Revision as of 13:41, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 460512580 of page Sarilumab for the Chem/Drugbox validation project (updated: 'CAS_number'). |
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{{Short description|Human monoclonal antibody medication}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{update|lack of effectiveness against the ]|date=January 2022}} |
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{{Drugbox |
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{{Use dmy dates|date=August 2024}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 458637221 |
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| verifiedrevid = 464387301 |
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| type = mab |
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| type = mab |
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| image = |
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| image = |
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| alt = |
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| alt = |
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| caption = |
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<!-- Monoclonal antibody data --> |
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| mab_type = mab |
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| mab_type = mab |
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| source = u |
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| source = u |
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| target = ] |
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| target = ] |
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| tradename = |
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<!-- Clinical data --> |
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| Drugs.com = |
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| MedlinePlus = |
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| pronounce = |
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| tradename = Kevzara |
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| Drugs.com = {{Drugs.com|monograph|sarilumab}} |
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| MedlinePlus = a617032 |
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| DailyMedID = Sarilumab |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category= |
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| pregnancy_category= |
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| routes_of_administration = ] |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| class = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| ATC_prefix = L04 |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> |
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| ATC_suffix = AC14 |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| ATC_supplemental = |
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| routes_of_administration = |
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<!-- Legal status --> |
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| bioavailability = |
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| protein_bound = |
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| legal_AU = S4 |
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| metabolism = |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| elimination_half-life = |
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| excretion = |
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| legal_BR_comment = |
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| legal_CA = Rx-only |
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| legal_CA_comment = <ref>{{cite web | title=Arthritis | website=] | date=8 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/arthritis.html | access-date=13 April 2024}}</ref><ref>{{cite web | title=Regulatory Decision Summary for Kevzara | website=Drug and Health Products Portal | date=12 January 2017 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS00205 | access-date=13 April 2024}}</ref> |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Kevzara FDA label">{{cite web | title=Kevzara- sarilumab injection, solution | website=DailyMed | date=17 June 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=827bc01c-d379-4266-a18c-c7f904b76af3 | access-date=26 August 2024}}</ref> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Kevzara EPAR">{{cite web | title=Kevzara EPAR | website=European Medicines Agency (EMA) | date=23 June 2017 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kevzara | access-date=26 August 2024}}</ref> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = 80% |
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| protein_bound = |
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| metabolism = likely ]s |
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| metabolites = |
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| onset = |
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| elimination_half-life = 21 days (steady-state, estimated) |
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| duration_of_action = |
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| excretion = |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = <!-- blanked - oldvalue: 1189541-98-7 --> |
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| CAS_number = 1189541-98-7 |
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| CAS_supplemental = |
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| ATC_prefix = none |
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| ATC_suffix = |
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| PubChem = |
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| PubChem = |
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| IUPHAR_ligand = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = NA |
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| ChemSpiderID = none |
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| C=6388 | H=9918 | N=1718 | O=1998 | S=44 |
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| UNII_Ref = |
