Abstract
Methotrexate (MTX) is a frequently used anti-psoriatic drug that is commonly recommended in international psoriasis guidelines. It is effective in treating skin lesions, nail changes and psoriatic arthritis. In 2017 a prospective, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, commonly known as the METOP trial, was published assessing the effectiveness and safety of subcutaneous administration of methotrexate. Because trial data do not always relate to real-life data with unselected patient populations, we wanted to determine whether the data obtained in the METOP-trial correspond to real-life registry data from our Swiss Dermatology Network for Targeted Therapies (SDNTT). Data of 449 patients with moderate to severe psoriasis who participated in the SDNTT registry between 2011 and 1st of July 2017 were analyzed. Only patients receiving methotrexate s.c. were included. 66 patients under MTX were included into this study. Baseline PASI was 6.3 ± 3.8 (SDNTT) compared to 15.9 ± 5.9 in the METOP trial. In our cohort, only 18% of all patients reached PASI 75 after 12 weeks, 6% showed a complete remission (PASI 100) compared to 41% and 4% in the METOP trial after 16 weeks. 22.7% of all patients showed increased liver enzymes in either study and nausea was seen in 15% (SDNTT) versus 22% (METOP) of patients. No severe adverse events were observed in our cohort. Compared to the METOP-trial, the response rates seen our real-world cohort were distinctly lower.
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Introduction
Psoriasis is an inflammatory skin disease, which runs a chronic course and affects about 2% of the population in western countries [36]. The contribution of genetic as well as environmental factors plays an important part to the manifestation of psoriasis symptoms [4, 5]. In the last decades, increasing numbers of therapeutic options have been developed. While there is excellent evidence for new and costly therapies, few trials have investigated the effectiveness and safety of classical therapeutic agents. Methotrexate (MTX), a folate antagonist is, however, still the most frequently used anti-rheumatic agent [44, 52]. Its effectiveness in psoriasis is also well known for more than 50 years [32]. MTX is commonly recommended in international psoriasis guidelines [18, 27, 30]. While several studies have shown good effectiveness of MTX in psoriatic arthritis [12, 22, 49], no improvement of synovitis was found in a randomized placebo-controlled trial, raising the question whether it classifies as a disease-modifying psoriatic arthritis treatment [26]. In nail psoriasis, systemic [14, 15, 21, 39, 41] as well as intralesional MTX [19, 31, 42] has been reported to be efficient.
When MTX is administrated, it docks onto intracellular folate receptors [17]. MTX and its polyglutamated derivatives act as a folate analog, competitively inhibiting dihydrofolate reductase (DHRF) leading to a decreased synthesis of pyrimidine and purine which is followed by a reduction in T-cell-induced cytokine production [17]. MTX is also reported to affect the homocysteine metabolism [17]. Mitogen-induced immunoglobulin synthesis and proliferation of peripheral blood cells is impaired via reduction of polyamine synthesis [34]. MTX is thought to inhibit the function of the 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, which leads to increased extracellular adenosine levels resulting in downregulation of inflammatory signaling [17]. In mouse models, neutrophil function is inhibited via adenosine release [13]. Adenosine itself is reported to have anti-inflammatory properties [40]. Yet, in animal models, the adenosine mediated properties of MTX have not been confirmed [3, 47]. In mouse models, MTX was shown to produce a state of anergy, where T as well as B cells were unresponsive to stimuli [16, 25]. In addition the action spectrum of MTX could be broader than expected, as an affinity of MTX for other folate-dependent enzymes like thymidylate synthase, AICAR (5-amino-imidazol-4-carboxamide ribonucleotide transformylase) and AICARFT (AICAR formyltransferase) has been reported [9, 47, 50].
Due to this very broad activity, MTX can subtly influence also concomitant low-level inflammatory states that are associated with co-morbidities. Indeed, MTX may reduce the cardiovascular risk in psoriasis patients [1, 2, 11, 20, 23, 24, 37]. Especially, when psoriasis and other risk factors for cardiac disease existed, MTX therapy was associated with a lower risk of developing cardiac events [48]. So far, no influence on hemoglobin A1C and fasting glucose level was found [53].
Apart from the use as a single drug, MTX has found its use also in more complex treatment regiments for inflammatory conditions. MTX is often co-administered with biologic drugs, either to enhance their effect [7, 17] or to reduce immunogenicity decreasing the risk of auto-antibody formation or diminishing them [38]. It is even recommended to be used concomitantly with some biologicals [45, 46] in certain cases. With increasing therapeutic options concomitant treatment has become less common though.
