Talk:Cladribine

granulocyte colony-stimulating factor
This article says that &#8220;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,&#8221; 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 &#8220;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.&#8221; Although the lack of a statistically-significant result may mean that &#8220;the routine use of filgrastim as an adjunct to treatment with cladribine cannot be recommended for HCL patients&#8221; an alternative interpretation is simply that more study is needed.

The second citation points to an article whose abstract says that &#8220;GM-CSF protected from cladribine lymphotoxicity but did not improve neutropenia or febrile episodes,&#8221; 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)


 * 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)

Factual Corrections
My name is Florian Schaub at Merck KGaA. My aim is to make some changes in this article, because we have identified some misleading information. I have provided clearly arranged suggestions that you can see below on the talk page. They all follow the same pattern: Please let me know if anyone has concerns.
 * Current Version
 * Suggested Revision (Suggested changes are bold)
 * Reason
 * Suggested Reference (if needed)

_Current Text: Routes of administration: Intravenous, subcutaneous, oral Suggested Revision: Routes of administration: Intravenous, subcutaneous (liquid), oral (tablets) Reason: Cladribine tablets (oral formulation) not currently available.

_Current Text: Legal status: Suggested Revision: Legal status (Leustatin): Reason: Marketing of Leustatin has been discontinued in the US. Suggested Additional Reference: Drugs@FDA. Leustatin – Drug details. https://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails [Accessed 24 Jun 2016].
 * AU: S4 (Prescription only)
 * CA: Rx-only
 * UK: POM (Prescription only)
 * US: Rx-only)
 * AU: S4 (Prescription only)
 * CA: Rx-only
 * UK: POM (Prescription only)
 * US: Rx-only)

_Current Text: Metabolism: Mostly via intracellular kinases; 15–18% if excreted unchanged Suggested Revision: Metabolism: Mostly via intracellular kinases; 15–18% is excreted unchanged Reason: Correction of typographical error; the reference reads “…is excreted unchanged”. Suggested Additional Reference: Litak Australian PI.

_Current Text: Biological half-life: 5.4 hours (range 3–22 hours) Suggested Revision: Terminal elimination half-life Biological half-life : Approximately 10 hours after both intravenous infusion and subcutaneous bolus injection Reason: Changes suggested to match the Litak Australian PI. Suggested Additional Reference: Litak Australian PI.

_Current Text: Formula: C10H12C1N5O3 Suggested Revision: Formula: C10H12ClN5O3 Reason: ‘1’ corrected to ‘I’ [Cl for chlorine (lower case ‘L’)]. Suggested Additional Reference: ChEMBL. Compound report card. https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL1619 [Accessed 03 Jun 2016].

_Current Text: Cladribine is a medication used to treat hairy cell leukemia (HCL, leukemic reticuloendotherliosis) and multiple sclerosis. Suggested Revision: Cladribine is a medication used to treat hairy cell leukemia (HCL; '''leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. and multiple sclerosis .''' Reason: Correction of the spelling of ‘reticuloendotheliosis’. Cladribine is not currently licensed for the treatment of multiple sclerosis, and is licensed for the treatment of B-cell chronic lymphocytic leukemia in the UK. Suggested Additional Reference: Litak EU SPC. Leustat UK SPC.

_Current Text: Its chemical name is 2-chlorodeoxyadenosine (2CDA). Suggested Revision: Its chemical name is 2-chloro-2’-deoxyadenosine (2CdA).

_Current Text: As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss. Suggested Revision: As a purine analog, it is a synthetic  anti-cancer chemotherapy agent that '''targets lymphocytes. also and selectively''' suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. ''' It is easily destroyed by normal cells except for blood cells Cladribine is activated only by lymphocytes, and non-activated cladribine is removed quickly from all other cells. This means that there is, with the result that it produces relatively few side effects and results in ''' very little non-target cell loss. Reason: Scientific clarification. Clarification regarding the mechanism leading to little non-target cell loss. Suggested Additional Reference: Litak EU SPC. Leist TP, Weissert R. Clin Neuropharmacol 2011;34:28–35.

_Current Text: Many people have mild rashes and many have nausea; the nausea generally does not lead to vomiting. Suggested Revision: At the dosage used to treat HCL in two clinical trials, 16% of people had rashes and 22% had nausea; the nausea generally did not lead to vomiting. Reason: Specific information on the actual percentage of patients affected by rashes and nausea is available in the Leustatin FDA PI. We have suggested giving specific values for the percentages of patients experiencing mild rashes and nausea. Please note that Leustatin marketing has now discontinued in the US. Suggested Additional Reference: Leustatin FDA PI for cladribine

_Current Text: 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 multiple sclerosis on July 12, 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 application for cladribine tablets, and to stop selling it in Russia and Australia, where it had been approved. 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: Correction of typographical error (missing word ‘of’ inserted). Corrective information to clarify the history of cladribine tablets. Suggested Additional Reference: Therapeutic Goods Administration. Movectro withdrawn. https://www.tga.gov.au/alert/movectro-withdrawn [Accessed 08 Jul 2016]. Merck. Merck intends to submit cladribine tablets to treat multiple sclerosis for registration in Europe. http://www.merckgroup.com/en/media/extNewsDetail.html?newsId=1C517A71C016A43BC1257EBC006B50C3&newsType=1 [Accessed 24 Jun 2016].

