Medication Summary
Pharmacologic therapy for psoriatic arthritis includes drugs in the following classes:
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Medication for symptomatic treatment: nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, local glucocorticoid injections
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Oral small molecules (OSM): methotrexate, sulfasalazine, cyclosporine, leflunamide, apremilast
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Tumor necrosis factor (TNF) inhibitors: etanercept, infliximab, adalimumab, golimumab, certolizumab pegol
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Interleukin (IL12/23) inhibitors: ustekinumab, guselkumab, risankizumab
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IL-17 inhibitor: secukinumab, ixekizumab
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Cytotoxic T lymphocyte–associated antigen-4 immunoglobulin fusion protein (CTLA4-Ig): abatacept
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Janus kinase (JAK) inhibitor: tofacitinib
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Class Summary
Initial treatment includes NSAIDs for joint disease and topical therapies for the skin. In many patients, this approach is sufficient to control disease manifestations, although some individuals have a worsening of psoriasis with NSAIDs. In these patients, a drug belonging to a different family of NSAIDs should be used.
For people who have morning stiffness, the optimal time for taking an NSAID may be after the evening meal and again upon awakening. Taking NSAIDs with food can reduce stomach discomfort. Any NSAID can damage the mucous layer and cause ulcers and gastrointestinal bleeding when taken for long periods. Cyclooxygenase (COX)–2 selective inhibitors are associated with a lower prevalence of gastric ulcer formation.
Indomethacin (Indocin)
Indomethacin is thought to be the most effective NSAID for the treatment of ankylosing spondylitis, although no scientific evidence supports this claim. It is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.
Ibuprofen (Motrin IB, Advil, NeoProfen)
Ibuprofen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.
Naproxen (Naprosyn, Naprelan, Aleve, Anaprox)
Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.
Diclofenac (Zorvolex, Cambia)
Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.
Oral small molecules (OSMs)
Class Summary
Oral small molecules is a term used to describe a number of immunosuppresant medication used in the treatment of various chronic diseases such as psoriasis [117]
Methotrexate (Trexall, Otrexup)
Methotrexate inhibits dihydrofolic acid reductase. It inhibits purine and thymidylic acid synthesis, which in turn interferes with DNA synthesis, repair, and cellular replication; cell cycle specific for S phase of cycle. Methotrexate may inhibit rapid proliferation of epithelial cells in skin.
Sulfasalazine (Azulfidine, Azulfidine EN)
Sulfasalazine is a 5-Aminosalicylic acid derivative that inhibits prostaglandin synthesis and reduces the inflammatory response to tissue injury. It has been shown to reduce the inflammatory symptoms of psoriatic arthritis.
Cyclosporine or ciclosporin (Neoral, Gengraf)
Cyclosporine is a calcineurin inhibitor that mainly works by suppressing T cell function.
Leflunomide (Arava)
An immunosuppressive disease-modifying antirheumatic drug DMARD. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase
Apremilast (Otezla)
Apremilast is an oral, small molecule inhibitor of phosphodiesterase-4 specific for cAMP, resulting in increased intracellular cAMP levels. The specific mechanism by which apremilast exerts it therapeutic action in psoriatic arthritis is not well defined. It is indicated for treatment of active psoriatic arthritis. It is indicated for active psoriatic arthritis.
TNF Inhibitors
Class Summary
The use of biologic response modifiers that target TNF and other cytokines represents an advance in the treatment of several diseases involving autoimmune mechanisms. Several such agents have been developed, in the form of either soluble fusion proteins (eg, etanercept) or monoclonal antibodies (eg, infliximab, adalimumab), that have shown considerable efficacy in the treatment of RA and other autoimmune diseases. [118]
Etanercept (Enbrel, Erelzi)
Etanercept is approved by the US Food and Drug Administration (FDA) for (1) treating adult patients (age ≥18 y) with chronic, moderate to severe plaque psoriasis; (2) reducing the symptoms and signs of moderate to severe polyarticular-course juvenile RA and ankylosing spondylitis; and (3) reducing the signs and symptoms and inhibiting the progression of structural damage associated with psoriatic arthritis. Therefore, etanercept may be an effective and safe alternative monotherapy for the treatment of psoriatic arthritis.
Infliximab (Inflectra, Remicade, Renflexis)
Infliximab is another TNF-neutralizing agent. It has been approved for the treatment of Crohn disease, ulcerative colitis, RA (in combination with methotrexate), ankylosing spondylitis, and psoriatic arthritis (and has shown success in reducing the signs and symptoms of this disease). [65]
However, the FDA has issued safety warnings for infliximab concerning worsening heart failure in patients with moderate to severe chronic heart failure, as well as risk for opportunistic infections such as tuberculosis, histoplasmosis, listeriosis, and pneumocystosis.
Adalimumab (Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz)
Recombinant human anti-TNF-alpha IgG1 monoclonal antibody. Blocks inflammatory activity of TNF-alpha, by specifically binding to TNF-alpha and blocks its interaction with p55 and p75 cell surface TNF receptors. It is indicated for reduction of signs and symptoms, inhibition of progression of structural damage, and improvement of physical function in adults with active psoriatic arthritis. FDA approved adalimumab-atto, adalimumab-adbm, adalimumab-adaz, adalimumab-bwwd as biosimilars and not as interchangeable drugs.
Golimumab (Simponi, Simponi Aria)
Golimumab is an FDA-approved human TNF-alpha antibody that is given every 4 weeks as a subcutaneous injection at doses of 50 mg and 100 mg. It has been shown to significantly improve symptoms of psoriatic arthritis. [6, 66]
Certolizumab pegol (Cimzia)
Other new biologic agents in clinical trials include certolizumab pegol, a PEGylated Fab' fragment of an anti–TNF-alpha monoclonal antibody. Certolizumab pegol has shown promising results in the treatment of RA and may be applicable to the treatment of psoriasis and psoriatic arthritis in the future.