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| UNII = NU90V55F8I |
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| molecular_weight = 144.13 kDa |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D10161 |
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| ChEBI_Ref = |
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| ChEBI = |
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| ChEMBL_Ref = |
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| ChEMBL = |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = |
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<!-- Chemical and physical data --> |
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| C=6388 | H=9918 | N=1718 | O=1998 | S=44 |
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}} |
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}} |
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'''Sarilumab''', sold under the brand name '''Kevzara''', is a human ] medication against the ] ].<ref>{{cite web|title=Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab| website= ama-assn.org |publisher= ]| url= http://www.ama-assn.org/resources/doc/usan/sarilumab.pdf |url-access=subscription }}</ref> ] and ] developed the drug for the treatment of ] (RA), for which it received US ] approval on 22 May 2017 and ] approval on 23 June 2017.<ref>{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004254/human_med_002114.jsp&mid=WC0b01ac058001d124|title=Kevzara: Authorisation details|publisher=]|access-date=28 September 2017|archive-date=27 September 2017|archive-url=https://web.archive.org/web/20170927060452/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F004254%2Fhuman_med_002114.jsp&mid=WC0b01ac058001d124|url-status=dead}}</ref> |
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Development in ] has been suspended after the drug failed to show clinical benefit over ] in a phase II trial.<ref name=SR2011>{{cite press release| url= http://investor.regeneron.com/releasedetail.cfm?releaseid=590869| title= Sanofi and Regeneron Report Positive Phase 2b Trial Results with Sarilumab in Rheumatoid Arthritis| date= 12 July 2011| website= regeneron.com| publisher= Regeneron | location= Paris & Tarrytown, New York}}</ref> |
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==Medical uses== |
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Sarilumab is used for the treatment of moderately to severely active rheumatoid arthritis in people who have not responded to, or did not tolerate, more conventional treatments.<ref>{{cite journal | vauthors = Boyce EG, Rogan EL, Vyas D, Prasad N, Mai Y | title = Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis | journal = Annals of Pharmacotherapy | date = Feb 2018 | pmid = 29482351 | doi = 10.1177/1060028018761599 | volume=52 | issue = 8 | pages=780–791| s2cid = 3580054 }}</ref> It can be used alone or in combination with ] or other ]s (DMARDs).<ref name="EPAR">{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004254/WC500230068.pdf|title=Kevzara: EPAR – Product Information|publisher=]|date=26 September 2017|access-date=29 November 2017|archive-date=18 June 2018|archive-url=https://web.archive.org/web/20180618040428/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004254/WC500230068.pdf|url-status=dead}}</ref><ref name="Drugs.com">]: Sarilumab {{Drugs.com|monograph|sarilumab}}. Accessed 29 November 2017.</ref> |
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==Contraindications== |
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In the European Union, sarilumab is contraindicated in people with active, severe infections.<ref name="EPAR" /> While this is not listed as a contraindication under the US FDA approval, there is a ] that recommends testing for hidden ] infection before treatment and monitoring for signs of an infection during therapy with sarilumab.<ref name="Drugs.com" /> |
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==Side effects== |
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The MONARCH trial suggested a significantly higher incidence of ] in patients receiving 200 mg sarilumab every 2 weeks, compared to patients being treated with ] (13.6% vs 0.5%). However, infection rates were similar between both groups (28.8% vs 27.7%).<ref name=MPT-monarch/> |
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Other common side effects that occurred in 1% to 10% of patients included ] (low ] count), infections of the ] and the ], oral herpes, ], and ]s such as pain or redness.<ref name="EPAR" /> |
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==Clinical trials== |
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===Rheumatoid arthritis=== |
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On 15 May 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled.<ref>{{Cite web |url=http://en.sanofi.com/Images/33027_20130515_sari_en.pdf |title=Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013 |access-date=15 May 2013 |archive-date=19 January 2017 |archive-url=https://web.archive.org/web/20170119105220/http://en.sanofi.com/Images/33027_20130515_sari_en.pdf |url-status=dead }}</ref> |
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In June 2015, a phase III trial (with ]) for RA reported meeting its three coprimary endpoints.<ref name=J2015>{{cite journal | vauthors = Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, Rohane P, van Hoogstraten H, Garg A, Fan C, van Adelsberg J, Weinstein SP, Graham NM, Stahl N, Yancopoulos GD, Huizinga TW, van der Heijde D | title = Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study | journal = Arthritis & Rheumatology | volume = 67 | issue = 6 | pages = 1424–37 | date = June 2015 | pmid = 25733246 | doi = 10.1002/art.39093 | doi-access = free }}</ref> |