_Current Text: Histiocytosis Association (http://www.histio.org) Suggested Revision: '''Histiocytosis Association. Erdheim-Chester disease. http://www.histio.org/page.aspx?pid=405#.V1BDvuTaHqk [Accessed 03 Jun 2016].''' Reason: Suggest revision to the specific source of information rather than the association’s home page. Suggested Additional Reference: Histiocytosis Association. Erdheim-Chester disease. http://www.histio.org/page.aspx?pid=405#.V1BDvuTaHqk [Accessed 03 Jun 2016].

--Florian Schaub at Merck KGaA (talk) 10:30, 19 July 2016 (UTC)

Start editing
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)
 * 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)

More Factual Corrections
We have identified more misleading information that we announce below before editing them. We have provided them in the same way and same structure.
 * Current Text
 * Suggested Revision (Suggested changes are bold)
 * Reason
 * Suggested Reference (if needed)

Please let me know if anyone has concerns. Otherwise I will do the edits in two weeks.

1) Current Text: The failure was a blow to Merck KGgA, leading to a reorganization, layoffs, and closing the Swiss facility where Serono had arisen. Suggested Revision: The failure was a blow to Merck KGaA, contributing leading  to a reorganization, layoffs, and closing the Swiss facility where Serono had arisen. Reason: Other sources suggested that there were additional factors that may have contributed to the reorganization e.g. the European regulatory rejection of Erbitux and increased competition associated with Rebif in the MS market. Suggested Additional Reference: Firstword Pharma. Merck KGaA announces cost-cutting initiative, potential job cuts. http://www.firstwordpharma.com/node/954881?tsid=17#axzz4IAIZS6Ad [Accessed 23 Aug 2016]. Bloomberg. Merck KGaA to Close Merck Serono Site in Geneva, Cut Jobs. http://www.bloomberg.com/news/articles/2012-04-24/merck-kgaa-to-close-merck-serono-site-in-geneva-cut-jobs [Accessed 23 Aug 2016].

2) Current Text: The concerns were that several cases of cancer had arisen, and the ratio of benefit to harm was not clear to regulators. Suggested Revision: The concerns were that several cases of cancer had arisen, and the ratio of benefit to harm was not clear to regulators. Subsequent to this, a meta-analysis of Phase III trials reported that there was no evidence for increased cancer risk in patients with multiple sclerosis taking cladribine tablets. Reason: Clarification that meta-analyses of Phase III trials have reported no increase in cancer incidence associated with cladribine tablets. Suggested Additional 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 Aug 2016]. Pakpoor J et al. Neurology 2015; October 1 [Epub ahead of print]. doi: 10.1212/NXI.0000000000000158.

3) 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 or by subcutaneous injection, depending on the formulation. Suggested Revision: No revision – additional reference suggested at the end of this sentence. Cladribine is used as a first and second-line treatment. Reason: The suggested additional reference is the Summary of Product Characteristics for Litak 2 mg/ml solution for injection, for which the recommended posology for hairy cell leukemia is subcutaneous bolus injection. Out of the three currently referenced sources, one (reference 7) does not mention subcutaneous administration and another (reference 4) mentions that subcutaneous administration is not recommended but that there is data for its use in MS (unlicensed). Reference 6 is not open access. Suggested Additional Reference: [LITAK 2 mg/ml solution for injection] [EU] [Summary of Product Characteristics], June 2010. http://www.medicines.org.uk/emc/medicine/20597 [Accessed 23 Aug 2016].

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. 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 cladrabine  was approved by the FDA in 1993 for HCL as an orphan drug. Reason: Misspelling of cladribine and an additional reference to support cladribine’s orphan drug status. Suggested Additional 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 23 Aug 2016].

4) Current Text: It used, often in combination with other cytotoxic agents, to treat various histiocytoses, including Erdheim–Chester disease and Langerhans cell histiocytosis Suggested Revision: …to treat various classes of histiocytosis histiocytoses … Reason: Histiocytosis is an umbrella term so does not need to be pluralized.

5) Current Text: It used, often in combination with other cytotoxic agents, to treat various histiocytoses, including Erdheim–Chester disease and Langerhans cell histiocytosis Suggested Revision: Additional reference suggested for use of cladribine in Langerhans cell histiocytosis Reason: An additional reference is suggested as the current reference is not open access. Suggested Additional Reference: Histiocytosis Association. LCH in Adults. http://www.histio.org/page.aspx?pid=383 [Accessed 23 Aug 2016].

