Restricted accessReview articleFirst published online 2010-12
A Review of the Efficacy and Safety of Combined Methotrexate and Ultraviolet B Phototherapy versus Ultraviolet B Phototherapy Alone in the Treatment of Psoriasis
Methotrexate (MTX) and ultraviolet light B (UVB) phototherapy are effective as single agents for psoriasis. By combining the two agents, it is proposed that the use of UVB-MTX can yield greater therapeutic efficacy than using MTX or UVB alone and limit the cumulative exposure of both UVB and MTX to the patient.
Objective
To review evidence on the clinical efficacy and safety of using combined UVB-MTX compared with using UVB alone.
Methods
We performed a PubMed search for studies involving the combination of UV therapy with MTX. The reported studies evaluate the clinical efficacy and safety of UVB-MTX therapy compared with UVB alone.
Results
Based on the studies we reviewed, combined UVB-MTX therapy is more effective than UVB alone in treating psoriasis. The mean cumulative MTX doses ranged from 112 to 196 mg, and no cases of MTX-related liver toxicity symptoms were reported in the three studies.
Discussion
Combination phototherapy involving UVB-MTX is more clinically effective than UVB alone for patients with plaque-type psoriasis. The current review is limited by the absence of studies comparing the efficacy of combined UVB-MTX therapy with MTX monotherapy. Combination UVB-MTX therapy appears to be safe and well tolerated.
JensenP., SkovL., ZachariaeC.Systemic combination treatment for psoriasis: a review. Acta Derm Venereol.2010; 90(4): 341–9.
2.
LebwohlM., MenterA., KooJ., FeldmanS.R.Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol.2004; 50(3): 416–30.
3.
BerendsM.A., SnoekJ., de JongE.M.Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Aliment Pharmacol Ther.2006; 24(5): 805–11.
4.
MathiesonP.W.Cyclosporin: nephro-protective as well as nephrotoxic?Clin Exp Immunol.2000; 121(2): 179–80.
5.
SteinK.R., PearceD.J., FeldmanS.R.Targeted UV therapy in the treatment of psoriasis. J Dermatolog Treat.2008; 19(3): 141–5.
6.
MoritaA., WerfelT., StegeH.Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy. J Exp Med.1997; 186(10): 1763–8.
7.
JeffesEWIII, McCulloughJ.L., PittelkowM.R.Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate. J Invest Dermatol.1995; 104(2): 183–8.
8.
CronsteinB.N., NaimeD., OstadE.The antiinflammatory effects of methotrexate are mediated by adenosine. Adv Exp Med Biol.1994; 370: 411–6.
9.
MorisonW.L., MomtazK., ParrishJ.A., FitzpatrickT.B.Combined methotrexate-PUVA therapy in the treatment of psoriasis. J Am Acad Dermatol.1982; 6(1): 46–51.
10.
SternR.S.Lymphoma risk in psoriasis: results of the PUVA follow-up study. Arch Dermatol.2006; 142(9): 1132–5.
11.
PaulB.S., MomtazK., SternR.S., ArndtK.A., ParrishJ.A.Combined methotrexate-ultraviolet B therapy in the treatment of psoriasis. J Am Acad Dermatol.1982; 7(6): 758–62.
12.
AsawanondaP., NateetongrungsakY.Methotrexate plus narrowband UVB phototherapy versus narrowband UVB phototherapy alone in the treatment of plaque-type psoriasis: a randomized, placebo-controlled study. J Am Acad Dermatol.2006; 54(6): 1013–8.
13.
MahajanR., KaurI., KanwarA.J.Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque-type psoriasis–a randomized single-blinded placebo-controlled study. J Eur Acad Dermatol Venereol.2010; 24(5): 595–600.
14.
RamsayC.A., SchwartzB.E., LowsonD., PappK., BolducA., GilbertM.Calcipotriol cream combined with twice weekly broad-band UVB phototherapy: a safe, effective and UVB-sparing antipsoriatric combination treatment. The Canadian Calcipotriol and UVB Study Group. Dermatology.2000; 200(1): 17–24.
15.
HeckerD., LebwohlM.Topical calcipotriene in combination with UVB phototherapy for psoriasis. Int J Dermatol.1997; 36(4): 302–3.
BehrensS., Grundmann-KollmannM., SchienerR., PeterR.U., KerscherM.Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel. J Am Acad Dermatol.2000; 42(3): 493–5.
18.
SwinehartJ.M., LoweN.J.UVABA therapy for psoriasis: efficacy with shortened treatment times with the combined use of coal tar, anthralin, and metal halide ultraviolet machines. J Am Acad Dermatol.1991; 24(4): 594–7.
19.
IestJ., BoerJ.Combined treatment of psoriasis with acitretin and UVB phototherapy compared with acitretin alone and UVB alone. Br J Dermatol.1989; 120(5): 665–70.
20.
LoweN.J., PrystowskyJ.H., BourgetT., EdelsteinJ., NychayS., ArmstrongR.Acitretin plus UVB therapy for psoriasis: comparisons with placebo plus UVB and acitretin alone. J Am Acad Dermatol.1991; 24(4): 591–4.
