Guidelines
doi:10.1093/rheumatology/kev404
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I:standard and biologic dia modifying anti-rheumatic drugs and corticosteroids
挨的近义词Julia Flint 1,Sonia Panchal 2,Alice Hurrell 3,Maud van de Venne 4,Mary Gayed 5,Karen Schreiber 6,7,Subha Arthanari 8,Joel Cunningham 3,Lucy Flanders 3,Loui Moore 9,Amy Crossley 10,Neetha Purushotham 3,Amisha Desai 5,
Madeleine Piper 11,Mohamed Nisar 8,Munther Khamashta 6,David Williams 3,Caroline Gordon 12,13and Ian Giles 1,3on behalf of the BSR and BHPR Standards,Guidelines and Audit Working Group
Key words:rheumatic dia,pregnancy,breastfeeding,prescribing,corticosteroids,hydroxychloroquine,DMARDs,biologics
Executive Summary
Scope and purpo of the guideline
Need for guidelines
The prescribing of many drugs in pregnancy is compli-cated by a lack of knowledge regarding their compatibility leading to patient misinformation and withdrawal/denial of
dia-ameliorating therapies.This situation should be avoided becau active rheumatic dia is associated with adver pregnancy outcomes [1]and there is grow-ing evidence of drug safety in
pregnancy.
1
Centre for Rheumatology Rearch,UCL Division of Medicine,University College London,London,2Department of Rheumatology,University Hospitals of Leicester,Leicester,3Womens Health,University College London Hospital,London,4Obstetrics and Gynaecology,Frimley Park Hospital,Surrey,5Department of
Rheumatology,University Hospital Birmingham NHS Foundation Trust,Birmingham,6Department of Rheumatology,Guy’s and St Thomas’NHS Foundation Trust,London,UK,7Department of Rheumatology,Copenhagen University Hospital,Rigshospitalet,Denmark,8
Department of Rheumatology,Burton Hospitals NHS Trust,Burton-upon-Trent,9Rheumatic and Musculoskeletal Dia Unit,Our Lady’s Hospice and Care Services,Dublin,Ireland,10Department of Rheumatology,University College London Hospital,London,11
Department of Rheumatology,Aneurin Bevan University Health Board,Newport,UK,12Department of Rheumatology,Sandwell and West Birmingham Hospitals NHS Trust and 13Division of Immunity and Infection,University of Birmingham,Birmingham,UK
Correspondence to:Ian Giles,Centre for Rheumatology Rearch,UCL Division of Medicine,Room 411,Rayne Institute,5University Street,London,UK.E-mail:i.giles@ucl.ac.uk
Submitted 17June 2015;revid version accepted 4November 2015RHEUMATOLOGY录像英语
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Rheumatology Advance Access published January 12, 2016 by guest on January 12, 2016
Objectives of the guideline
To provide evidence-bad recommendations,which do not imply a legal obligation,for clinicians when prescribing anti-rheumatic drugs before/during pregnancy and breastfeeding that update previous recommendations [2,3].For recommendations on prescribing other drugs in pregnancy and breastfeeding e the British Society of Rheumatology(BSR)and British Health Professionals in Rheumatology(BHPR)guidelines part II[4].
Target audience
Health professionals directly involved in managing pa-tients with rheumatic dia in the UK who are(or plan-ning to become)pregnant and/or breastfeeding,men planning to conceive and patients who have accidentally conceived while taking the medications.
The areas the guideline does not cover
This guideline does not cover the management of infertility or the indications for the drugs in specific rheumatic dias in pregnancy.
Key recommendations from the guidelines
Specific questions were considered in relation to each drug. Should it be stopped pre-conception?Is it compatible with pregnancy?Is it compatible with breastfeeding?Where pos-sible,recommendations are made regarding compatibility with paternal exposure.The findings are summarized in Table1.A description of evidence and full recommendations are given in the full guideline provided as supplementary data,available at Rheumatology Online. Recommendations for corticosteroids in pregnancy and breastfeeding
(i)Prednisolone is compatible with each trimester of preg-
nancy[level of evidence(LOE)1++,grade of recommen-dation(GOR)A,strength of agreement(SOA)100%]. (ii)Prednisolone is compatible with breastfeeding (LOE2À,GOR D,SOA98.9%).
(iii)Prednisolone is compatible with paternal exposure (LOE2+,GOR D,SOA98.9%).