Unfortunately, only few stringently controlled trials have been performed with this drug in psoriasis [29]. Only three trials evaluated oral MTX administration in a head-to-head comparison with modern biologics, namely with adalimumab [43], briakinumab [39] and infliximab [6]. On average, PASI 75 was reached in 39.9–42% in week 16 [6, 39].
Because MTX can be administered both orally and subcutaneously (SQ), some efforts have been made to investigate whether either route yields higher effectiveness and less side effects. Indeed, in a 6-month well-controlled trial comparing oral and SQ administration of MTX in rheumatoid arthritis clearly showed that the latter was of higher effectiveness and had a much better profile concerning side effects, especially nausea. In a prospective, randomized, controlled trial in patients with rheumatoid arthritis, SQ administration of MTX has been found significantly more effective than oral administration [8]. This has influenced our daily practice towards almost exclusively subcutaneous use of MTX in psoriasis.
Perhaps the most important study with MTX is the recently published METOP-trial, a 52-week, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluated SQ MTX in moderate-to-severe psoriasis [51].
In the METOP trial, the safety profile was not dose-dependent. Side effects included elevation of liver enzymes up 23% and leukopenia in up to 5% of all patients. Nausea was reported in 22% of all patients [51].
However, as in all controlled trials in psoriasis, we are well aware that they do not directly translate to the clinical reality that is based on unselected patient populations with all kinds of less uniform and foreseeable medical situations. Thus, we chose to use our registry data to investigate the real-life effectiveness of SQ MTX and compare the results to the METOP trial.
Methods
Patient recruitment into the Swiss Dermatology Network for Targeted
Psoriasis patients who started a new systemic therapy were included in the national non-interventional Psoriasis Registry “SDNTT” (Swiss Dermatology Network for Targeted Therapies, NCT01706692). The registry complies with a common consensus in the PsoNet network [33, 35]. It was harmonized with similar psoriasis registries. All participants sign an informed consent prior to participation. All data was collected in Swiss hospitals since 2011. Treatment decisions were based on evidence-based national and international guidelines [27, 33]. Baseline data has been previously published [10, 27]. Until 1st of June 2017 (database cut-off), 449 patients were included in SDNTT.
Inclusion/exclusion criteria for the SDNTT
Inclusion criteria included age > 18 years, clinically confirmed diagnosis of moderate to severe psoriasis, the ability to apprehend the questionnaires, being methotrexate-naïve and consent to participate in this study. Patients with incomplete data were excluded. Only patients receiving methotrexate were included in this study (Fig. 1). Prior treatment included UVB narrow band therapy (n = 30), fumaric acid esters (n = 3), cyclosporine (n = 3), PUVA-therapy (n = 3) and oral retinoids (n = 3). 24 patients had no prior systemic therapy before methotrexate. Concomitant topical treatment occurred in all patients.
Data acquisition
Patient characteristics like age, gender, disease severity (i.e., PASI, BSA, NAPSI) was obtained by physicians. Impairment of health-related quality of life was assessed using the patient reported Dermatology Life quality Index (DLQI). Whether the patients suffered from psoriatic arthritis was not analyzed. For this study we analyzed data obtained at week 0 and week 12. Adverse events were collected during each consultation.
Administration and dosage
In the majority of cases, patients received 7.5 mg in week 0. In week 1 10 mg and from then on 15 mg weekly. The route of administration was subcutaneous in all patients. 24 h after the injection, oral folic acid 5 mg was routinely given. Laboratory control was performed before start of therapy and for the first 3 months every 4 weeks.
Statistical analysis
After normality testing, the Mann–Whitney U test was used for statistical analysis.
Results
66 patients were included into this study. The mean age was 46.3, ranging from 19 to 80 years. 18 participants were women (27.3%). Most patients solely suffered from plaque psoriasis 53 (80.3%), 3 (4.5%) participants had a pustular palmoplantar psoriasis. A combination of the two types was seen in 2 (3.0%) patients. Only 1 (1.5%) patient suffered from inverse psoriasis, while 4 (6.1%) showed a combined phenotype of plaque psoriasis and inverse psoriasis. Guttate psoriasis was seen in only 1 (1.5%) patients, but 2 (3.0%) patients suffered from combined guttate and plaque psoriasis (Table 1).
