Table 5. Summary of Systemic Drugs for Psoriasis Using Strength of Recommendation Taxonomy (SORT)4
DrugMechanism of ActionDosingFDA-Approved IndicationSORT LevelLevel of EvidenceStudies
    EtanerceptSoluble dimeric fusion protein that links the p75 TNF-α receptor to the Fc portion of IgG1, decreasing its activity33SC injection of 50 mg twice/week for 3 months, followed by 50 mg weekly33Moderate to severe plaque psoriasis and PsA36A1Amgen-Pfizer has >3 years of clinical data for this drug; early studies for rheumatoid arthritis have shown that 25 mg SC twice/week over 2 years not only has good clinical responses but also provides better mental health and less bone damage.37 This response reverted to baseline once etanercept was discontinued and improved when use of the drug resumed.37 Later, as these studies were conducted in patient cohorts with PsA and psoriasis, similar positive results were found: psoriatic skin plaques improved, structural damage halted, and inflammatory markers decreased, and the patients reported feeling better both physically and mentally.37
    AdalimumabRecombinant human Ig monoclonal antibody neutralizes the biological function of TNF-α by blocking its interaction with the p55 and p75 cell-surface TNF-α receptors38SC injection at a dosage of 80 mg at week 0, followed by 40 mg every 2 weeks beginning at week 233Moderate to severe plaque psoriasis and PsAA1Three major trials assessed the efficacy of adalimumab.39 After week 16 in each of these trials, approximately 80% of patients experienced a PASI 75* response.39
    InfliximabChimeric monoclonal antibody (75% human, 25% murine) in which the Fc portion is human IgG1 and the Fab portion is primarily of murine origin.40 Neutralizes soluble TNF-α and blocks membrane TNF-α.41The drug is administered intravenously every 8 weeks following an initial loading doseModerate to severe psoriasis
PsA (Preg Cat B)
A1Three major trials assessed efficacy of infliximab.4244 After maintenance phase (through week 50). patients remained at PASI 75.
Anti-infliximab antibodies commonly develop after prolonged therapy and can result in decreased drug efficacy or in some cases a severe infusion reaction with respiratory compromise.45
    UstekinumabHuman monoclonal antibody that blocks IL-12 and IL-23, binding the p40 subunit, which activates T cells in psoriasis.745 mg for patients weighing ≤100 kg; 90 mg for patients weighing >100 kg33
SC at weeks 0 and 4, repeated every 12 weeks33
Moderate to severe plaque psoriasisA1Two phase III clinical trials showing that about two-thirds of patients achieved a PASI 75 response after 12 weeks of treatment.46,47*
    AcitretinOral retinoid inhibits induction of helper T lymphocytes via IL-6 by modulating gene expression,33 which functions to regulate the keratinocyte turnover in psoriasis.18Used in conjunction with phototherapy or topical steroids/vitamin D analog for plaque psoriasis at the lowest effective dose. Start at doses of 10–25 mg/day and increase dose every 2 weeks until xerosis (dry skin) to chelitis (or dry lips) appear; may take about 3 months to see a therapeutic response.18Severe psoriasis, palmoplantar pustulosis, nail psoriasis, generalized pustular psoriasis18A1After 12 weeks of therapy, the percentage reduction in the PASI score was 54%, 76%, and 54% for the groups taking acitretin 25, 35, and 50 mg/day, respectively.48 A PASI 75 response was achieved in 47%, 69%, and 53% patients in the acitretin 25, 35, and 50 mg/day groups, respectively.48
    MTXFolic acid analog that irreversibly inhibits dihydrofolate reductase in the eukaryotic cell, decreasing DNA and protein synthesis, which prevents epidermal hyperproliferation. Also decreases DNA in activated T lymphocytes by inhibiting aminoimidazole carboxyamide ribocucleotide, an enzyme involved in purine metabolism.2Single weekly dose or in 3 doses: 1 dose every 12 hours over 36 hours, or once weekly, starting at 5 to 10 mg and adjusting the dosage upward at 4-week intervals to a therapeutic dose between 15 and 25 mg/week, with a maximum dose of 25 mg/week.18,33 Low-dose folic acid (1–5 mg) is administered in 3 doses over 36 hours, starting 12–36 hours after the last MTX dose to avoid megaloblastic anemia with few reductions in efficacy.18,33,49 Or, can be given daily, except the day(s) the MTX is taken.Severe plaque psoriasis, erythrodermic, pustular, and other off-label uses50A192.7% of patients achieve a PASI 75 response after 12 weeks of high-dose MTX.51
    CyclosporineBinds to cyclophilins and forms a complex, blocking differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor. It also inhibits keratinocyte hyperproliferation.18In the absence of comorbidities (obesity and older age) it is weight-based and dosed at 3 mg/kg/day; it is usually divided into 2 doses.18 Alternative dosing is 2.5 mg/kg/day in 1 or 2 divided doses for patients with stable moderate to severe psoriasis and 4.0–6.0 mg/kg/day in 1 or 2 divided doses for patients with severe or recalcitrant psoriasis.52 The goal is the lowest effective dose possible. Taking CsA before meals may result in better absorption and bioavailability of the drug, translating into a reduced disease burden.52Severe, recalcitrant, or disabling psoriasis,53 as well as pustular, erythrodermic, and nail psoriasis52B2PASI 75 responses in up to 97% of treated patients have been reported.54
  • * Psoriasis Area and Severity Index (PASI) 75 score is reported here because it is a good tool used in clinical trials of psoriasis to determine treatment efficacy and response. A PASI 75 response indicates a 75% reduction in psoriasis lesions. Note that, because if its complexity, PASI is, in general, not calculated outside of the research setting; body surface area is another way to monitor treatment progress.

  • CsA, cyclosporine; Ig, immunoglobulin; IL, interleukin; MTX, methotrexate; PsA, psoriatic arthritis; SC, subcutaneous; TNF, tumor necrosis factor; FDA, U.S. Food and Drug Administration.