AB0903 Dual Immunomodulatory Therapies in Psoriatic Disease

Abstract

BackgroundSince the advent of numerous biologic therapies and small molecular drugs targeting specific cytokines and signalling pathways; the management of patients with psoriatic arthritis (PsA) has significantly improved. However, at least 40% of PsA patients exhibit an incomplete or failure to respond to these treatments.While the outcomes of patients with psoriasis (Pso) has dramatically improved with monoclonal antibody therapies targeting IL-23 and IL-17A; achieving a measurable low disease activity state such as minimal disease activity (MDA) for musculoskeletal manifestations of psoriatic disease is infrequent. Given the complex and heterogeneity of signalling pathways, cytokines and cell types resulting in synovio-entheseal disease in PsA; new treatment strategies must be evaluated to induce deep and sustainable clinical responses in all the phenotypic domains of psoriatic disease (cutaneous, synovium, entheseal and axial). (1)In patients who do not achieve remission in all clinical domains on a biologic monotherapy or combination of a biologic therapy with an oral synthetic agent; dual targeted anti-cytokines strategies or combined biologic with a targeted oral small molecule are a possible treatment option.ObjectivesTo describe a series of four patients with recalcitrant psoriatic disease and failure to respond to previous treatment regimens who were successfully treated with dual immunomodulatory therapies.MethodsPatients on dual immunomodulatory therapies attending our department were prospectively followed and clinical response monitored.Results:Table 1.Age/genderDiagnosisprior therapiescombination therapydoseadverse eventsCase 149/ MalePsA + PsOMethotrexate, adalimumab, etanercept, infliximab, golimumab, certolizumab, ustekinumab, secukinumab, ixekizumabBaracitinib + infliximab4mg OD + 5mg/kg Q8WNoneCase 251/ MalePsA + PsOMethotrexate, etanercept, adalimumab, ustekinumab, infliximab, secukinumab, apremilast, ixekizumab, brodalumab, guselkumabAdalimumab + guselkumab40mg QoW +100mg Q8WNoneCase 351/ FemalePsA + PsOMethotrexate, sulphasalazine, etarnercept, certolizumab, leflunomide, infliximab, adalimumab, secukinumab, ustekinumab, tofacitinib, abatacept, baracitinibAdalimumab + tofacinitib40mg QoW + 5mg BDNoneCase 439/ MalePsA +PsOMethotrexate, etanercept, ustekinumab, adalimumab, secukinumab, ixekizumab, sulphasalazineIxekizumab + baracitinib80mg Q4W+ 4mg ODNoneFigure 1.Mini-Arthroscopy of left knee for Case 3 prior to starting dual immunomodulator therapy.(A) Macroscopic aspects of synovitis (B) Synovium vascularizationConclusionMultiple pathways and mediators are responsible for the initiation of and sustained joint inflammation and damage seen in PsA. A phase II trial of ABT-122, a biologic engineered to target both TNF and IL-17A showed statistically significant superior efficacy outcomes at multiple time points based on ACR50, ACR70 and psoriasis outcome measures (PASI75/PASI90) when compared to adalimumab, with similar safety profile.(2)Safety concerns such as infectious risks are important considerations with such strategies; however, the targeted second-generation anti-cytokine biologics and targeted JAK-I have exhibited improved safety profiles.(3) In our small case series, patients have not, to date, experienced adverse events of combination therapy.