The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.
LevyJ.Double-blind controlled evaluation of azathioprine treatment in rheumatoid arthritis and psoriatic arthritis. Arthritis Rheum1972; 15: 116–7.
2.
Cooperating Clinics Committee of the American Rheumatism Association. A controlled trial of cyclophosphamide in rheumatoid arthritis. N Engl J Med1970; 283: 883–9.
3.
AnastassiadesTP, Remission-inducing drugs in rheumatoid arthritis. Can Med Assoc J1980; 122: 405–15.
4.
LidskyMDSharpJTBillingsS.CurtisJEHershEM, Double-blind study of cyclophosphamide in rheumatoid arthritis (RA) (abstract). Arthritis Rheum1972; 15: 117.
5.
WilliamsHJReadingJCWardJRO'brienWM, Comparison of high and low dose cyclophosphamide therapy in rheumatoid arthritis. Arthritis Rheum1980; 23: 521–7.
6.
WilkeWSCalabreseLMScherbelAL, Methotrexate in the treatment of rheumatoid arthritis. Cleve Clin Q1980; 47: 305–9.
7.
SteinbergADPlotzPHWolffSM., Cytotoxic drugs in treatment of non-malignant diseases. Ann Intern Med1972; 76: 619–42.
8.
ScheinPSWinokurSH, Immunosuppressive and cytotoxic chemotherapy: Long-term complications. Ann Intern Med1975; 82: 84–95.
9.
O'brienWMVan ScottEJBlackRLEisenAZBunimJJ, Clinical trial of amethopterin (methotrexate) in psoriatic and rheumatoid arthritis (preliminary report). Arthritis Rheum1962; 5: 312.
10.
KaplanSRCalabresiP.Immunosuppressive agents. New Engl J Med1973; 289: 1234–6.
11.
ClineMJHaskellCM, Cancer chemotherapy. Cancer chemotherapy: W.B. Saunders, 1980: 1–12.
12.
DorrRTFritzWL, Cancer chemotherapy handbook. Cancer chemotherapy handbook: Elsevier North Holland Inc.1980: 3–9.
13.
CalabresiP.ParksRE, Antiproliferative agents and drugs used for immunosuppression. In: GoodmanLSGilmanAGGilmanA., eds. The pharmacological basis of therapeutics. 6th ed.New York: Macmillan, 1980: 1272–6.
14.
SteinbergAD, An approach to the use of immunosuppressive drugs in nonmalignant diseases. J Allergy Clin Immunol1973; 52: 242–50.
15.
BleyerWA, The clinical pharmacology of methotrexate. Cancer1978; 41: 36–51.
16.
HershEMWongVGFreireichEJ, Inhibition of local inflammatory response in man by antimetabolites. Blood1966; 27: 38–48.
17.
ThomasEDStorbR.The effect of amethopterin on the immune response. Ann NY Acad Sci1971; 186: 467–74.
18.
HurdE.Immunosuppressive and antiinflammatory properties of cyclophosphamide, azathioprine and methotrexate. Arthritis Rheum1973; 16: 84–8.
19.
StevensJEWilloughbyDA, The anti-inflammatory effect of some immunosuppressive agents. J Pathol1969; 97: 367–73.
20.
TsukadaW.AkimotoT.MizushimaY.Some aspects of antiinflammatory action of immunosuppressive drugs. Jpn J Pharmacol1974; 24: 583–8.
21.
GubnerRSAugustVEGinsbergV.Therapeutic suppression of tissue reactivity: II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci1951; 221: 176–82.
22.
KersleyGD, Amethopterin (methotrexate) in connective tissue diseases—psoriasis and polyarthritis. Ann Rheum Dis1968; 27: 64–6.
23.
VoglerWR, Treatment of rheumatoid arthritis with amethopterin (methotrexate) (abstract). Clin Res1970; 18: 46.
MarksJSStewartIMHunterJaa.Intra-articular methotrexate in rheumatoid arthritis. Lancet1976; 2: 857–8.
26.
BirdHARingEFJDanielR.BaconPA, Comparison of intraarticular methotrexate with intra-articular triamcinolone hex-acetonide by thermography. Curr Med Res Opin1977; 5: 141–6.
27.
HallGHJonesBJMHeadACJonesVE, Intraarticular methotrexate. Clinical and laboratory study in rheumatoid and psoriatic arthritis. Ann Rheum Dis1978; 37: 351–6.
28.
WiggintonSMChuBCFWeismanMHHowellSB, Methotrexate pharmacokinetics after intra-articular injection in patients with rheumatoid arthritis. Arthritis Rheum1980; 23: 119–22.
29.
WeinsteinGDFrostP.Methotrexate for psoriasis: A new therapeutic schedule. Arch Dermatol1971; 103: 33–8.
MichaelsRMNashelDJLeonardA.SliwinskiAJDerbesSJ, Weekly intravenous methotrexate in the treatment of rheumatoid arthritis. Arthritis Rheum1982; 25: 339–41.
HoffmeisterRT, Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med1983; 75: 69–73.
