Dear Sir,

We have read with great interest the letter by Dr. Silva and Dr. Santana published in the Journal of Crohn's and Colitis.1 They correctly point out that the wash-out for methotrexate (MTX) proposed in the Second ECCO Consensus on the diagnosis and management of Crohn's disease was short.2 In the dedicated European Consensus guidance on reproduction published in JCC in 20103 a wash out period of 3 to 6 months has been proposed. This interval is intended to clear all MTX from the body before conception and is undoubtedly an optimal algorithm to prevent peri-conceptual exposure. Most solid data on the teratogenicity of MTX stem from animal studies or from the use as a treatment in women with ectopic pregnancy.4 In these instances, MTX was given intentionally post-conception at much higher doses than the maintenance dose for Crohn's disease. The data from exposure to MTX in patients with rheumatoid disorders or IBD are scarce and limited to small case series or surveys. A minimal peri-conceptual treatment dose of 10 mg/wk has been invoked as the threshold for teratogenicity.5 Even with a 6 week wash out period, serum and tissue levels will be much lower than what is obtained with stable 10 mg/wk doses. Therefore, the proposed pre-conceptual 3 to 6 month wash out period for MTX is preferred, but the evidence to support this long wash out is not overwhelming.

Conflict of interest

None.

References

1
Silva
B.C.
Santana
G.O.
Methotrexate suspension before pregnancy
J Crohns Colitis
 
7
2013
151
2
Van Assche
G.
Dignass
A.
Reinisch
W.
van der Woude
C.J.
Sturm
A.
De Vos
M.
et al
The second European evidence-based consensus on the diagnosis and management of Crohn's disease. Special situations
J Crohns Colitis
 
4
2010
63
101
3
van der Woude
C.J.
Kolacek
S.
Dotan
I.
Oresland
T.
Vermeire
S.
Munkholm
P.
et al
European evidence-based consensus on reproduction in inflammatory bowel disease
J Crohns Colitis
 
4
2010
493
510
4
Hyoun
S.C.
Obican
S.G.
Scialli
A.R.
Teratogen update: methotrexate
Birth Defects Res
 
94
2012
187
207
5
Feldkamp
M.
Carey
J.C.
Clinical teratology counselling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy
Teratology
 
47
1993
533
539