Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis

Abstract

Numerous biologic medications are available to treat psoriasis and psoriatic arthritis; however, many 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 biologic therapy is a possible treatment option. Dual biologic therapy is rarely reported in the psoriatic literature (Table I).1Cuchacovich R. Garcia-Valladares I. Espinoza L.R. Combination biologic treatment of refractory psoriasis and psoriatic arthritis.J Rheumatol. 2012; 39: 187-193Google Scholar, 2Heinecke G.M. Luber A.J. Levitt J.O. Lebwohl M.G. Combination use of ustekinumab with other systemic therapies: a retrospective study in a tertiary referral center.J Drugs Dermatol. 2013; 12: 1098-1102PubMed Google Scholar, 3Babalola O. Lakdawala N. Strober B.E. Combined biologic therapy for the treatment of psoriasis and psoriatic arthritis: a case report.JAAD Case Reports. 2015; 1: 3-4Abstract Full Text Full Text PDF Scopus (12) Google Scholar, 4Gniadecki R. Bang B. Sand C. Combination of antitumour necrosis factor-alpha and anti-interleukin-12/23 antibodies in refractory psoriasis and psoriatic arthritis: A long-term case-series observational study.Br J Dermatol. 2016; 174: 1145-1146Google Scholar, 5Torre K.M. Payette M.J. Combination biologic therapy for the treatment of severe palmoplantar pustulosis.JAAD Case Reports. 2017; 3: 240-242Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 6Rathod D. Weinberg J.M. Yamauchi P.S. et al.Successful treatment of refractory plaque-type psoriasis and psoriatic arthritis with guselkumab and adalimumab combination therapy: a case report.J Drugs Dermatol. 2019; 18: 394-396Google Scholar We present a patient with severe psoriatic skin and joint disease who has been treated with multiple combinations of dual biologic therapy, including ustekinumab plus etanercept for 12 months, secukinumab plus etanercept for 6 months, and guselkumab plus etanercept for 15 months. Throughout the patient's treatment, adverse events only occurred with the ustekinumab plus etanercept combination and consisted of an increased incidence of urinary tract and upper respiratory infections, including a hospitalization for H2N1 flu.Table IReported cases of dual biologic therapy for psoriasis and psoriatic arthritisPatient age/sexDiagnosisPrior therapiesCombination biologic therapyDoseFollow-up (mo)Adverse eventsCuchacovich et al1Cuchacovich R. Garcia-Valladares I. Espinoza L.R. Combination biologic treatment of refractory psoriasis and psoriatic arthritis.J Rheumatol. 2012; 39: 187-193Google Scholar38/MalePsO + PsAInfliximab, adalimumab, etanercept, abatacept, ustekinumabUstekinumab + etanercept90 mg Q4W + 50 mg QW>12NoneHeinecke et al2Heinecke G.M. Luber A.J. Levitt J.O. Lebwohl M.G. Combination use of ustekinumab with other systemic therapies: a retrospective study in a tertiary referral center.J Drugs Dermatol. 2013; 12: 1098-1102PubMed Google Scholar23/FemalePsO + PsAUstekinumabUstekinumab + etanercept90 mg Q8W + 25 mg BiW8NoneUstekinumab + adalimumab90 mg Q8W + 40 mg QWNot reportedFuruncles and autoimmune hemolytic anemiaBabalola et al3Babalola O. Lakdawala N. Strober B.E. Combined biologic therapy for the treatment of psoriasis and psoriatic arthritis: a case report.JAAD Case Reports. 2015; 1: 3-4Abstract Full Text Full Text PDF Scopus (12) Google Scholar62/MalePsO + PsAInfliximab, adalimumab, etanercept, ustekinumabUstekinumab + etanercept90 mg Q4W + 50 mg QW6Unstable angina requiring PCI with DESGniadecki et al4Gniadecki R. Bang B. Sand C. Combination of antitumour necrosis factor-alpha and anti-interleukin-12/23 antibodies in refractory psoriasis and psoriatic arthritis: A long-term case-series observational study.Br J Dermatol. 