Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence

Drugs in R&D, Oct 2017

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with anti-tumor necrosis factor (TNF)-α agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFα failure, lack of efficacy, or adverse events. Several evidences exist on the effectiveness of switching among different TNFα inhibitors, and we reviewed the published data on the effectiveness of anti-TNFα first-, second- and third-line. Most of the studies report that the main reason for switching to a second anti-TNFα agent is represented by lack of efficacy (primary or secondary) and, more rarely, adverse events. Switchers receiving their second anti-TNFα agent have considerably poorer responses compared with non-switchers. Survival of anti-TNFα treatment appears to be superior in PsA patients when compared with rheumatoid arthritis patients. Switching from anti-TNF agents to ustekinumab or secukinumab or apremilast can represent a valid alternative therapeutic strategy.

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Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence

Drugs R D Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence Luisa Costa 0 1 2 3 4 Carlo Perricone 0 1 2 3 4 Maria Sole Chimenti 0 1 2 3 4 Antonio Del Puente 0 1 2 3 4 Paolo Caso 0 1 2 3 4 Rosario Peluso 0 1 2 3 4 Paolo Bottiglieri 0 1 2 3 4 Raffaele Scarpa 0 1 2 3 4 Francesco Caso 0 1 2 3 4 Key Points 0 1 2 3 4 0 Rheumatology, Department of Internal Medicine, Sapienza University of Rome , Rome , Italy 1 Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II , via S. Pansini 5, 80131 Naples , Italy 2 & Raffaele Scarpa 3 Geriatric Unit, Faculty of Medicine and Psychology, S. Andrea Hospital, ''Sapienza'' University of Rome , Rome , Italy 4 Rheumatology, Allergology and Clinical Immunology, Department of ''Medicina dei Sistemi'', University of Rome ''Tor Vergata'' , Rome , Italy Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with anti-tumor necrosis factor (TNF)-a agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFa failure, lack of efficacy, or adverse events. Several evidences exist on the effectiveness of switching among different TNFa inhibitors, and we reviewed the published data on the effectiveness of antiTNFa first-, second- and third-line. Most of the studies report that the main reason for switching to a second antiTNFa agent is represented by lack of efficacy (primary or secondary) and, more rarely, adverse events. Switchers receiving their second anti-TNFa agent have considerably poorer responses compared with non-switchers. Survival of anti-TNFa treatment appears to be superior in PsA patients when compared with rheumatoid arthritis patients. Switching from anti-TNF agents to ustekinumab or secukinumab or apremilast can represent a valid alternative therapeutic strategy. 1 Introduction Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis in which ocular, intestinal, metabolic and cardiovascular involvement can variably occur, suggesting a comprehensive definition of the condition as psoriatic disease [ 1–6 ]. Dactylitis, entheseal and axial involvement associated with psoriasis or its familial history, as well as rheumatoid factor (RF) negativity, represent addressing diagnostic aspects [ 7, 8 ]. Ultrasonography (US) and magnetic resonance imaging (MRI) are useful tools for describing preradiological inflammatory phases and staging synovial and periarticular involvement [ 9–12 ]. The main targets of therapy are the achievement of clinical remission, improvement of patients’ quality of life, and inhibition of structural radiological damage [ 13, 14 ]. Non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections are used prevalently in mild articular forms, and conventional synthetic diseasemodifying antirheumatic drugs (csDMARDs), including methotrexate, sulfasalazine, cyclosporine-A, and leflunomide, are required in more aggressive resistant cases [ 13, 14 ]. Biological DMARDs (bDMARDs) are recommended in severe cases, refractory to csDMARDs, possibly in the early phases of the disease. They are effective on inhibition of radiographic progression and on cutaneous and articular manifestations [ 13, 14 ]. Tumor necrosis factor (TNF)-a inhibition by use of its antagonists, represented by infliximab, etanercept, adalimumab, golimumab and certolizumab-pegol, has shown high efficacy in numerous randomized controlled trials (RCTs), and longitudinal and real-world studies [ 13–15 ]. Furthermore, despite the protective role of TNFa against microorganisms, its inhibition has been shown to be cautiously safe if associated with appropriate screening and monitoring [ 16–20 ]. According to the progressive advances on the pathogenesis of PsA, other proinflammatory cytokines, such as interleukin (IL)-17/23, and enzymatic molecules, such as phosphodiesterase 4 (PDE4), have been recognized as key factors in PsA pathogenesis. This observation has opened up additional perspectives in the management of the disease with the use of the newly developed bDMARDS ustekinumab and secukinumab of the targeted synthetic DMARD (tsDMARD) apremilast [ 13, 21 ]. This situation has generated valid therapeutic strategies in cases of primary non-response, loss of efficacy with time, intolerance, side effects and contraindication to antiTNFa agents [ 22, 23 ]. Growing evidence suggests complex and variable treatment patterns for bDMARDs in PsA patients. Discontinuation or switching of biological agents due to tolerability issues or lack of efficacy is quite common, as is loss of efficacy over time. In this review, we detail anti-TNFa failure, loss of efficacy, and withdrawal in PsA patients, and the treatment challenge that these patients subsequently face. The main published data on the effectiveness of second- and thirdline anti-TNFa (or restarting the index anti-TNFa (...truncated)


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Luisa Costa, Carlo Perricone, Maria Sole Chimenti, Antonio Del Puente, Paolo Caso, Rosario Peluso, Paolo Bottiglieri, Raffaele Scarpa, Francesco Caso. Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence, Drugs in R&D, 2017, pp. 509-522, Volume 17, Issue 4, DOI: 10.1007/s40268-017-0215-7