Dual Biologic Therapy for Recalcitrant Psoriasis and Psoriatic Arthritis

CASE REPORT

Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis

Quinn Thibodeaux, MD, Karen Ly, BA, Vidhatha Reddy, BA, Mary Patricia Smith, BS, and Wilson Liao, MD San Francisco, California

Key words: combined biologic therapy; dual biologic therapy; psoriasis; psoriatic arthritis.

INTRODUCTION Abbreviation used: Numerous biologic medications are available to treat psoriasis and psoriatic arthritis; however, many TNF: tumor necrosis factor patients experience differential responses of their skin and joints to the same agent. In patients who do not respond to biologic monotherapy or combination of a biologic with an oral systemic agent, dual but each was ineffective. She then began combina- biologic therapy is a possible treatment option. Dual tion therapy with etanercept and methotrexate, biologic therapy is rarely reported in the psoriatic which controlled her diseases for multiple years literature (Table I).1-6 We present a patient with but eventually lost efficacy for the skin. She was severe psoriatic skin and joint disease who has then put on numerous medication combinations been treated with multiple combinations of dual including etanercept plus cyclosporine, golimumab biologic therapy, including ustekinumab plus eta- plus cyclosporine, and ustekinumab plus metho- nercept for 12 months, secukinumab plus etanercept trexate. Cyclosporine and methotrexate were dis- for 6 months, and guselkumab plus etanercept for continued because of hypertension/elevated 15 months. Throughout the patient’s treatment, creatinine and intolerable gastrointestinal side ef- adverse events only occurred with the ustekinumab fects, respectively. During this trial-and-error phase, plus etanercept combination and consisted of an the patient’s joint disease improved on etanercept, increased incidence of urinary tract and upper res- whereas her skin cleared only with ustekinumab. piratory infections, including a hospitalization for After a particularly severe flare, the patient requested H2N1 flu. treatment with 2 biologics simultaneously, and after discussing the potential risks, dual biologic therapy was initiated with ustekinumab, 45 mg every CASE REPORT 3 months, and etanercept, 50 mg weekly. Adequate Our patient is a 38-year-old Asian woman with a control of her skin and joints was maintained for longstanding history of severe, generalized psoriasis more than a year, but ustekinumab was eventually since age 12 and debilitating psoriatic arthritis since discontinued because of mild but frequent urinary age 19. Her history includes numerous joint de- tract and upper respiratory infections. She was also formities of the hands and feet and both pustular and hospitalized once for H2N1 flu while on this erythrodermic psoriasis flares. Her psoriasis was regimen. Monotherapy with etanercept was again refractory to numerous topical therapies, photo- unable to control her psoriasis, so she was transi- therapy, and Goeckerman therapy. tioned to secukinumab monotherapy and noted 90% Early in her treatment course, monotherapy was improvement in her skin. Despite increasing the attempted with adalimumab followed by infliximab, maintenance dose of secukinumab from 300 mg

From the Department of Dermatology, University of California San JAAD Case Reports 2019;5:928-30. Francisco. 2352-5126 Funding sources: None. Ó 2019 by the American Academy of Dermatology, Inc. Published Conflicts of interest: Dr Wilson Liao received grant funding from by Elsevier, Inc. This is an open access article under the CC BY- the following organizations: Amgen, Janssen, Novartis, Sano- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ fi/Regeneron, and Pfizer. The remaining authors have no 4.0/). financial disclosures to disclose. https://doi.org/10.1016/j.jdcr.2019.08.015 Correspondence to: Quinn Thibodeaux, MD, UCSF Psoriasis and Skin Treatment Center, 515 Spruce Street, San Francisco, CA 94118. E-mail: [email protected].

928 V C JAAD OLUME ,N 5, ASE Table I. Reported cases of dual biologic therapy for psoriasis and psoriatic arthritis R UMBER EPORTS Patient Follow-up age/sex Diagnosis Prior therapies Combination biologic therapy Dose (mo) Adverse events 10 Cuchacovich 38/Male PsO 1 PsA Infliximab, adalimumab, Ustekinumab 1 etanercept 90 mg Q4W 1 50 mg QW [12 None et al1 etanercept, abatacept, ustekinumab Heinecke 23/Female PsO 1 PsA Ustekinumab Ustekinumab 1 etanercept 90 mg Q8W 1 25 mg BiW 8 None et al2 Ustekinumab 1 adalimumab 90 mg Q8W 1 40 mg QW Not Furuncles and reported autoimmune hemolytic anemia Babalola 62/Male PsO 1 PsA Infliximab, adalimumab, Ustekinumab 1 etanercept 90 mg Q4W 1 50 mg QW 6 Unstable angina et al3 etanercept, requiring PCI ustekinumab with DES Gniadecki 67/Male PsO 1 PsA Infliximab, etanercept, Ustekinumab 1 etanercept 90 mg Q12W 1 50 mg QW 62 Herpes zoster flares et al4 adalimumab, ustekinumab 39/Male PsO 1 PsA Etanercept, adalimumab Ustekinumab 1 etanercept 90 mg Q12W 1 25 mg QW 50 Retrotonsillar abscess 49/Female PsO 1 PsA Etanercept, efalizumab, Ustekinumab 1 adalimumab 90 mg Q12W 1 40 mg QoW 25 Erysipelas, bacterial infliximab, adalimu- pneumonia mab, ustekinumab Ustekinumab 1 golimumab 90 mg Q12W 1 100 mg Q4W 7 Skin infection of lower leg 44/Female PsO 1 PsA Etanercept, infliximab, Ustekinumab 1 adalimumab 90 mg Q12W 1 40 mg QoW 18 None adalimumab Ustekinumab 1 certolizumab 90 mg Q12W 1 200 mg QoW 36 None Torre and 33/Male Palmoplantar Mycophenolate, Ustekinumab 1 adalimumab 90 mg Q12W 1 40 mg QW 8 None Payette5 pustulosis adalimumab Rathod 46/Female PsO 1 PsA Adalimumab, Guselkumab 1 adalimumab 100 mg Q8W 1 40 mg Q2W 6 None et al6 guselkumab Current 38/Female PsO 1 PsA Adalimumab, infliximab, Ustekinumab 1 etanercept 45 mg Q12W 1 50 mg QW 12 Increased UTI/URI; study etanercept, golimu- hospitalized for mab, ustekinumab, H2N1 Flu secukinumab, Secukinumab 1 etanercept 300 mg Q2W 1 50 mg Q4W 6 None 1 1