2016; 174: 1145-1146Google Scholar67/MalePsO + PsAInfliximab, etanercept, adalimumab, ustekinumabUstekinumab + etanercept90 mg Q12W + 50 mg QW62Herpes zoster flares39/MalePsO + PsAEtanercept, adalimumabUstekinumab + etanercept90 mg Q12W + 25 mg QW50Retrotonsillar abscess49/FemalePsO + PsAEtanercept, efalizumab, infliximab, adalimumab, ustekinumabUstekinumab + adalimumab90 mg Q12W + 40 mg QoW25Erysipelas, bacterial pneumoniaUstekinumab + golimumab90 mg Q12W + 100 mg Q4W7Skin infection of lower leg44/FemalePsO + PsAEtanercept, infliximab, adalimumabUstekinumab + adalimumab90 mg Q12W + 40 mg QoW18NoneUstekinumab + certolizumab90 mg Q12W + 200 mg QoW36NoneTorre and Payette5Torre K.M. Payette M.J. Combination biologic therapy for the treatment of severe palmoplantar pustulosis.JAAD Case Reports. 2017; 3: 240-242Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar33/MalePalmoplantar pustulosisMycophenolate, adalimumabUstekinumab + adalimumab90 mg Q12W + 40 mg QW8NoneRathod et al6Rathod D. Weinberg J.M. Yamauchi P.S. et al.Successful treatment of refractory plaque-type psoriasis and psoriatic arthritis with guselkumab and adalimumab combination therapy: a case report.J Drugs Dermatol. 2019; 18: 394-396Google Scholar46/FemalePsO + PsAAdalimumab, guselkumabGuselkumab + adalimumab100 mg Q8W + 40 mg Q2W6NoneCurrent study38/FemalePsO + PsAAdalimumab, infliximab, etanercept, golimumab, ustekinumab, secukinumab, guselkumabUstekinumab + etanercept45 mg Q12W + 50 mg QW12Increased UTI/URI; hospitalized for H2N1 FluSecukinumab + etanercept300 mg Q2W + 50 mg Q4W6NoneGuselkumab + etanercept100 mg Q4W + 50 mg QW15NoneNumerous reports exist of dual biologic therapy including a TNF-α 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. Open table in a new tab Numerous reports exist of dual biologic therapy including a TNF-α 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. Our patient is a 38-year-old Asian woman with a longstanding history of severe, generalized psoriasis since age 12 and debilitating psoriatic arthritis since age 19. Her history includes numerous joint deformities of the hands and feet and both pustular and erythrodermic psoriasis flares. Her psoriasis was refractory to numerous topical therapies, phototherapy, and Goeckerman therapy. Early in her treatment course, monotherapy was attempted with adalimumab followed by infliximab, but each was ineffective. She then began combination therapy with etanercept and methotrexate, which controlled her diseases for multiple years but eventually lost efficacy for the skin. She was then put on numerous medication combinations including etanercept plus cyclosporine, golimumab plus cyclosporine, and ustekinumab plus methotrexate. Cyclosporine and methotrexate were discontinued because of hypertension/elevated creatinine and intolerable gastrointestinal side effects, respectively. During this trial-and-error phase, the patient's joint disease improved on etanercept, whereas her skin cleared only with ustekinumab. After a particularly severe flare, the patient requested treatment with 2 biologics simultaneously, and after discussing the potential risks, dual biologic therapy was initiated with ustekinumab, 45 mg every 3 months, and etanercept, 50 mg weekly. Adequate control of her skin and joints was maintained for more than a year, but ustekinumab was eventually discontinued because of mild but frequent urinary tract and upper respiratory infections. She was also hospitalized once for H2N1 flu while on this regimen. Monotherapy with etanercept was again unable to control her psoriasis, so she was transitioned to secukinumab monotherapy and noted 90% improvement in her skin. Despite increasing the maintenance dose of secukinumab from 300 mg monthly to 300 mg every 2 weeks, her joint symptoms began to worsen. Etanercept, 50 mg weekly, was eventually added to her secukinumab therapy with marked improvement in joint disease activity. The patient continued on this dual biologic regimen for 6 months with good results, but unfortunately, her