HomeNon classéTraitement de la Polyarthrite rhumatoïde (PR) par le méthotrexate (MTX)

Traitement de la Polyarthrite rhumatoïde (PR) par le méthotrexate (MTX)

Publié le

spot_img

Arthri­tis Rheum. 2008 Nov;58(11):3299–308

Trai­te­ment de la PR par MTX : démar­rer à dose éle­vée pour une effi­ca­ci­té plus rapide ?

Le métho­trexate consti­tue aujourd’­hui le trai­te­ment de fond de réfé­rence de la poly­ar­thrite rhu­ma­toïde. Autre­fois débu­té à la dose moyenne de 7,5 mg/semaine , on consi­dère aujourd’­hui qu’il est pré­fé­rable de débu­ter à une dose plus éle­vée de l’ordre de 10 voire 15 mg/semaine.

Phar­ma­co­ki­ne­tics of oral metho­trexate in patients with rheu­ma­toid arthritis.
Dal­rymple JM, Stamp LK, O’Don­nell JL, Chap­man PT, Zhang M, Bar­clay ML.
Uni­ver­si­ty of Ota­go, Christ­church, New Zealand.

OBJECTIVE : There is evi­dence sup­por­ting a the­ra­peu­tic range for metho­trexate poly­glu­ta­mate (MTX­Glu) concen­tra­tions in the treat­ment of rheu­ma­toid arthri­tis (RA). Know­ledge of the phar­ma­co­ki­ne­tics of MTXGlu1‑5 is requi­red for opti­mal timing of blood sam­pling. The aim of this stu­dy was to deter­mine the time to stea­dy state and the half-life of accu­mu­la­tion of red blood cell (RBC) MTXGlu1‑5 in patients with RA com­men­cing oral MTX, and the time for RBC MTXGlu1‑5 to become unde­tec­table and the half-life of eli­mi­na­tion of RBC MTXGlu1‑5 in patients cea­sing treat­ment with oral MTX.

METHODS : Ten patients begin­ning treat­ment and 10 patients stop­ping treat­ment with low-dose oral MTX were recrui­ted. Blood samples were ini­tial­ly col­lec­ted week­ly, with gra­dual exten­sion to month­ly col­lec­tion over the stu­dy per­iod. RBC MTXGlu1‑5 concen­tra­tions were assayed by high-per­for­mance liquid chro­ma­to­gra­phy. Results were ana­ly­zed using a first-order expo­nen­tial method.

RESULTS : The median times to reach stea­dy state in RBCs (defi­ned as 90% of the maxi­mum concen­tra­tion) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, res­pec­ti­ve­ly, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of accu­mu­la­tion for RBC MTXGlu1‑5 ran­ged from 1.9 weeks to 45.2 weeks. The median times for MTX­Glus to become unde­tec­table in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, res­pec­ti­ve­ly, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of eli­mi­na­tion for RBC MTXGlu1‑5 ran­ged from 1.2 weeks to 4.3 weeks.

CONCLUSION : There is wide inter­pa­tient varia­bi­li­ty of RBC MTXGlu1‑5 accu­mu­la­tion and eli­mi­na­tion in adults with RA. These data also sug­gest that after a dose change, >6 months are requi­red for RBC MTXGlu1‑5 to reach stea­dy state. Such delays in achie­ving stea­dy state sug­gest that more rapid dose esca­la­tion or sub­cu­ta­neous admi­nis­tra­tion from the out­set should be considered.

==============================
 

Opti­mal dosage and route of admi­nis­tra­tion of methotrexate
in rheu­ma­toid arthri­tis : a sys­te­ma­tic review of the literature.

Vis­ser K, van der Hei­jde D.
Ann Rheum Dis. 2009 Jul;68(7):1094–9. Epub 2008 Nov 25.Click here to read Click here to read Links Depart­ment of Rheu­ma­to­lo­gy, Lei­den Uni­ver­si­ty Medi­cal Cen­ter, Lei­den, The Nether­lands. K.Visser@lumc.nl
Au total, l’é­tude conclut sur une pro­po­si­tion de poso­lo­gie de départ de 10 à 15 mg/s avec aug­men­ta­tion par palier de 5 mg toutes les 2 à 4 semaines jusqu’à obten­tion d’une dose de 20 à 30 mg/s en fonc­tion de la réponse cli­nique et de la tolé­rance ; la voie d’administration paren­té­rale pour­rait être envi­sa­gée en cas de réponse cli­nique insuf­fi­sante ou d’intolérance.


OBJECTIVES : To review sys­te­ma­ti­cal­ly the avai­lable lite­ra­ture on the opti­mal dosage and route of admi­nis­tra­tion of metho­trexate in patients with rheu­ma­toid arthri­tis (RA), as an evi­dence base for gene­ra­ting cli­ni­cal prac­tice recommendations.

METHODS : A sys­te­ma­tic lite­ra­ture search was car­ried out in MEDLINE, EMBASE, Cochrane Libra­ry and Ame­ri­can Col­lege of Rheumatology/European League Against Rheu­ma­tism mee­ting abs­tracts, sear­ching for ran­do­mi­sed control­led trials eva­lua­ting various dosages or routes of admi­nis­tra­tion of metho­trexate in RA. Articles that ful­filled pre­de­fi­ned inclu­sion cri­te­ria were sys­te­ma­ti­cal­ly revie­wed and the qua­li­ty was apprai­sed. Effect sizes and odds ratios for cli­ni­cal, radio­lo­gi­cal and toxi­ci­ty out­comes were cal­cu­la­ted and direct­ly or indi­rect­ly com­pa­red bet­ween stu­dy groups using metho­trexate in dif­ferent dosages or by dif­ferent routes.