Interleukin Inhibitors
Class Summary
Interleukin (IL)-12/IL-23p40, IL-23, and IL-17 receptors are associated with inflammatory and immune responses in psoriatic arthritis.
Ustekinumab (Stelara)
Ustekinumab is an anti-IL-12/23 monoclonal antibody approved for treatment of active psoriatic arthritis in adult patients. It may be administered alone or in combination with methotrexate. It is approved in doses of 45 mg or 90 mg SC given at weeks 0 and 4 and then every 12 weeks.
Guselkumab (Tremfya)
Guselkumab is a human monoclonal antibody that selectively binds to IL-23 and inhibits its interaction with the IL-23 receptor. Therefore, it inhibits the release of proinflammatory cytokines and chemokines. It is indicated for active psoriatic arthritis in adults. It may be administered alone or in combination with a conventional DMARD (eg, methotrexate).
Ixekizumab (Taltz)
Humanized monoclonal IgG4 antibody that targets interleukin-17A (IL-17A) resulting in neutralization of IL-17A’s proinflammatory effects. It is indicated for adults with active psoriatic arthritis; may be administered alone or in combination with a conventional DMARD (eg, methotrexate).
Secukinumab (Cosentyx)
Human IgG1 monoclonal antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin 17A (IL-17A). IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It is indicated for adults and children aged 2 years and older with active psoriatic arthritis.
CTLA4-Immunoglobulin
Class Summary
Abatacept is a selective costimulation modulator that inhibits T-cell activation.
Abatacept (Orencia, Orencia ClickJect)
Chimeric protein which inhibits T-lymphocyte activation by binding to CD80 and CD86 located on antigen presenting cells (APC). T-cell activation is dependent on interacting with APC. Indicated for active psoriatic arthritis in adults.
Janus Kinase (JAK) Inhibitors
Class Summary
These agents modulate the signaling pathway at the point of JAKs and preventing the phosphorylation and activation of STATs. Inhibition of JAKs also prevents cytokine- or growth factor-mediated gene expression and intracellular activity of immune cells, reduces circulating CD16/56+ natural killer cells, serum IgG, IgM, IgA, and C-reactive protein, and increases B cells.
Tofacitinib (Xeljanz, Xeljanz XR)
Tofacitinib inhibits JAK enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. In response to extracellular cytokine or growth factor signaling, JAKs activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. Inhibition of JAKs prevents cytokine- or growth factor-mediated gene expression and intracellular activity of immune cells, reduces circulating CD16/56+ natural killer cells, serum IgG, IgM, IgA, and C-reactive protein, and increases B cells. Indicated for active psoriatic arthritis (PsA) in patients who have had an inadequate response or intolerance to methotrexate or other DMARDS.
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Severe fixed flexion deformity of the interphalangeal joint.
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Comparison between sites of involvements in both hands and feet in psoriatic arthritis and rheumatoid arthritis.
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Psoriatic arthritis involving the distal phalangeal joint.
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Swelling and deformity of the metacarpophalangeal and distal interphalangeal joints in a patient with psoriatic arthritis.
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Psoriatic arthritis involving the distal phalangeal joint.
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Psoriatic arthritis involving the distal phalangeal joint.
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Asymmetrical arthritis pattern of psoriatic arthritis (fixed flexion deformity).
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Arthritis mutilans, a typically psoriatic pattern of arthritis, which is associated with a characteristic "pencil-in-cup" radiographic appearance of digits.
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Psoriatic arthritis involving the distal phalangeal joint.
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Arthritis mutilans (ie, "pencil-in-cup" deformities).
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Severe psoriatic arthritis showing involvement of the distal interphalangeal joints, distal flexion deformity, and telescoping of the left third, fourth, and fifth digits due to destruction of joint tissue.
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Psoriatic arthritis showing nail changes, distal interphalangeal joint swelling, and sausage digits.
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Left, typical appearance of psoriasis, with silvery scaling on a sharply marginated and reddened area of skin overlying the shin. Right, thimblelike pitting of the nail plate in a 56-year-old woman who had suffered from psoriasis for the previous 23 years. Nail pitting, transverse depressions, and subungual hyperkeratosis often occur in association with psoriatic disease of the distal interphalangeal joint. Courtesy of Ali Nawaz Khan, MBBS.
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Lateral radiograph of the cervical spine shows syndesmophytes at the C2-3 and C6-7 levels, with zygapophyseal joint fusion. Courtesy of Bruce M. Rothschild, MD.
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A 37-year-old man presents with a 1-year history of an erythematous and intensely pruritic rash at the bilateral soles of feet. He has mild dryness and fissuring at his hands, but no overlying scale, intense erythema, or itching like that at his feet. Diagnosis: Psoriatic arthritis (PsA), with palmoplantar pustulosis variant of psoriasis. Courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
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Patient with psoriatic arthritis involving the joints and skin displays features of arthritis mutilans with distal interphalangeal joint destruction causing a deformity and compromise to function.
Tables
Laboratory Studies |
Psoriatic Arthritis |
Rheumatoid Arthritis |
Erythrocyte sedimentation rate |
Elevated (< 100) |
Elevated (< 100) |
Rheumatoid factor |
Negative |
Positive (85% of patients) |
Antinuclear antibody |
Negative |
Positive (30% of patients) |
C-reactive protein |
Elevated |
Elevated |
Synovium |
WBC count 5000-15,000/µL, >50% polymorphonuclear leukocytes |
WBC count 2000/µL |