At baseline (visit 1, week 0, day 0) the mean PASI was 6.3 ± 3.8 (0.9–24.5). After 12 weeks the mean PASI was reduced to 2.7 ± 2.3 (0–11.6). The majority of the patients showed improvement, which was less than PASI 50 (n = 24; 36.3%). Only a few experienced worsening of disease (n = 3; 4.5%) and four participants reached PASI 100 (6.1%). PASI 75 was reached by 12 (18.2%) of all patients. 46 (69.7%) of all patients reached a PASI ≤ 3, compared to 12 (18.2%) at baseline. Nail psoriasis improved from a mean NAPSI of 16.4–13.0. Additionally, life quality drastically increased and mean DLQI was reduced from 10.9 to 4.5. At baseline only 4 patients (6.9%) had a DLQI ≤ 1, while after 12 weeks this was observed in 25 (43.1%) patients (Table 1).
The most common adverse event was an elevation of the liver enzymes. 11% of patients newly developed liver transaminase levels above the upper limit. No leukopenia was reported in our cohort. No severe adverse events were recorded in this cohort over the given time (Table 1).
When analyzing patients’ preceding therapies, most frequently, UVB narrow band therapy (n = 30, 45.5%) had been performed prior to MTX treatment (Table 1).
Discussion
Despite the fact that MTX is a traditional drug, its effectiveness has only recently been shown in several randomized controlled trials [6, 28, 43]. Because trial data do not always correspond to real-life data with unselected patient populations, we wanted to determine whether the data obtained in the METOP-trial correspond to real-life registry data. Compared to the METOP-trial, the response rates seen our cohort were distinctly lower. Indeed, only 18% of all MTX-treated patients in our registry reached PASI 75. Several explanations contributed to this lower-than-expected effectiveness (Fig. 2).
For instance, in the METOP trial, patients had a PASI at baseline 15.9, compared to 6.3 in our trial. The lower average PASI levels correspond well to the real-life situation in Switzerland. Additionally, the trial lasted longer and the PASI 75 was evaluated at 16 weeks, instead of 12. Therefore, in the METOP trial, patients had more time to reach this threshold than in our analysis of the SDNTT registry. Lastly, all patients in our cohort used MTX 15 mg s.c. weekly and no dose-escalation had been performed. In the METOP trial, patients were allowed to administer a dose of 25 per week in comparison. Furthermore, our cohort was smaller than the METOP trial and no placebo-group existed. Additionally, our analysis stopped after 3 months, while the METOP trial continued until week 52. While in the METOP trial only plaque-type psoriasis patients were included, in our cohort different kinds of psoriasis types were included.
Additionally, these differences could explain for the lower number of adverse events reported in our real-life cohort. No case of major cardiovascular event, neoplasm or death was reported in our study, nor did we observe a case of neutropenia. In other studies, relevant drop-out rates were seen with MTX [51], which we did not observe in the 12 weeks of analysis. Another possible explanation is underreporting in real-world setting.
Taken together, MTX is a cost-effective and popular treatment among our patients, but real-world data does not show it to be a competitive treatment in contrast to newer drugs.
Almost 70% of all patients reached a PASI ≤ 3 and 43.1% a DLQI ≤ 1. From our experience, the majority of patients is satisfied when a PASI ≤ 3 is reached. This is in concordance with the DLQI scores seen (62% reached a DLQI ≤ 3).
Therefore, we will continue using methotrexate as a first-line treatment in patients with moderate to severe psoriasis due to good experience and high patient satisfaction. In terms of effectiveness, our study points out that the real-world PASI 75 might significantly differ from the PASI 75 measured in clinical trials. In fact, we believe that the term “real-world PASI 75” would give clinicians a better understanding of what therapeutic success can be expected in daily routine.
