Talk:Cladribine

message: This article says that “In patients with hairy cell leukemia, there is no benefit to using hormones such as filgrastim or Granulocyte macrophage colony-stimulating factor to raise white blood cell counts prophylactically,” with two citations, but I wonder whether that represents a truly neutral point of view.
The first citation points to an article that says there is no statistically significant difference in the number of patients who experience fevers, the number of days that the fevers last, or the number of patients admitted to the hospital between the filgrastim-treated group and the control group.  It is good that a study with non-statistically-significant results is published; however, the article itself points out that “It is possible that the interpretation of results may have been weakened by the lack of a concurrent, randomized control group and by the fact that the number of study subjects and events were insufficient to detect subtle differences. These results could also have been influenced by there being more splenectomized patients among the historic controls and only patients in the filgrastim group had received prior cladribine therapy.”  Although the lack of a statistically-significant result may mean that “the routine use of filgrastim as an adjunct to treatment with cladribine cannot be recommended for HCL patients” an alternative interpretation is simply that more study is needed.
The second citation points to an article whose abstract says that “GM-CSF protected from cladribine lymphotoxicity but did not improve neutropenia or febrile episodes,” but the full article requires payment, so I cannot see the extent to the data actually support the proposition that using GM-CSF is unnecessary.  If this is another article with a statistically-insignificant result, then it would seem that Wikipedia is assuming that a statistically insignificant result is equivalent to no benefit, or is taking the position that no evidence of benefit is equivalent to evidence of no benefit.  I do not think that it is the role of Wikipedia to take such positions.  (But even if the article actually provides evidence that there is no benefit, we should also be mindful that verifiability and neutrality are [ two different policies], and an article can be fully verifiable with reliable sources and still be non-neutral.)
Bwrs (talk) 00:44, 20 April 2013 (UTC)
replies: text: This is what the sources say.  Per WP:MEDRS, editors are not permitted to perform their own peer review to decide whether, in their personal opinion, the sources are justified in saying this.  Per WP:DUE, if all the independent sources say this, then we should, too.  (I'm sure that the manufacturer of this pricey drug would be happy to sell this drug to this tiny population anyway, but my PubMed search turns up nothing at all that supports prophylactic use, not even from the manufacturer.)  WhatamIdoing (talk) 15:17, 20 April 2013 (UTC)
thread_title:  granulocyte colony-stimulating factor 

message: I will start editing the article now. Before starting I want to withdraw the intended edit from 19th July 2016.
Suggested Revision: 
In 2010, a by mouth form of cladribine was studied for the treatment of multiple sclerosis. Russia was the first country to approve it for treatment of multiple sclerosis on July 12, 2010. It was also approved for the treatment of multiple sclerosis in Australia in September 2010. Other applications, including in Europe and North America, were initially rejected by drug regulatory agencies due to weak evidence of safety and efficacy. In June 2011, Merck withdrew all marketing applications for cladribine tablets, and to stop selling it cladribine tablets from the Russian and Australian markets, where it was approved. In addition, marketing authorization was withdrawn in Russia, but is still valid in Australia. Several clinical studies of the cladribine tablets formulation were allowed to complete and additional safety information was also collected in a long-term registry. In September 2015, Merck announced that it intends to submit cladribine tablets for the treatment of relapsing-remitting multiple sclerosis (RRMS) for registration in Europe. 
Reason: 
--Florian Schaub at Merck KGaA (talk) 19:25, 19 August 2016 (UTC)
replies: text: I rewrote most of this with better sources.  Not sure what happened to the mechanism of action and chemistry sections; I'll see about restoring that.  Wierd. Jytdog (talk) 04:49, 24 August 2016 (UTC)
thread_title:  Start editing 