skin began to worsen. She was transitioned to guselkumab monotherapy and noted excellent skin clearance but continued to experience joint pain despite increasing the maintenance dose from 100 mg every 8 weeks to 100 mg every 4 weeks. Etanercept, 50 mg weekly, was eventually added to the guselkumab to address the joint symptoms. The patient has now been on dual biologic therapy with 50 mg etanercept weekly and 100 mg guselkumab monthly for 15 months with no adverse events. Her psoriasis and psoriatic arthritis activity have remained minimal, and she is now able to complete her activities of daily living and is no longer forced to comply with an intensive daily topical regimen. She continues to follow closely with the dermatology and rheumatology departments for coordination of her care. Physicians are often reluctant to prescribe dual biologic therapy because of safety concerns. Very little data exist regarding the safety of dual biologic medications for concomitant psoriasis and psoriatic arthritis. This finding is likely because most patients achieve disease control with biologic monotherapy or through combination with an oral systemic agent. Previous reports suggest a higher rate of infectious complications in patients receiving dual biologic therapy, but no large cohorts have been studied.4Gniadecki R. Bang B. Sand C. Combination of antitumour necrosis factor-alpha and anti-interleukin-12/23 antibodies in refractory psoriasis and psoriatic arthritis: A long-term case-series observational study.Br J Dermatol. 2016; 174: 1145-1146Google Scholar Additionally, the possibility of a major adverse cardiovascular event related to combined biologic therapy has been reported.3Babalola O. Lakdawala N. Strober B.E. Combined biologic therapy for the treatment of psoriasis and psoriatic arthritis: a case report.JAAD Case Reports. 2015; 1: 3-4Abstract Full Text Full Text PDF Scopus (12) Google Scholar After careful discussion with our patient, she felt the benefit of potentially improving her severe skin and joint symptoms outweighed the potential safety concerns. Although she did note an increased incidence of upper respiratory and urinary tract infections while on the combination of etanercept and ustekinumab, it is difficult to assign causation; however, she has yet to experience any adverse events on her other dual biologic regimens. The current literature on dual biologic therapy has only reported combining agents that target different inflammatory pathways (ie, anti–tumor necrosis factor [TNF] plus anti–interleukin 12/23, see Table I). For patients with comorbid psoriatic arthritis, close coordination with rheumatology may be helpful. In addition to concomitant psoriasis and psoriatic arthritis, dual biologic therapy has also been used successfully for recalcitrant palmoplantar pustulosis.5Torre K.M. Payette M.J. Combination biologic therapy for the treatment of severe palmoplantar pustulosis.JAAD Case Reports. 2017; 3: 240-242Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Further study is needed to better characterize the efficacy and safety profile of dual biologic therapy. Future research should also examine the potential role of bispecific monoclonal antibodies in the treatment of psoriasis and psoriatic arthritis. A biologic inhibiting both TNF-α and interleukin-17A improved psoriatic skin and joint disease during a phase 2 trial.7Mease P.J. Genovese M.C. Weinblatt M.E. et al.Phase ii study of abt-122, a tumor necrosis factor- and interleukin-17a-targeted dual variable domain immunoglobulin, in patients with psoriatic arthritis with an inadequate response to methotrexate.Arthritis Rheumatol. 2018; 70: 1778-1789Google Scholar For patients with severe, debilitating psoriatic disease who do not respond to biologic monotherapy and combination with oral systemic agents, dual biologic therapy could be considered.