References
Ahlehoff O, Skov L, Gislason G, Gniadecki R, Iversen L, Bryld LE et al (2015) Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort. J Eur Acad Dermatol Venereol 29(6):1128–1134
Ahlehoff O, Skov L, Gislason G, Lindhardsen J, Kristensen SL, Iversen L et al (2013) Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study. J Intern Med 273(2):197–204
Andersson SE, Johansson LH, Lexmuller K, Ekstrom GM (2000) Anti-arthritic effect of methotrexate: is it really mediated by adenosine? Eur J Pharm Sci 9(4):333–343
Anzengruber F, Drach M, Maul JT, Kolios AG, Meier B, Navarini AA (2018) Therapy response was not altered by HLA-Cw6 status in psoriasis patients treated with secukinumab: a retrospective case series. J Eur Acad Dermatol Venereol 32(7):e274–e276
Anzengruber F, Ghosh A, Maul JT, Drach M, Navarini AA (2017) Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis. Psoriasis (Auckl) 8:7–11
Barker J, Hoffmann M, Wozel G, Ortonne JP, Zheng H, van Hoogstraten H et al (2011) Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1). Br J Dermatol 165(5):1109–1117
Bendtzen K (2011) Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 63(4):867–870
Braun J, Kastner P, Flaxenberg P, Wahrisch J, Hanke P, Demary W et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 58(1):73–81
Budzik GP, Colletti LM, Faltynek CR (2000) Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line. Life Sci 66(23):2297–2307
Carrascosa JM, Vilavella M, Garcia-Doval I, Carretero G, Vanaclocha F, Dauden E et al (2014) Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry. J Eur Acad Dermatol Venereol 28(7):907–914
Churton S, Brown L, Shin TM, Korman NJ (2014) Does treatment of psoriasis reduce the risk of cardiovascular disease? Drugs 74(2):169–182
Coates LC, Helliwell PS (2016) Methotrexate efficacy in the tight control in psoriatic arthritis study. J Rheumatol 43(2):356–361
Cronstein BN, Naime D, Ostad E (1993) The antiinflammatory mechanism of methotrexate Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 92(6):2675–2682
Crowley JJ, Weinberg JM, Wu JJ, Robertson AD, Van Voorhees AS, National Psoriasis F (2015) Treatment of nail psoriasis: best practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol 151(1):87–94
Demirsoy EO, Kiran R, Salman S, Caglayan C, Akturk AS, Bayramgurler D et al (2013) Effectiveness of systemic treatment agents on psoriatic nails: a comparative study. J Drugs Dermatol 12(9):1039–1043
Garman RD, Munroe K, Richards SM (2004) Methotrexate reduces antibody responses to recombinant human alpha-galactosidase A therapy in a mouse model of Fabry disease. Clin Exp Immunol 137(3):496–502
Gerards AH, de Lathouder S, de Groot ER, Dijkmans BA, Aarden LA (2003) Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology (Oxford) 42(10):1189–1196
Gisondi P, Altomare G, Ayala F, Bardazzi F, Bianchi L, Chiricozzi A et al (2017) Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol 31(5):774–790
Grover C, Daulatabad D, Singal A (2017) Role of nail bed methotrexate injections in isolated nail psoriasis: conventional drug via an unconventional route. Clin Exp Dermatol 42(4):420–423
Gulliver WP, Young HM, Bachelez H, Randell S, Gulliver S, Al-Mutairi N (2016) Psoriasis patients treated with biologics and methotrexate have a reduced rate of myocardial infarction: a collaborative analysis using international cohorts. J Cutan Med Surg 20(6):550–554
Gumusel M, Ozdemir M, Mevlitoglu I, Bodur S (2011) Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. J Eur Acad Dermatol Venereol 25(9):1080–1084
Helliwell PS, Taylor WJ, Group CS (2008) Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs—comparison of drugs and adverse reactions. J Rheumatol 35(3):472–476
Hu SC, Lan CE (2017) Psoriasis and cardiovascular comorbidities: focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci 18(10):2211
Hugh J, Van Voorhees AS, Nijhawan RI, Bagel J, Lebwohl M, Blauvelt A et al (2014) From the Medical Board of the National Psoriasis Foundation: the risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. J Am Acad Dermatol 70(1):168–177
Joseph A, Munroe K, Housman M, Garman R, Richards S (2008) Immune tolerance induction to enzyme-replacement therapy by co-administration of short-term, low-dose methotrexate in a murine Pompe disease model. Clin Exp Immunol 152(1):138–146
Kingsley GH, Kowalczyk A, Taylor H, Ibrahim F, Packham JC, McHugh NJ et al (2012) A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford) 51(8):1368–1377
Kolios AG, Yawalkar N, Anliker M, Boehncke WH, Borradori L, Conrad C et al (2016) Swiss S1 guidelines on the systemic treatment of psoriasis vulgaris. Dermatology 232(4):385–406
Malgarini RB, Pimpinella G (2012) Briakinumab versus methotrexate for psoriasis. N Engl J Med 366(4):379 (author reply 80)
Mason KJ, Williams S, Yiu ZZN, McElhone K, Ashcroft DM, Kleyn CE et al (2019) Persistence and effectiveness of nonbiologic systemic therapies for moderate-to-severe psoriasis in adults: a systematic review. Br J Dermatol. https://doi.org/10.1111/bjd.17625
Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB et al (2008) Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 58(5):826–850