RESULTS : A total of 38 publi­ca­tions out of 1748 iden­ti­fied refe­rences was inclu­ded in the review. Start doses of 25 mg/week or fast esca­la­tion with 5 mg/month to 25–30 mg/week were asso­cia­ted with higher cli­ni­cal effect sizes and more (gas­troin­tes­ti­nal) adverse events in com­pa­ri­son with doses of 5–15 mg/week or slow esca­la­tion. Star­ting with 15 mg/week sub­cu­ta­neous ver­sus oral metho­trexate was asso­cia­ted with higher cli­ni­cal effi­ca­cy but more with­dra­wal due to toxi­ci­ty in ear­ly RA. In long­stan­ding RA, after fai­lure on 15–20 mg/week oral­ly, a switch to 15 mg/week intra­mus­cu­lar­ly with sub­sequent dose esca­la­tion did not result in increa­sed efficacy.

CONCLUSIONS : Star­ting on metho­trexate 15 mg/week oral­ly, esca­la­ting with 5 mg/month to 25–30 mg/week, or the highest tole­rable dose, with a sub­sequent switch to sub­cu­ta­neous admi­nis­tra­tion in the case of an insuf­fi­cient res­ponse, seems to be the opti­mal evi­dence-based dosing and rou­ting recom­men­da­tion for metho­trexate in RA.

A une poso­lo­gie moyenne de 10,5 mg/s pour une durée moyenne de trai­te­ment de 55,8 mois, 20,2% des patients pré­sentent au moins un épi­sode d’augmentation des trans­ami­nases. La sur­ve­nue d’une cyto­lyse hépa­tique consti­tue 3,7% de causes d’arrêt. Une méta-ana­lyse avec biop­sies hépa­tiques répé­tées a sug­gé­ré une fré­quence des fibroses sévères ou cir­rhoses de l’ordre de 3%..


OBJECTIVE : To per­form a sys­te­ma­tic lite­ra­ture review of the long-term safe­ty of metho­trexate (MTX) mono­the­ra­py in rheu­ma­toid arthri­tis (RA).

METHODS : A search was per­for­med in Med­line, Cochrane and EMBASE. Adults with RA who had recei­ved MTX mono­the­ra­py for more than 2 years were studied.

RESULTS : 88 publi­shed stu­dies were inclu­ded. Over 12 years of treat­ment, the ter­mi­na­tion rate of MTX due to toxi­ci­ty was less than for sul­fa­sa­la­zine, gold, d‑penicillamine and higher than for hydroxy­chlo­ro­quine (level of evi­dence 2a-2b). Long-term use of MTX does not appear to be a risk fac­tor for serious infec­tions, inclu­ding herpes zos­ter (2b‑4), and could pro­vide a sur­vi­val bene­fit by redu­cing car­dio­vas­cu­lar mor­ta­li­ty (2b). The pre­va­lence of rai­sed liver enzymes (more than twice the upper limit of nor­mal) is close to 13% of patients ; 3.7% of patients stop­ped MTX per­ma­nent­ly owing to liver toxi­ci­ty (2b). Data on the risk for liver fibrosis/cirrhosis are conflic­ting : a meta-ana­ly­sis sho­wed an inci­dence of fibro­sis of 2.7% after 4 years of MTX (2a). Howe­ver, two other stu­dies on sequen­tial liver biop­sies did not show evi­dence for deve­lo­ping severe damage (2b). Insuf­fi­cient data are avai­lable to ful­ly assess the risk of lym­pho­ma and mali­gnan­cies, although there is no strong evi­dence of increa­sed risk (2b‑4).

CONCLUSION : This sys­te­ma­tic lite­ra­ture search on MTX mono­the­ra­py with rela­ti­ve­ly low-dose use during at least 2 years shows favou­rable long-term safety.

Revoir le métho­trexate

Derniers articles

Mycoplasma pneumoniae : maladies caractéristiques, traitements

Les maladies infectieuses constituent un problème de santé majeur et figurent parmi les dix...

Paralysie faciale a frigore : causes, symptômes, diagnostic et traitement

La paralysie faciale a frigore (PFF) est l’une des formes les plus fréquentes des...

Ostéopénie : clinique, physiopathologie, étiologies, traitement

L’ostéopénie est un état de fragilité osseuse fréquent à partir de 50 ans. Elle est...

L’OTITE SERO-MUQUEUSE DE L’ENFANT : Causes, Diagnostic et Traitements

Tout comme l’otite moyenne aiguë, l’otite séromuqueuse est une affection que l’on retrouve couramment...

Pour aller plus loin

Mycoplasma pneumoniae : maladies caractéristiques, traitements

Les maladies infectieuses constituent un problème de santé majeur et figurent parmi les dix...

Paralysie faciale a frigore : causes, symptômes, diagnostic et traitement

La paralysie faciale a frigore (PFF) est l’une des formes les plus fréquentes des...

Ostéopénie : clinique, physiopathologie, étiologies, traitement

L’ostéopénie est un état de fragilité osseuse fréquent à partir de 50 ans. Elle est...