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)