patient care perspectives

Options After TNF Inhibitor Failure for Patients With Plaque Psoriasis

by Joel M. Gelfand, MD, MSCE


When there appears to be a loss of response to tumor necrosis factor inhibitor (TNFi) therapy, aside from ruling out adherence issues, considerations include the extent to which the disease is uncontrolled in relation to the clinician’s threshold for recommending a change in therapy.

Expert Commentary

Joel M. Gelfand, MD, MSCE

Professor of Dermatology and Epidemiology
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

“We know that being a woman, being overweight, and having lost a response to a previous biologic therapy are all factors associated with losing a response to a biologic.”

Joel M. Gelfand, MD, MSCE

One of the challenges with biologic therapies is that, although they can be very effective initially, psoriasis is a chronic lifelong disease that requires long-term disease control, and some therapies may lose their effectiveness sooner than others. For many patients, a loss of response after having had a good response initially (ie, secondary failure) is counterintuitive, as the expectation tends to be that a given medication will either work or not work for that individual. We know that being a woman, being overweight, and having lost a response to a previous biologic therapy are all factors associated with losing a response to a biologic. While there may be differences within the same class of therapies, my experience has been that patients on TNFi agents appear to lose response at a faster rate than those on agents that target the interleukin-23 (IL-23) pathway. This loss of efficacy may be related to antibody development or perhaps the underlying pathophysiology and effects of the targeted therapy (eg, treatment with TNFi therapy might activate other immune pathways, resulting in a loss of efficacy over time). 

When there appears to be a loss of response, another consideration after ruling out adherence issues is the extent to which the disease is uncontrolled in relation to the clinician’s threshold for recommending a change in therapy. This threshold depends on where the individual patient is in their journey. For instance, for a younger patient who has cycled through several biologics already, I would generally be inclined to try to keep them on their current biologic, which might involve increasing the dose or frequency of administration, or to use adjunctive therapies such as ultraviolet light or methotrexate. In contrast, for an older patient who has only ever been on a single biologic therapy and now seems to be losing their response, I would be more inclined to recommend a change because there are many other treatment options to choose from. 

In patients with secondary failure, it would not be unreasonable to try another agent in the same class. However, in the setting of primary failure (eg, the patient started adalimumab and never really had a good response), my strategy would be to switch to an agent with a different mechanism of action. As with initial therapy, the choice of therapy when switching also depends on the patient’s comorbidities. In an individual with comorbid psoriatic arthritis who fails TNFi therapy, the strongest data we have to date support the use of the IL-17 inhibitors such as secukinumab and ixekizumab, although you would not want to use IL-17 inhibitors in a patient with a history of inflammatory bowel disease. In the absence of comorbidities, either the IL-23 inhibitors or the IL-17 inhibitors are excellent choices. The anti–IL-17 agents work very quickly and the anti–IL-23 agents offer less frequent dosing. So, patient preferences can also be quite important when selecting therapy. 


Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76(2):290-298. doi:10.1016/j.jaad.2016.10.017

Kimball AB, Papp KA, Reich K, et al. Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies. Br J Dermatol. 2020;182(6):1359-1368. doi:10.1111/bjd.18484

McInnes IB, Behrens F, Mease PJ, et al; EXCEED Study Group. Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial [published correction appears in Lancet. 2020;395(10238):1694]. Lancet. 2020;395(10235):1496-1505. doi:10.1016/S0140-6736(20)30564-X

Mease PJ, Smolen JS, Behrens F, et al; SPIRIT H2H Study Group. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020;79(1):123-131. doi:10.1136/annrheumdis-2019-215386

Menter A, Armstrong A, Van Voorhees A, Liu C, Jacobson A. Brodalumab to the rescue: efficacy and safety of brodalumab in patients with psoriasis and prior exposure or inadequate response to biologics. Dermatol Ther (Heidelb). 2020;10(4):615-621. doi:10.1007/s13555-020-00411-w

Ogawa E, Sato Y, Minagawa A, Okuyama R. Pathogenesis of psoriasis and development of treatment. J Dermatol. 2018;45(3):264-272. doi:10.1111/1346-8138.14139

Sakkas LI, Zafiriou E, Bogdanos DP. Mini review: new treatments in psoriatic arthritis. Focus on the IL-23/17 axis. Front Pharmacol. 2019;10:872. doi:10.3389/fphar.2019.00872

Zhang M, Brenneman SK, Carter CT, et al. Patient-reported treatment satisfaction and choice of dosing frequency with biologic treatment for moderate to severe plaque psoriasis. Patient Prefer Adherence. 2015;9:777-784. doi:10.2147/PPA.S85773

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