36.
SteinssonK.WeinsteinA.KornJ.AbelesM.Low dose methotrexate in rheumatoid arthritis. J Rheumatol1982; 9: 860–6.
37.
GroffGDShenbergerKNWilkeWSTaylorTH, Low dose oral methotrexate in rheumatoid arthritis: An uncontrolled study and review of the literature. Semin Arthritis Rheum1983; 12: 333–47.
AndersonPAWestSGClaypoolRCO'dellJ.Kotzin bl, via cs. Pulse methotrexate therapy for rheumatoid arthritis: A double-blind crossover study. Arthritis Rheum1984; 27 (suppl): S25.
40.
RussellASWattsC.ThompsonR., A double-blind placebo controlled short-term trial of parenteral methotrexate in rheumatoid arthritis. Arthritis Rheum1984; 27 (suppl): S59.
41.
McKendryR.HamdyH.MierinsE.Azathioprine compared with methotrexate in the treatment of rheumatoid arthritis—results of a double-blind 24 week trial. Arthritis Rheum1984; 27 (suppl): S57.
42.
WardJR. The Cooperative Systematic Studies of Rheumatic Diseases. A prospective randomized controlled trial of low dose pulse methotrexate in rheumatoid arthritis. Arthritis Rheum1984; 27 (suppl): S40.
43.
FitzgeraldO.HanlyJ.MolonyJ.BresnihanB.Poor long term results from low dose methotrexate therapy in rheumatoid arthritis. Arthritis Rheum1984; 27: 599–600.
44.
Freeman-NarrodM.GerstleyBJEngstromPFBornsteinRS, Comparison of serum concentrations of methotrexate after various routes of administration. Cancer1975; 36: 1619–24.
45.
ShenDDAzarnoffDL, Clinical pharmacokinetics of methotrexate. Drugs1978; 3: 1–13.
WilkeWSCalabreseLHSegalAM, Incidence of untoward reactions in patients with rheumatoid arthritis treated with methotrexate. Arthritis Rheum1983; 26 (suppl): S56.
48.
PerruquetJLHarringtonTMDavisDE. Pneumocystis carinii pneumonia following methotrexate therapy for rheumatoid arthritis. Arthritis Rheum1983; 26: 1291–2.
49.
Del PaineDWLeekJCJackleC.RobbinsDL, Gynecomastia associated with low dose methotrexate therapy. Arthritis Rheum1983; 26: 691–2.
50.
SussmanA.LeonardJM, Psoriasis, methotrexate and oligospermia. Arch Dermatol1980; 116: 215–7.
51.
NyforsA.Benefits and adverse drug experiences during long-term methotrexate treatment of 248 psoriatics. Dan Med Bull1978; 25: 208–11.
52.
El-BeheirgA.El-MansyE.KanelN., Methotrexate and fertility in men (letter). Arch Androl1979; 3: 177.
53.
DahlGCGregoryMMScheuerPJ, Liver damage due to methotrexate in patients with psoriasis. Br Med J1971; 1: 625–9.
54.
DahlGCGregoryMMScheuerPJ, Methotrexate hepatotoxicity in psoriasis—comparison of different dose regimens. Br Med J1972; 1: 654–6.
GowansJDCArnoldG.KaplanM.WilgramG.ChangLW, Long term therapy of psoriactic and rheumatoid arthritis with oral methotrexate monitored by serial liver biopsies. Arthritis Rheum1979; 22: 615–6.
57.
RoenigkHHAuerbachR.MaibachHIWeinsteinGD, Methotrexate guidelines revised. J Am Acad Dermatol1982; 6: 145–55.
58.
BailinPLTindallJPRoenigkHHJrHogarMD, Is methotrexate therapy for psoriasis carcinogenic?JAMA1975; 232: 359–62.
59.
CannonGWWardJRCleggDOSamuelsonCOJrAbbottTM, Acute lung disease associated with low dose pulse methotrexate therapy in patients with rheumatoid arthritis. Arthritis Rheum1983; 26: 1269–74.
60.
YoungP.RardinT.Jr.Problems of methotrexate administration (abstract). Arthritis Rheum1972; 15: 463.
61.
EngelbrechtJACalhoonSLScherrerJL, Methotrexate pneumonitis after low dose therapy for rheumatoid arthritis. Arthritis Rheum1983; 26: 1275–8.
62.
SchwartzKRKajaniMK, Methotrexate therapy and pulmonary disease. JAMA1969; 207: 923–8.
63.
GoldmanGCMoschellaSL, Severe pneumonitis during methotrexate therapy. Arch Dermatol1971; 103: 194–7.
64.
LieglerDGHendersonESHahnMAOliverioVT, The effect of organic acids on the renal clearance of methotrexate in man. Clin Pharmacol Ther1969; 10: 849–57.
65.
StollerRGJacobsSADrakeJCLutzRJFreiE.Pharmacokinetics of high dose methotrexate (NSC-740). Cancer Chemother Rep1975; 6: 19–24.