(iv)Methylprednisolone has rates of placental trans-fer similar to prednisolone with equivalent anti-inflammatory effects at80%of prednisolone do and would therefore be expected to be compatible with pregnancy,breastfeeding and paternal expos-ure(LOE4,GOR D,SOA93.7%). Recommendations for HCQ in pregnancy and breastfeeding
(i)HCQ remains the antimalarial of choice in women
planning a pregnancy with rheumatic dia in need of treatment and should be continued during pregnancy(LOE1++,GOR A,SOA100%).为你唱情歌
(ii)HCQ is compatible with breastfeeding(LOE4,GOR D,SOA98.9%).
(iii)Men should not be discouraged from taking HCQ while trying to conceive(LOE2À,GOR D,SOA98.9%).Recommendations for MTX in pregnancy and breastfeeding
(i)MTX at any do should be avoided in pregnancy
and stopped3months in advance of conception (LOE2À,GOR D,SOA100%).
(ii)In women treated with low-do MTX within3 months prior to conception,folate supplementation (5mg/day)should be continued prior to and throughout pregnancy(LOE1,GOR B,SOA
98.4%).
(iii)In the ca of accidental pregnancy on low-do MTX,the drug should be stopped immediately, folate supplementation(5mg/day)continued and a careful evaluation of foetal risk carried out by local experts(LOE4,GOR D,SOA100%).
(iv)MTX cannot be recommended in breastfeeding be-cau of theoretical risks and insufficient outcome data(LOE4,GOR D,SOA100%).
(v)Bad on limited evidence,low-do MTX may be compatible with paternal exposure(LOE2+,GOR D,SOA95.8%).
Recommendations for SSZ in pregnancy and breastfeeding
(i)SSZ with folate supplementation(5mg/day)is com-
patible throughout pregnancy(LOE2+,GOR C, SOA100%).
(ii)SSZ is compatible with breastfeeding in healthy, full-term infants(LOE4,GOR D,SOA100%). (iii)Men taking SSZ may have reduced fertility.There is no evidence,however,that conception is enhanced by stopping SSZ for3months prior to conception unless conception is delayed>12months when other caus of infertility should also be considered (LOE3,GOR D,SOA97.4%). Recommendations for LEF in pregnancy and breastfeeding
四年级上册数学教案(i)Bad on limited evidence,LEF may not be a human
teratogen but it is still not recommended in women planning pregnancy(LOE2+,GOR C,SOA100%). (ii)Women on LEF considering pregnancy should stop and undergo cholestyramine washout before switching to alternative medication compatible with pregnancy(LOE2+,GOR C,SOA100%). (iii)There is no human evidence of incread congeni-tal abnormalities on LEF if washout is given.
Therefore,if accidental conception occurs on LEF, the drug should be stopped immediately and cho-l
estyramine washout given until plasma levels are undetectable(LOE2+,GOR C,SOA98.9%). (iv)No data exist on excretion into breast milk, therefore breastfeeding is not recommended(LOE 4,GOR D,SOA100%).
翻越那座山(v)Bad on very limited evidence,LEF may be com-patible with paternal exposure(LOE4,GOR D,SOA
98.9%).
Julia Flint et al.
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Recommendations for AZA in pregnancy and breastfeeding
(i)AZA is compatible throughout pregnancy at 42mg/kg/day (LOE 2++,GOR B,SOA 100%).
(ii)AZA is compatible with breastfeeding (LOE 2À,
GOR D,SOA 99.5%).
(iii)AZA is compatible with paternal exposure (LOE 2+,
GOR D,SOA 100%).
Recommendations for CSA in pregnancy and breastfeeding
(i)CSA is compatible throughout pregnancy at the lowest effective do (LOE 1,GOR B,SOA 100%).(ii)Mothers on CSA should not be discouraged from
breastfeeding (LOE 3,GOR D,SOA 100%).
(iii)Bad on limited evidence,CSA is compatible with pa-ternal exposure (LOE 2À,GOR D,SOA 98.9%).
Recommendations for tacrolimus in pregnancy and breastfeeding
(i)Tacrolimus is compatible throughout pregnancy at the lowest effective do (LOE 2À,GOR D,SOA 99.5%).
(ii)Mothers on tacrolimus should not be discour-aged from breastfeeding (LOE 3,GOR D,SOA 99.5%).
(iii)Bad on limited evidence,tacrolimus is compatible
with paternal exposure (LOE 2À,GOR D,SOA 98.4%).
Recommendations for CYC in pregnancy and breastfeeding
(i)CYC is teratogenic and gonadotoxic,therefore it should only be considered in pregnancy in life-/organ-threatening maternal dia (LOE 2,GOR C,SOA 100%).