6) Current Text: In 2015 Merck KGgA announced it would again seek regulatory approval with data from the completed clinical trials in hand Suggested Revision: No revision – additional reference suggested Reason: The suggested additional reference is the original Merck press release. Suggested Additional Reference: Merck Group. Merck Intends to Submit Cladribine Tablets to Treat Multiple Sclerosis for Registration in Europe. http://www.merckgroup.com/en/media/extNewsDetail.html?newsId=1C517A71C016A43BC1257EBC006B50C3&newsType=1 [Accessed 24 Aug 2016].

7) Current Text: In 2015 Merck KGgA announced it would again seek regulatory approval with data from the completed clinical trials in hand, and in 2016 the EMA accepted its application for review. Suggested Revision: In 2015 Merck KGgA announced it would again seek regulatory approval with data from the completed clinical trials in hand. and in 2016 the EMA accepted its application for review.  In July 2016, Merck 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). Reason: Correction to specify that cladribine tablets are under review for the treatment of RRMS. Suggested Additional Reference: Merck. Merck receives European Medicines Agency acceptance for review of Marketing Authorization Application for cladribine tablets. http://www.merckgroup.com/en/media/extNewsDetail.html?newsId=57F6B32E5CD8E3AAC1257FF100307005&newsType=1 [Accessed 4 Aug 2016].

--Florian Schaub at Merck KGaA (talk) 13:05, 29 September 2016 (UTC)
 * Thanks for your note. Will take some time to evaluate all this. In the future please consider bringing stronger sources, and independent ones; press releases are not optimal.  Jytdog (talk) 15:37, 29 September 2016 (UTC)
 * I numbered the items above.... when you provide references to journal articles, would you please provide the pubmed ID (PMID). For example the reference in Item 2 is  and as you can see the WP software automatically converts that to a link to pubmed.  much easier to deal with.
 * 1) ✅
 * 2) ✅
 * 3) ✅ Thanks for pointing out the error; I removed the subQ. a reference not being open access, is irrelevant.   I removed  as a ref, as it is a primary source that fails MEDRS.
 * 4) ✅
 * 5) that is not a MEDRS source. not done.  per WP:MEDRS we need a literature review published in good quality journal or a statement by a major medical/scientific body.
 * 6) not interested in using a press release; independent sources are highly preferred in WP
 * 7) WP:NOTNEWS. We can add something when there is a decision
 * -- Jytdog (talk) 03:48, 30 September 2016 (UTC)

Announcement of Changes
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)

Start to edit the article
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)

2021 Page factual update
My name is Samer Fahmy, I am reaching out on behalf of the Merck KGaA Neurology and Immunology Global Business Franchise Team, handling Cladribine tablets. Following my colleague Florian Schaub’s updates, we would like to add further detail to the current page, and are proposing some edits and restructuring.

Through these updates we aim to:
 * Revise the text to fully align with the MAVENCLAD Summary of Product Characteristics
 * Update with more recent information and clinical trial data
 * Distinguish between outcomes for multiple sclerosis and hairy cell leukemia in terms of adverse effects, safety and efficacy
 * Update and correctly reference the mechanism of action of cladribine, including an additional phosphorylation step
 * Reposition the ‘Mechanism of action’ before ‘Adverse effects’, allowing readers to understand the mechanism of action and how this can cause certain side effects
 * Provide additional information on medical uses for multiple forms of multiple sclerosis
 * Separate the ‘History’ section to provide clearer flow and context to the two indications
 * Reposition ‘Use in clinical practice’ above ‘Efficacy and safety’ to provide further context to clinical use

Please see below a list of the proposed revisions and associated rationale. Please let me know if anyone has any concerns.

SamerFahmy (talk) 14:56, 21 May 2021 (UTC)

Responses to Samer Fahmy's proposal above

 * @SamerFahmy, some of these sources are a bit on the old side. The ideal is to cite sources from the last five years, but for some things (e.g., rare diseases) we stretch a point and reach back for 10 years.  Is there any chance that the older sources could be replaced with something fairly new?  (For clarity, I don't want you to propose a worse source just to have a newer one.  Also, review articles, textbooks and reputable reference works are fine, too, but the press release is unlikely to work.  If you haven't seen it before, then Identifying reliable sources (medicine) may be helpful.)  WhatamIdoing (talk) 04:43, 15 June 2021 (UTC)


 * @WhatamIdoing, The new references incorporated as part of my updates are in bold, the only one older than 5 years is the Leist reference (2011). It is related to MoA and all recent publications are citing this one. It is usually a best practice to cite the original publication when developing new materials. Therefore, I would suggest citing this reference for the page update. As for the use of the press release, this is the only way I could reference the approval of Cladribine Tablets for treating MS in over 80 countries. Such information has not been be found in a clinical publication to date. Is this approach acceptable for you?
 * SamerFahmy (talk) 13:11, 16 June 2021 (UTC)


 * @SamerFahmy, Seems mostly fine to me. Appreciate the effort to describe the changes in detail. However, mentioning the approval "in over 80 countries" makes it sound like an advert, and if it has to reference a press release I'd leave it out until we have secondary sources that discuss how many countries it is approved in. - Rod57 (talk) 03:46, 4 July 2021 (UTC)