Mokni S, Ameur K, Ghariani N, Sriha B, Belajouza C, Denguezli M et al (2018) A case of nail psoriasis successfully treated with intralesional methotrexate. Dermatol Ther (Heidelb). 8(4):647–651
Morgado-Carrasco D, Fusta-Novell X, Riera Monroig J, Mascaro Galy JM (2017) The METOP Study: further evidence for the use of subcutaneous methotrexate in psoriasis. Actas Dermosifiliogr 108(9):865–866
Nast A, Gisondi P, Ormerod AD, Saiag P, Smith C, Spuls PI et al (2015) European S3-guidelines on the systemic treatment of psoriasis vulgaris–update 2015–short version–EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol 29(12):2277–2294
Nesher G, Moore TL (1990) The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine. Arthritis Rheum 33(7):954–959
Nishida C, Ko GT, Kumanyika S (2010) Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr 64(1):2–5
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM, Identification, Management of P et al (2013) Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 133(2):377–385
Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS (2005) Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 52(2):262–267
Raychaudhuri SP, Raychaudhuri SK (2009) Biologics: target-specific treatment of systemic and cutaneous autoimmune diseases. Indian J Dermatol 54(2):100–109
Reich K, Langley RG, Papp KA, Ortonne JP, Unnebrink K, Kaul M et al (2011) A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med 365(17):1586–1596
Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156(9):3435–3442
Sanchez-Regana M, Sola-Ortigosa J, Alsina-Gibert M, Vidal-Fernandez M, Umbert-Millet P (2011) Nail psoriasis: a retrospective study on the effectiveness of systemic treatments (classical and biological therapy). J Eur Acad Dermatol Venereol 25(5):579–586
Saricaoglu H, Oz A, Turan H (2011) Nail psoriasis successfully treated with intralesional methotrexate: case report. Dermatology 222(1):5–7
Saurat JH, Langley RG, Reich K, Unnebrink K, Sasso EH, Kampman W (2011) Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study. Br J Dermatol 165(2):399–406
Shiroky JB, Neville C, Esdaile JM, Choquette D, Zummer M, Hazeltine M et al (1993) Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis Results of a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 36(6):795–803
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM et al (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64(5):625–639
Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73(3):492–509
Smolenska Z, Kaznowska Z, Zarowny D, Simmonds HA, Smolenski RT (1999) Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis. Rheumatology (Oxford) 38(10):997–1002
Su YS, Yu HS, Li WC, Ko YC, Chen GS, Wu CS et al (2013) Psoriasis as initiator or amplifier of the systemic inflammatory March: impact on development of severe vascular events and implications for treatment strategy. J Eur Acad Dermatol Venereol 27(7):876–883
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673
van Ede AE, Laan RF, Blom HJ, De Abreu RA, van de Putte LB (1998) Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 27(5):277–292
Warren RB, Mrowietz U, von Kiedrowski R, Niesmann J, Wilsmann-Theis D, Ghoreschi K et al (2017) An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389(10068):528–537
Weinblatt ME, Kaplan H, Germain BF, Block S, Solomon SD, Merriman RC et al (1994) Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. Arthritis Rheum 37(10):1492–1498
Wu JJ, Rowan CG, Bebchuk JD, Anthony MS (2015) No association between TNF inhibitor and methotrexate therapy versus methotrexate in changes in hemoglobin A1C and fasting glucose among psoriasis, psoriatic arthritis, and rheumatoid arthritis patients. J Drugs Dermatol 14(2):159–166
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Mathias Drach has no conflict of interest. Karolina Papageorgiou has no conflict of interest. Julia-Tatjana Maul is an employee of USZ and holds a “Filling the GAP” scholarship. Vahid Djamei has no conflict of interest. Nikhil Yawalkar has received honoraria for consulting and advisory board attendance from Abbvie, Almirall, Amgen, Celgene, Eli Lilly, Galderma, Gebro, Janssen, Leo, Novartis, MSD and Pfizer. Peter Häusermann has received honoraria for consulting and advisory board attendance from Abbvie, Almirall, Celgene, Eli Lilly, Galderma, Janssen, Leo and Novartis. Florian Anzengruber is an employee of the University Hospital Zurich. He has received honoraria from Abbvie, Celgene, Leo Pharma, Galderma, Eli Lilly, Almirall, Janssen—Cilag and Novartis, but has no financial interest, nor holds any shares of any pharmaceutical company. Alexander A. Navarini is on the advisory board of AbbVie, Pfizer, Novartis, Celgene, MSD, Galderma, Sanofi, Boehringer-Ingelheim, Lilly.
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Drach, M., Papageorgiou, K., Maul, JT. et al. Effectiveness of methotrexate in moderate to severe psoriasis patients: real-world registry data from the Swiss Dermatology Network for Targeted Therapies (SDNTT). Arch Dermatol Res 311, 753–760 (2019). https://doi.org/10.1007/s00403-019-01945-6
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DOI: https://doi.org/10.1007/s00403-019-01945-6