T ABLE 1Summary of drug compatibility in pregnancy and breastfeeding
Corticosteroids Prednisolone
Yes Yes Yes Yes Yes Methylprednisolone Yes Yes Yes Yes Yes Antimalarials HCQ Yes
Yes Yes Yes Yes a DMARDs
MTX <20mg/week Stop 3months in advance No No No Yes a SSZ (with 5mg folic acid)Yes
Yes Yes Yes b
Yes c LEF
Cholestyramine washout,no No No No data Yes a AZA <2mg/kg/day Yes Yes Yes Yes yes CSA
Yes Yes d Yes d Yes a Yes a Tacrolimus Yes Yes d Yes d Yes a Yes a CYC No
No e No e No No MMF Stop 6weeks in advance No No No Yes a IVIG Yes Yes Yes
Yes Yes a Anti-TNF Infliximab Yes Yes Stop at 16weeks Yes a Yes a Etanercept Yes Yes Second but not third Yes a Yes a Adalimumab Yes Yes Second but not third Yes a Yes a
Certolizumab Yes Yes Yes a
Yes a
No data Golimumab No data No data No data No data No data Other biologics Rituximab Stop 6months in advance No f No No data Yes a Tocilizumab Stop 3months in advance No f No No data No data g Anakinra No No f No No data No data g Abatacept No No f No No data No data g Belimumab
No
No f
No
No data
No data g
For further information and caveats,e relevant recommendations and main text in executive summary and full guideline.a
Data are limited.b In healthy full-term infants only.c Conception may be enhanced by stopping SSZ for 3months prior to conception.d Suggested monitoring of maternal blood pressure,renal function,blood gluco and drug levels.e Only consider in vere or life-/organ-threatening maternal dia.f Unintentional first trimester exposure is unlikely to be harmful.g Unlikely to be harmful.
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding
by guest on January 12, 2016
(ii)There is no evidence to recommend the u of CYC in breastfeeding(LOE4,GOR D,SOA100%). (iii)Paternal exposure to CYC is not recommended (LOE4,GOR D,SOA98.4%). Recommendations for MMF in pregnancy and breastfeeding
近义词组成的词语(i)MMF remains contraindicated during pregnancy
(LOE2À,GOR D,SOA100%).
(ii)Treatment with MMF should be stopped at least6 weeks before a planned pregnancy(LOE3,GOR D, SOR100%).
(iii)No data exist on excretion into breast milk,there-fore breastfeeding is not recommended(LOE4, GOR D,SOA99.5%).
(iv)Bad on very limited evidence,MMF is compatible with paternal exposure(LOE2À,GOR D,SOA
98.9%).
Recommendations for IVIG in pregnancy and breastfeeding意大利语发音
(i)IVIG is compatible with pregnancy(LOE1++,GOR
A,SOA100%).
(ii)IVIG is compatible with breastfeeding(LOE4,GOR D,SOA98.9%).
(iii)Bad on maternal compatibility,IVIG is unlikely to be harmful(LOE4,GOR D,SOA98.9%). Recommendations for anti-TNF medications in pregnancy and breastfeeding
(i)Infliximab(IFX)may be continued until16weeks
and etanercept(ETA)and adalimumab(ADA)may be continued until the end of the cond trimester (LOE2À,GOR D,SOA98.9%).
(ii)To ensure low/no levels of drug in cord blood at delivery,ETA and ADA should be avoided in the third trimester and IFX stopped at16weeks.If the drugs are continued later in pregnancy to treat active dia,then live vaccines should be avoided in the infant until7months of age(LOE 3,GOR D,SOA98.9%).
(iii)Certolizumab pegol is compatible with all three tri-mesters of pregnancy and has reduced placental transfer compared with other TNF inhibitors (TNFis)(LOE2À,GOR D,SOA97.9%).
(iv)Golimumab is unlikely to be harmful in the first tri-mester(LOE4,GOR D,SOA97.9%)
(v)Women should not be discouraged from breast-feeding on TNFis,but caution is recommended until further information is available(LOE3,GOR D,SOA98.4%).
(vi)Bad on limited evidence IFX,ETA and ADA are compatible with paternal exposure(LOE2À,GOR D,SOA98.9%).Recommendations for rituximab(RTX)in pregnancy and breastfeeding
(i)RTX should be stopped6months before concep-
tion.Limited evidence has not shown RTX to be teratogenic and only cond-/third-trimester expos-ure is associated with neonatal B cell depletion.