MollerH.Methotrexate and the ultraviolet light inflammation in the guinea pig. Dermatologica.1970; 140(4): 225–30.
23.
KorossyK.S., HoodA.F.Methotrexate reactivation of sunburn reaction. Arch Dermatol.1981; 117(5): 310–11.
24.
SauratJ.H., StinglG., DubertretL.Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol.2008; 158(3): 558–66.
25.
BatchelorJ.M., IngramJ.R., WilliamsH.Adalimumab vs methotrexate for the treatment of chronic plaque psoriasis. Arch Dermatol.2009; 145(6): 704–6; discussion 706.
26.
RanjanN., SharmaN.L., ShankerV., MahajanV.K., TegtaG.R.Methotrexate versus hydroxycarbamide (hydroxyurea) as a weekly dose to treat moderate-to-severe chronic plaque psoriasis: a comparative study. J Dermatolog Treat.2007; 18(5): 295–300.
27.
BoffaM.J., ChalmersR.J., HaboubiN.Y., ShomafM., MitchellD.M.Sequential liver biopsies during long-term methotrexate treatment for psoriasis: a reappraisal. Br J Dermatol. 995; 133(5): 774–8.
28.
JaskiewiczK., VoigtH., BlakolmerK.Increased matrix proteins, collagen and transforming growth factor are early markers of hepatotoxicity in patients on long-term methotrexate therapy. J Toxicol Clin Toxicol.1996; 34(3): 301–5.
29.
LanseS.B., ArnoldG.L., GowansJ.D., KaplanM.M.Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis: an acceptable risk/benefit ratio. Dig Dis Sci.1985; 30(2): 104–9.
30.
EspinozaL.R., ZakraouiL., EspinozaC.G.Psoriatic arthritis: clinical response and side effects to methotrexate therapy. J Rheumatol.1992; 19(6): 872–7.
31.
HeydendaelV.M., SpulsP.I., OpmeerB.C.Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med.2003; 349(7): 658–65.
32.
CollinB., VaniA., OgboliM., MossC.Methotrexate treatment in 13 children with severe plaque psoriasis. Clin Exp Dermatol.2009; 34(3): 295–8.
33.
DahlM.G., GregoryM.M., ScheuerP.J.Liver damage due to methotrexate in patients with psoriasis. BMJ.1971; 1(5750): 625–30.
34.
TobiasH., AuerbachR.Hepatotoxicity of long-term methotrexate therapy for psoriasis. Arch Intern Med.1973; 132(3): 391–6.
35.
Van Dooren-GreebeR.J., KuijpersA.L., MulderJ., De BooT., Van de KerkhofP.C.Methotrexate revisited: effects of long-term treatment in psoriasis. Br J Dermatol.1994; 130(2): 204–10.
36.
SternR.S., LairdN.The carcinogenic risk of treatments for severe psoriasis. Photochemotherapy Follow-up Study. Cancer.1994; 73(11): 2759–64.
37.
FitzsimonsC.P., LongJ., MacKieR.M.Synergistic carcinogenic potential of methotrexate and PUVA in psoriasis. Lancet.1983; 1(8318): 235–6.
38.
LebwohlM., AliS.Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol.2001; 45(5): 649–61; quiz 662–4.
39.
SternR.S., KleinermanR.A., ParrishJ.A., FitzpatrickT.B., BleichH.L.Phototoxic reactions to photoactive drugs in patients treated with PUVA. Arch Dermatol.1980; 116(11): 1269–71.
40.
SternR.S.Photocarcinogenicity of drugs. Toxicol Lett.1998; 102–3: 389–92.
41.
SardasS., KarahalilB., KarakayaA.E., SasmazR.Mutagenic risk in psoriatic patients before and after 8-methoxypsoralen and long-wave ultraviolet radiation. Mutat Res.1994; 312(2): 79–83.
42.
WeischerM., BlumA., EberhardF., RockenM., BerneburgM.No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study. Acta Derm Venereol.2004; 84(5): 370–4.
43.
Pasker-de JongP.C., WielinkG., van der ValkP.G., van der WiltG.J.Treatment with UV-B for psoriasis and nonmelanoma skin cancer: a systematic review of the literature. Arch Dermatol.1999; 135(7): 834–40.
44.
LeeE., KooJ., BergerT.UVB phototherapy and skin cancer risk: a review of the literature. Int J Dermatol.2005; 44(5): 355–60.
45.
NaldiL.Malignancy concerns with psoriasis treatments using phototherapy, methotrexate, cyclosporin, and biologics: facts and controversies. Clin Dermatol.2010; 28(1): 88–92.
46.
SternR.S., LangeR.Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment. J Invest Dermatol.1988; 91(2): 120–4.
47.
SternR.S.Malignant melanoma in patients treated for psoriasis with PUVA. Photodermatol Photoimmunol Photomed.1999; 15(1): 37–8.