message: My name is Florian Schaub from Merck KGaA. My aim is to make some changes in this article because we have found some misleading information. I've compiled the suggested changes which you can find herinafter. They all follow one pattern:
• Current text
• Suggested revision
• Reason
• Suggested reference
If someone has objections please let me know.
_Current text
Legal status:
AU: S4 (Prescription only)
CA: Rx-only
UK: POM (Prescription only)
_Suggested revision
Legal status (cladribine injection for intravenous infusion)1,2: prescription only
_Reason
Legal status referring to cladribine iv infusion specifically.
_Suggested reference
1. Leustat injection SmPC. https://www.medicines.org.uk/emc/medicine/6737. Accessed 16 October 2017.
2. Leustatin injection. http://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/leustatin_pi.pdf. Accessed 16 October 2017
_Current text
Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA.
_Suggested revision
Cladribine is a nucleoside analogue of deoxyadenosine. A chlorine substitution in the purine ring protects cladribine from degradation by the enzyme adenosine deaminase. Subsequent phosphorylation of cladribine to its active triphosphate form, 2 chlorodeoxyadenosine triphosphate (CdATP), is particularly efficiently achieved in lymphocytes. CdATP leads to lymphocyte reduction by inducing cellular apoptosis and interfering with the cell's ability to process DNA.
_Reason
Correction to clarify the mode of action of cladribine
_Suggested reference
Sigal DS et al. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood 2010;116:2884–96.
_Current text
Cladribine is used for as a first and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukemia and is administered by intravenous infusion.[4][6]
_Suggested revision
Cladribine is used as first- and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukemia and is administered by subcutaneous injection or intravenous infusion.[4][6]
_Reason
Correction of grammar.
Can be given subcutaneously or by infusion.
_Suggested reference
Leustat injection [EU] [Summary of Product Characteristics], July 2014. https://www.medicines.org.uk/emc/medicine/6737 [Accessed 24/7/17]
_Current text
It used, often in combination with other cytotoxic agents, to treat various histiocytoses, including Erdheim–Chester disease[7] and Langerhans cell histiocytosis,[9]
_Suggested revision
It is used, often in combination with other cytotoxic agents, to treat various histiocytoses, including Erdheim–Chester disease[8] and Langerhans cell histiocytosis.[9]
_Reason
Correction of grammar.
An additional reference is suggested as the current reference is not open access.
_Suggested reference
Histiocytosis Association. LCH in Adults. http://www.histio.org/page.aspx?pid=383 [Accessed 27 July 2017].
_Current text
In February 1991 Scripps began a collaboration with Johnson & Johnson to bring intravenous cladribine to market and by December of that year J&J had filed an NDA; cladrabine was approved by the FDA in 1993 for HCL as an orphan drug,[10] and was approved in Europe later that year.[11]:2
_Suggested revision
In February 1991 Scripps began a collaboration with Johnson & Johnson to bring intravenous cladribine to market and by December of that year J&J had filed an NDA; cladribine was approved by the FDA in 1993 for HCL as an orphan drug,[10] and was approved in Europe later that year.[11,NEW]
_Reason
Misspelling of cladribine.
Additional reference to support cladribine’s orphan drug status.
_Suggested reference
U.S. Food and Drug Administration. List of orphan products designations and approvals. http://www.fda.gov/ohrms/dockets/dailys/00/mar00/030100/lst0094.pdf [Accessed 24 July 2017].
_Current text
A meta-analysis of data from clinical trials showed that cladiribine did not increase the risk of cancer at the doses used in the clinical trials.
_Suggested revision
A meta-analysis of data from Phase III clinical trials showed that oral cladribine tablets did not increase the risk of cancer in patients with MS.
_Reason
Misspelling of cladribine. 
Clarification type of trials included in meta-analysis
_Suggested reference
Multiple Sclerosis News Today. Potential MS drug cladribine reported to have no impact on cancer incidence. https://multiplesclerosisnewstoday.com/2015/10/09/potential-ms-drug-cladribine-reported-to-have-no-impact-on-cancer-incidence/ [Accessed 25 July 2017].
_Current text
In 2015 Merck KGgA announced it would again seek regulatory approval with data from the completed clinical trials in hand,[23] 
_Suggested revision
In 2015 Merck KGaA announced it would again seek regulatory approval with data from the completed clinical trials in hand,[23]
_Reason
Misspelling of KGaA
Additional suggested reference to be added; the suggested additional reference is the original Merck press release.
_Suggested reference
Merck Group. Merck Intends to Submit Cladribine Tablets to Treat Multiple Sclerosis for Registration in Europe. http://news.merck.de/EMD/CC/NewsRelease.nsf/0/1C517A71C016A43BC1257EBC006B50C3/$FILE/CladribineEng.pdf [Accessed 24 July 2017]
_Current text
, and in 2016 the EMA accepted its application for review.[25]
_Suggested revision
In July 2016, Merck Serono Europe announced that the European Medicines Agency (EMA) had accepted for review the Marketing Authorisation Application (MAA) of cladribine tablets for the treatment of relapsing-remitting multiple sclerosis (RRMS) [1]. On 23 June 2017, Merck Serono Europe announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMA had issued a positive opinion for approval of Cladribine Tablets for the treatment of relapsing forms of MS (RMS) in patients with high disease activity [2]. On 25th August 2017, Merck Serono Europe announced that the European Commission (EC) granted marketing authorization for MAVENCLAD® 10 mg (Cladribine Tablets) for the treatment of highly active RMS in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland [3].
_Reason
Correction to specify that cladribine tablets has received a positive CHMP opinion
_Suggested reference
1. Merck Group. Merck receives European Medicines Agency acceptance for review of Marketing Authorization Application for cladribine tablets. https://www.merckgroup.com/content/corporate/communications/mkgaa-global/en/news/marketing-authorization-application-for-cladribine-18-07-2016.html  [Accessed 25 July 2017].
2. EMA Committee for Medicinal Products for Human Use (CHMP) Summary of opinion.
http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/004230/WC500229786.pdf [Accessed 25 July 2017]
3. European Commission Grants Approval for Mavenclad (Cladribine Tablets) hhttp://ec.europa.eu/health/documents/community-register/2017/20170822138481/dec_138481_en.pdf [Accessed 01 September 2017]
--Florian Schaub at Merck KGaA (talk) 14:06, 18 October 2017 (UTC)
thread_title:  Announcement of Changes 

message: As nobody had any objections to my announcement of changes from the 18th October I will now start editing the article.
--Florian Schaub at Merck KGaA (talk) 08:40, 7 November 2017 (UTC)
thread_title:  Start to edit the article