Therefore,unintentional RTX exposure early in the first trimester is unlikely to be harmful(LOE2À, GOR D,SOA97.9%).
(ii)There are no data on RTX u in breastfeeding (SOA100%).
(iii)Bad on limited evidence,RTX is compatible with paternal exposure(LOE2À,GOR D,SOA98.4%). Recommendations for tocilizumab(TCZ) in pregnancy and breastfeeding
(i)TCZ should be stopped at least3months before
conception,but unintentional exposure early in the first trimester is unlikely to be harmful(LOE3,GOR D,SOA96.8%).
(ii)There are no data on TCZ u in breastfeeding (SOA99.5%).
(iii)There are no data relating to paternal exposure to TCZ,but it is unlikely to be harmful(LOE4,GOR D, SOA97.9%).
Recommendations for anakinra in preg-nancy and breastfeeding
(i)There is limited evidence on which to ba a rec-
ommendation for anakinra in pregnancy,but unin-tentional exposure in the first trimester is unlikely to be harmful(LOE2À,GOR D,SOA96.8%).
(ii)There are no data on anakinra u in breastfeeding (SOA100%).
(iii)There are no data relating to paternal exposure to anakinra,but it is unlikely to be harmful(LOE4, GOR D,SOA98.9%).
Recommendations for abatacept(ABA)in pregnancy and breastfeeding
(i)There are insufficient data to recommend ABA in
pregnancy.Unintentional exposure early in the first trimester is unlikely to be harmful(LOE3,GOR D, SOA98.9%).
(ii)There are no data on ABA u in breastfeeding (SOA100%).
(iii)There are no data relating to paternal exposure to ABA,but it is unlikely to be harmful(LOE4,GOR D, SOA98.9%).
Recommendations for belimumab(BEL) in pregnancy and breastfeeding
(i)There are insufficient data to recommend BEL in
pregnancy.Unintentional exposure early in the first
Julia Flint et al.
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trimester is unlikely to be harmful(LOE3,GOR D, SOA100%).
(ii)There are no data on BEL u in breastfeeding (SOA100%).
(iii)There are no data relating to paternal exposure to BEL,but it is unlikely to be harmful(LOE4,GOR D, SOA98.9%).
Funding:No specific funding was received from any fund-ing bodies in the public,commercial or not-for-profit c-tors to carry out the work described in this article. Disclosure statement:K.S.has received educational sup-port from Daiichi Sankyo.C.G.has undertaken consultan-cies and received honoraria from Bristol-Myers Squibb, GlaxoSmithKline,MedImmune,Merck Serono and UCB, has been a member of speakers’bureau for GlaxoSmithKline,UCB and Lilly and has received re-arch grant support from UCB,but none of the activ-ities have been related to the u of any specific drug in pregnancy.L.M.has received support from AbbVie and Pfizer to attend education meetings and received partici-pation honoraria from MSD.I.G.has received unit support from AbbVie,MSD,Roche,Bristol-Myers Squibb and Sobi,participated on advisory boards for Pfizer and received fees for participation in an educational meeting by UCB.D.W.has received financial support
for an inde-pendent PhD studentship from GlaxoSmithKline and Alere and acted as a consultant for Roche Diagnostics.M.N. has received unit and individual support to attend meet-ings from UCB and Jann UK and participated on an expert panel for UCB.M.K.has received individual support to attend meetings from GlaxoSmithKline,UCB and Astra-Zeneca,chairing fees from Bristol-Myers Squibb and honoraria from GlaxoSmithKline/Human Genome Sciences,Medimmune,INOVA Diagnostics and Merck.M.G.has received individual support to attend a meeting from Roche.All others have declared no conflicts of interest.
Supplementary data
The full guideline is available as supplementary data at Rheumatology Online.
References
1Østenn M,Andreoli L2,Brucato A et al.State of the art: reproduction and pregnancy in rheumatic dias.
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2Østenn M,Khamashta M,Lockshin M et al.Anti-inflammatory and immunosuppressive drugs and
reproduction.Arthritis Res Ther2006;8:209.
3Østenn M,Lockshin M,Doria A et al.Update on safety during pregnancy of biological agents and some im-
munosuppressive anti-rheumatic drugs.Rheumatology 2008;47:iii28 31.
4Flint J,Panchal S,Hurrell A et al.BSR and BHPR guideline on prescribing drugs in pregnancy and
breastfeeding—Part II:analgesics and other drugs ud in rheumatology practice.Rheumatology2016;55;
doi:10.1093/rheumatology/kev405.
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding
by guest on January 12, 2016