guselkumab Guselkumab etanercept 100 mg Q4W 50 mg QW 15 None Report Case

Numerous reports exist of dual biologic therapy including a TNF-a inhibitor and either alefacept or efalizumab. Because these agents are no longer available, they have not been included in this table. BiW, Twice weekly; DES, drug-eluting stent; PCI, percutaneous coronary intervention; PsO, psoriasis; PsA, psoriatic arthritis; QoW, every other week; QW, once a week. 929 930 Case Report JAAD CASE REPORTS OCTOBER 2019 monthly to 300 mg every 2 weeks, her joint symp- The current literature on dual biologic therapy has toms began to worsen. Etanercept, 50 mg weekly, only reported combining agents that target different was eventually added to her secukinumab therapy inflammatory pathways (ie, antietumor necrosis fac- with marked improvement in joint disease activity. tor [TNF] plus antieinterleukin 12/23, see Table I). The patient continued on this dual biologic regimen For patients with comorbid psoriatic arthritis, close for 6 months with good results, but unfortunately, coordination with rheumatology may be helpful. her skin began to worsen. She was transitioned to In addition to concomitant psoriasis and psoriatic guselkumab monotherapy and noted excellent skin arthritis, dual biologic therapy has also been used clearance but continued to experience joint pain successfully for recalcitrant palmoplantar pustulosis.5 despite increasing the maintenance dose from Further study is needed to better characterize the 100 mg every 8 weeks to 100 mg every 4 weeks. efficacy and safety profile of dual biologic therapy. Etanercept, 50 mg weekly, was eventually added to Future research should also examine the potential the guselkumab to address the joint symptoms. role of bispecific monoclonal antibodies in the The patient has now been on dual biologic treatment of psoriasis and psoriatic arthritis. A therapy with 50 mg etanercept weekly and 100 mg biologic inhibiting both TNF-a and interleukin-17A guselkumab monthly for 15 months with no adverse improved psoriatic skin and joint disease during a events. Her psoriasis and psoriatic arthritis activity phase 2 trial.7 For patients with severe, debilitating have remained minimal, and she is now able to psoriatic disease who do not respond to biologic complete her activities of daily living and is no longer monotherapy and combination with oral systemic forced to comply with an intensive daily topical agents, dual biologic therapy could be considered. regimen. She continues to follow closely with the dermatology and rheumatology departments for REFERENCES coordination of her care. 1. Cuchacovich R, Garcia-Valladares I, Espinoza LR. Combination biologic treatment of refractory psoriasis and psoriatic arthritis. DISCUSSION J Rheumatol. 2012;39(1):187-193. Physicians are often reluctant to prescribe dual 2. Heinecke GM, Luber AJ, Levitt JO, Lebwohl MG. Combination use of ustekinumab with other systemic therapies: a retrospec- biologic therapy because of safety concerns. Very tive study in a tertiary referral center. J Drugs Dermatol. 2013; little data exist regarding the safety of dual biologic 12(10):1098-1102. medications for concomitant psoriasis and psoriatic 3. Babalola O, Lakdawala N, Strober BE. Combined biologic arthritis. This finding is likely because most patients therapy for the treatment of psoriasis and psoriatic arthritis: a achieve disease control with biologic monotherapy case report. JAAD Case Reports. 2015;1(1):3-4. 4. Gniadecki R, Bang B, Sand C. Combination of antitumour or through combination with an oral systemic agent. necrosis factor-alpha and anti-interleukin-12/23 antibodies in Previous reports suggest a higher rate of infectious refractory psoriasis and psoriatic arthritis: A long-term complications in patients receiving dual biologic case-series observational study. Br J Dermatol. 2016;174(5): therapy, but no large cohorts have been studied.4 1145-1146. Additionally, the possibility of a major adverse 5. Torre KM, Payette MJ. Combination biologic therapy for the treatment of severe palmoplantar pustulosis. JAAD Case Re- cardiovascular event related to combined biologic ports. 2017;3(3):240-242. 3 therapy has been reported. After careful discussion 6. Rathod D, Weinberg JM, Yamauchi PS, et al. Successful with our patient, she felt the benefit of potentially treatment of refractory plaque-type psoriasis and psoriatic improving her severe skin and joint symptoms out- arthritis with guselkumab and adalimumab combination weighed the potential safety concerns. Although she therapy: a case report. J Drugs Dermatol. 2019;18(4): 394-396. did note an increased incidence of upper respiratory 7. Mease PJ, Genovese MC, Weinblatt ME, et al. Phase ii study of and urinary tract infections while on the combination abt-122, a tumor necrosis factor- and interleukin-17a-targeted of etanercept and ustekinumab, it is difficult to assign dual variable domain immunoglobulin, in patients with psori- causation; however, she has yet to experience any atic arthritis with an inadequate response to methotrexate. adverse events on her other dual biologic regimens. Arthritis Rheumatol. 2018;70(11):1778-1789.