Efficacy and Safety of Systemic Treatments for Skin and Joint Manifestations in Patients With Psoriasis

March 2020 | Volume 19 | Issue 3 | Original Article | 306 | Copyright © March 2020

Published online February 3, 2020

William Abramovits , Joel Schlessinger

aDermatology Treatment and Research Center, Dallas, TX bAdvanced Skin Research Center, Omaha, NE

NCT02745080) is ongoing. The awaited complete results of these trials will provide evidence for the comparative efficacy of these IL-17A inhibitors vs TNFis and may influence treatment guidelines and recommendations.

Safety Considerations
Specific adverse effects have been observed with biologic agents and tsDMARDs. Because biologic agents and tsDMARDs are immune modulating in nature, most have warnings regarding the risks of infection and malignancy.53,54 Apremilast carries no such warning, but its use is associated with an increased risk of gastrointestinal events, unexplained weight loss, and depression; the dose requires adjustment in patients with severe renal disease.54 TNFis have been used to treat psoriasis and PsA for several years, and long-term safety in patients with PsA is well established.67,68 The risk-benefit profiles of TNFis need to be considered before treatment is initiated because all 4 available TNFis (adalimumab, certolizumab pegol, etanercept, and infliximab) were approved with warnings regarding the serious or life-threatening risks of infection and malignancy.53 These include bacterial and viral infections such as tuberculosis, listeria, legionellosis, and reactivation of latent hepatitis B and tuberculosis and invasive fungal infections such as histoplasmosis and candidiasis.54 The British Association of Dermatologists suggests that decisions regarding the use of TNFis during pregnancy be made on a case-by-case basis69; however, the use of certolizumab pegol in pregnant women results in minimal transplacental transport.70 Newer agents (ustekinumab, secukinumab, ixekizumab, and apremilast) have been approved for use in PsA, and the IL-23 inhibitor guselkumab has been approved for use in psoriasis, with no warning of potential serious or life-threatening risks.53 The safety of secukinumab has been proven through 5 years of follow-up in patients with PsA.71 For other newer agents, long-term safety has yet to be established but is being investigated. Data evaluating the use of newer biologics during pregnancy are not yet available.

Some safety signals are associated with agents according to their particular mechanism of action. TNFis have been associated with an increased risk of congestive heart failure, and monitoring of patients with mild heart failure is required to ensure that the heart failure does not worsen.53,54 Caution should be exercised when prescribing IL-17A inhibitors (secukinumab, ixekizumab, and brodalumab) to patients with inflammatory bowel disease (IBD), and these patients should be closely monitored. 53,54 Some cases of fungal Candida infection have been reported with IL-17A inhibitors.35-39,53,54 Brodalumab has a black box warning for suicidal ideation and behavior.53,54 Comparative safety data between biologic agents and tsDMARDs are lacking; ongoing head-to-head trials in PsA (EXCEED 1 and SPIRIT-H2H) are likely to allow comparisons at least in the short term. A reference arm of adalimumab was included in a recent trial of ixekizumab that also assessed safety; although the trial was not statistically powered to compare ixekizumab with adalimumab, the number of adverse events and serious adverse events appeared to be similar at week 24.38

These safety concerns must be compared with those seen with existing alternatives, particularly corticosteroids and methotrexate, the traditional mainstays of many rheumatologists. It remains to be seen whether the cost savings with these conventional therapeutics outweigh the risks with prolonged use.

Considerations for the Management or Treatment of Psoriasis With PsA
Several issues must be considered when choosing an appropriate treatment strategy to manage patients with psoriasis who have PsA as a complication. Because patients with psoriasis can have several disease domains affected, it is important to consider which manifestations are present and more pronounced in each individual. The choice of treatment should address as many facets as possible.9 The GRAPPA treatment schema for PsA summarizes recommendations according to 6 domains to aid in appropriate individualization of treatment.9 Conventional DMARDs are often used to treat PsA following an inadequate response to NSAIDs or local glucocorticoid injections.8 Most of the evidence regarding conventional DMARDs relates to psoriasis and peripheral arthritis, so these drugs may not be useful in cases with axial symptoms, enthesitis, or dactylitis. Some biologics and tsDMARDs are effective in the simultaneous treatment of multiple manifestations of psoriasis and PsA.9 Brodalumab has not demonstrated efficacy in enthesitis or dactylitis,40 whereas secukinumab and ixekizumab appeared to improve both enthesitis and dactylitis in phase III studies.51,72 Treatment choice should be discussed and agreed upon with the individual patient because certain aspects of psoriasis or PsA may have an overriding negative impact on an individual. For example, it may be more important for the patient to resolve skin manifestations in a prominent location of the body than focus on symptoms of peripheral arthritis or enthesitis. Still, the risk of PsA progression must be discussed. Optimal management may require a multidisciplinary approach.9 EULAR guidelines recommend that a dermatologist be consulted in cases with major skin involvement.8 Similarly, input from rheumatologists is likely to be beneficial in cases when PsA domains are evident. Comorbidities associated with psoriasis and PsA, such as IBD and metabolic syndrome, may further complicate the picture, and expert advice from additional specialists may be needed.8,9

Severity of disease is also important when considering the most appropriate treatment for psoriasis and PsA. GRAPPA guidelines for PsA state that the most severe element of disease will likely guide the choice of treatment.9 EULAR guidelines for PsA recommend bypassing traditional treatments and beginning therapy with a biologic agent when active disease is present with ≥ 1 adverse prognostic factor (including involvement of