cladribine is effective in relapsing forms of multiple sclerosis. As a selective immune reconstitution therapy (SIRT), cladribine acts as a short-term immunosuppressant, relative to other maintenance immunosuppressive therapies that result in long-term immunosuppression. The main safety signal that has emerge relates primarily to herpes zoster infection, which was more common in patients with higher grades of lymphopenia, in particular grade 3 and 4 lymphopenia. Data from the oral cladribine extension trial and safety register, and reanalysis of the pivotal phase III trial has indicated that oral cladribine is unlikely to be associated with an increased short- to intermediate-term risk of malignancy.

show abstract

Section: Safety and Tolerabilitymentioning

confidence: 99%

Cladribine to Treat Relapsing Forms of Multiple Sclerosis

2017

View full text Add to dashboard Cite

show abstract

“…Experience derived from use in transplantation reveals that the major long-term toxicities limiting the use of immunosuppressive regimens are opportunistic infections and malignancies. 48 With the opportunistic infections observed with use of natalizumab, 3 along with opportunistic infections and malignancies observed in several of the recently completed trials with use of some of the emerging agents,49,50 these same concerns are now becoming part of the challenges associated with managing MS 48,51. Patients undergoing transplantation and the physicians providing their care face a continually moving target as they provide antimicrobial prophylaxis for known threats, such as Pneumocystis carinii and cytomegalovirus (CMV) wherein a new organism emerges, causing a new host of challenges.…”

Section: Risks and Benefits Of Emerging Therapiesmentioning

confidence: 99%

“…AEs in the CLARITY trial were similar to those reported in the parenteral dosing studies. However, in addition, there were 4 malignancies reported in the cladribine treatment groups (none in the placebo group) during the 96-week trial (1 case each of cervical, ovarian, and pancreatic cancer, as well as a case of malignant melanoma) 49. A fifth case of cancer was reported in a woman who developed a choriocarcinoma when she became pregnant 6 months after study completion 49,69.…”

Section: Oncology Agents In Development For the Treatment Of Msmentioning

confidence: 99%

Risks vs benefits of glatiramer acetate: a changing perspective as new therapies emerge for multiple sclerosis

Johnson¹

2010

TCRM

View full text Add to dashboard Cite

An understanding of the risks, benefits, and relative value of glatiramer acetate (GA) in multiple sclerosis (MS) has been evolving based on recently completed head-to-head studies: REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease); BEYOND (Betaseron Efficacy Yielding Outcomes of a New Dose); and BECOME (BEtaseron vs COpaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3-Tesla MRI Endpoints). Outcomes in the primary endpoints of these trials showed no significant differences between GA and high-dose beta-interferons (IFNβs). Results of the PreCISe (Early GA Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis [CDMS] in Subjects Presenting With a Clinically Isolated Syndrome [CIS]) trial led to the US Food and Drug Administration approval of GA in patients with a CIS. Furthermore, the ongoing follow-up study to the original pivotal GA trial, now extending beyond 15 years, continues to support the safety of GA. Currently, GA and IFNβs are no longer the only immunomodulators available for MS. Introduction of the monoclonal antibody, natalizumab (Tysabri®; Biogen Idec, Inc., Cambridge, MA, USA) provides an alternative immunomodulator for MS and has changed the therapeutic landscape dramatically. However, the rare but serious cases of progressive multifocal leukoencephalopathy that have occurred with natalizumab have raised concerns among clinicians and patients about using this agent and some of the emerging agents. The potential risks and benefits of the emerging therapies (cladribine, alemtuzumab, rituximab, fingolimod, laquinimod, teriflunomide, and dimethyl fumarate) based on phase II/III trials, as well as their use for indications other than MS, will be presented. This review provides available data on GA, natalizumab, and the emerging agents to support new developments in our understanding of GA and how its long-standing role as a first-line therapy in MS will evolve within the increasingly complex MS therapeutic landscape.

show abstract

“…A successful pregnancy has been reported in a patient treated with cladribine for hairy cell leukaemia [63]. Normal-term live births were also reported in two patients who received oral cladribine, and in the partner of a patient who received cladribine tablets in the CLARITY study [64]. However, since cladribine has been shown to inhibit DNA synthesis, parenteral cladribine use in hairy cell leukaemia has been classified as Pregnancy Category D, indicating that it should not be administered during pregnancy.…”

Section: Safety Datamentioning

confidence: 99%

“…This study will primarily provide information on the longer term safety and tolerability of oral cladribine administered for an additional 3rd and 4th year in patients with RRMS. This is an important issue, as 2 patients from the CLARITY study have been reported to develop solid organ cancers (ovarian and pancreatic), as well as one patient with melanoma, and a precancerous carvical dysplasia/carcinoma in situ (stage 0) [64]. These are not the malignancies usually associated with immunosuppression and the time course from treatment administration to diagnosis was relatively short.…”

Section: Clarity and Clarity Extensionmentioning

confidence: 99%

Development of oral cladribine for the treatment of multiple sclerosis

et al. 2009

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the CNS in which autoreactive CD4+ and CD8+ T lymphocytes, B lymphocytes, antibodies, macrophages and cytokines synergize to attack myelin sheaths and injure underlying axons. Current disease-modifying drugs (DMDs) for MS require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Of all the potential new oral MS agents in development, cladribine is the only therapy with the potential for short-course dosing. Cladribine is an immunosuppressant that offers targeted, sustained regulation of the immune system and that has a well-characterized safety profile, derived from more than 15 years of use of the parenteral formulation in oncology indications and MS. This paper discusses the need for new MS therapies to improve treatment adherence, and reviews the mechanism of action, existing efficacy and safety data, and the clinical development of oral cladribine. The need for continuous risk monitoring for all new potent immunoactive drugs under development is emphasized. Preliminary results of the 96-week, double-blind, randomized, placebo-controlled, multicenter CLARITY (CLAdRIbine Tablets Treating MS OrallY) study are encouraging and provide the first complete phase III data on an oral DMD for MS.

show abstract

PO10-TU-39 Safety and tolerability of short-course oral treatment with cladribine tablets for relapsing-remitting multiple sclerosis (RRMS) in the 96-week, phase III, double-blind, placebo-controlled CLARITY study

Cited by 9 publications

References 0 publications

Cladribine to Treat Relapsing Forms of Multiple Sclerosis

Cladribine to Treat Relapsing Forms of Multiple Sclerosis

Risks vs benefits of glatiramer acetate: a changing perspective as new therapies emerge for multiple sclerosis

Development of oral cladribine for the treatment of multiple sclerosis

Contact Info

Product

Resources

About