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In November 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points).<ref name=P3-2015>{{cite web | first = Tracey | last = Walker | name-list-style = vanc | url = http://formularyjournal.modernmedicine.com/formulary-journal/news/sarilumab-effective-broad-range-ra-patients-study | archive-url = https://web.archive.org/web/20151121015656/http://formularyjournal.modernmedicine.com/formulary-journal/news/sarilumab-effective-broad-range-ra-patients-study | archive-date = 21 November 2015 | url-status = dead | title = Sarilumab effective in broad range of RA patients: Study | work = Formulary Watch }}</ref> |
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In November 2016, the ''MONARCH'' phase III trial comparing sarilimab to ] (an anti-TNF) found sarilumab superior at reducing the ]-ESR score in patients with RA after 24 weeks.<ref name=MPT-monarch>{{cite journal | vauthors = Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, van Hoogstraten H, Bauer D, Ignacio Vargas J, Lee EB | title = Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial | journal = Annals of the Rheumatic Diseases | volume = 76 | issue = 5 | pages = 840–847 | date = May 2017 | pmid = 27856432 | pmc = 5530335 | doi = 10.1136/annrheumdis-2016-210310 }}</ref> |
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In July 2019, a multi-center trial was launched to study 'Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis.' <ref>{{Cite web|url=http://med.stanford.edu/cardiac-sarcoidosis/publications.html|title=More Information|website=Sarcoidosis Program|language=en|access-date=9 August 2019|archive-date=9 August 2019|archive-url=https://web.archive.org/web/20190809164955/http://med.stanford.edu/cardiac-sarcoidosis/publications.html|url-status=dead}}</ref> |
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==History== |
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In October 2016, the U.S. ] (FDA) refused approval for marketing as a treatment for rheumatoid arthritis due to ] (GMP) violations.<ref name=MPT-monarch/> The drug was eventually approved by the FDA on 22 May 2017. |
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== Research == |
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===COVID-19=== |
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A study of 420 patients was halted in September 2020, due to lack of demonstrated effectiveness in treating ] symptoms.<ref></ref> |
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On 7 January 2021, following results from the REMAP-CAP trial, ] and Sarilumab were added to the UK recommended list for COVID-19 treatment, the ] is 12, meaning for every 12 intensive care unit patients treated 1 additional person survives compared to treatment as normal, also speeding up patients' recovery and reducing the length of time that critically-ill patients need to spend in intensive care by about a week |
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<ref>{{Cite news|first=Michelle|last=Roberts|date=7 January 2021|title=Two more life-saving Covid drugs discovered|language=en-GB|work=BBC News|url=https://www.bbc.co.uk/news/health-55574662|access-date=7 January 2021}}</ref> |
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Tocilizumab seems to be more beneficial, whereas the clinical efficacy of Sarilumab has not been established as data on decreased mortality was often not significant. The number of trials did not allow for the identification of a specific patient subset that benefits the most from Sarilumab treatment, yet (May 2022).<ref>- Yu SY, Koh DH, Choi M, et al. Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis. Emerg Microbes Infect. 2022;11(1):1154-1165. doi:10.1080/22221751.2022.2059405</ref><ref>- Sivapalasingam S, Lederer DJ, Bhore R, et al. Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19: A Randomized Clinical Trial . Clin Infect Dis. 2022;ciac153. doi:10.1093/cid/ciac153</ref> |
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== References == |
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{{reflist}} |
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== Further reading == |
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{{refbegin}} |
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* {{cite journal | vauthors = Bermejo I, Ren S, Simpson E, Clowes M, Scott DL, Young A, Stevenson M | title = Sarilumab for Previously-Treated Moderate or Severe Rheumatoid Arthritis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal | journal = PharmacoEconomics | volume = 36| issue = 12| pages = 1427–1437| date = June 2018 | pmid = 29882210 | doi = 10.1007/s40273-018-0677-7 | s2cid = 46969760 | url = http://eprints.whiterose.ac.uk/131862/3/Pharmacoeconomics%20sarilumab%20v4.pdf }} |
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* {{cite journal | vauthors = Genovese MC, van Adelsberg J, Fan C, Graham NM, van Hoogstraten H, Parrino J, Mangan EK, Spindler A, Huizinga TW, van der Heijde D | title = Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes | journal = Rheumatology | volume = 57 | issue = 8 | pages = 1423–1431 | date = August 2018 | pmid = 29746672 | pmc = 6055572 | doi = 10.1093/rheumatology/key121 }} |
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* {{cite journal | vauthors = McCarty D, Robinson A | title = Efficacy and safety of sarilumab in patients with active rheumatoid arthritis | journal = Therapeutic Advances in Musculoskeletal Disease | volume = 10 | issue = 3 | pages = 61–67 | date = March 2018 | pmid = 29492111 | pmc = 5802641 | doi = 10.1177/1759720X17752037 }} |
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* {{cite journal | vauthors = Raimondo MG, Biggioggero M, Crotti C, Becciolini A, Favalli EG | title = Profile of sarilumab and its potential in the treatment of rheumatoid arthritis | journal = Drug Design, Development and Therapy | volume = 11 | pages = 1593–1603 | date = 2017 | pmid = 28579757 | pmc = 5447699 | doi = 10.2147/DDDT.S100302 | doi-access = free }} |
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{{refend}} |
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{{Immunosuppressants}} |
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{{Monoclonals for immune system}} |
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{{Interleukin receptor modulators}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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