Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis1,2,3,4,5,6,7

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Abstract

Objective

The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA).

Methods

Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies.

Results

Some previously stated variables, including the patients׳ preference, the indication for anti-tumor necrosis factor (TNF) monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. In RA, golimumab as second-line biologic has the highest level of evidence in anti-TNF failure. The switching strategy is preferable for responder patients who experience an adverse event, whereas serious or class-specific side effects should be managed by the choice of a differently targeted drug. Secondary inadequate response to etanercept (ETN) should be treated with a biologic agent other than anti-TNF. After two or more anti-TNF failures, the swapping to a different mode of action is recommended. Among non-anti-TNF targeted biologics, to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing the first anti-TNF, the switch strategy to a second is advisable, taking in account the evidence of adalimumab efficacy in patients with uveitis. The severity of psoriasis, of articular involvement, and the predominance of enthesitis and/or dactylitis may drive the choice toward ustekinumab or secukinumab in PsA, and the latter in AS.

Conclusion

Taking in account the paucity of controlled trials, second-line biologic therapy may be reasonably optimized in patients with RA, SpA, and PsA.

Introduction

Recently, the ITABIO (Italian board for the TAilored BIOlogic therapy) task force focused on the first-line biologic choice driving variables in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) to ensure the best results in terms of clinical outcome and safety [1]. However, data from clinical trials and national registries show that first-line biologics, either combined with methotrexate (MTX) or in monotherapy, should be discontinued in approximate 30–40% of the patients due to inadequate response or adverse events in the majority of the cases [2], [3], [4]. Overall, biologic survival is lower in RA compared with PsA and AS [5], though in all the three disorders the discontinuation rate seems time-dependent with a progressive increase related to the length of follow-up [6].

To date, nine biologics including interleukin-6 (IL-6) inhibitor tocilizumab (TCZ), anti-CD20 rituximab (RTX), anti-interleukin-1 (IL-1) anakinra (ANK), anti-CD28 abatacept (ABA), and anti-tumor necrosis factor alpha agents (anti-TNFs) adalimumab (ADA), etanercept (ETN), infliximab (IFX), golimumab (GOL), certolizumab pegol (CTP), and, limited to Europe, infliximab biosimilar (bio-IFX), are approved for RA treatment, anti-TNFs, anti-interleukin-12–23 (IL-12–23) ustekinumab (UTK), and anti-interleukin-17 (IL17) secukinumab (SCK) for PsA, while only anti-TNFs and SCK are licensed for AS.

Compared to the first-line biologic therapies, the second-line ones have been less investigated in terms of effectiveness, safety, and drug survival. Moreover, controlled trials (RCTs) and current recommendations do not provide sufficient indication concerning the best strategy between switching and swapping among biologics [1]. In absence of well-defined response predictors, several variables may drive the second biologic choice in clinical practice, including the data on the efficacy, safety, disease severity, infection risk, patient׳s age and gender, route of administration, and comorbidities.

Section snippets

Objective

The aim of present paper was to provide appropriate indications for the best choice of second-line biologic therapy in patients with RA, PsA, and AS through a systematic review of the literature.

Methods

As previously described [1], a multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), including specialists in rheumatology (M.B., F.C., E.F., R.F., S.G., and L.N.), infectious diseases (D.G. and F.B.), and, immunology (M.M.), was constituted to review the literature on the existing evidence on the efficacy, safety, and the different variables influencing the second-line biologic choice in patient with RA, AS, n-rx-AxSpA, and PsA. Each ITABIO member

Literature search

The literature review was made using PubMed database to identify English-language articles related to the previously mentioned topics. Data were extracted from available recommendations, systematic reviews, and meta-analyses, RCTs, national registries of biologics, national healthcare databases, and post-marketing surveys. When these source data were not available for specific topics, the evidence was derived from open-label studies on variable sample-size clinical series.

The following drugs

General indications

As previously stated [1], some choice driving variables, including the patients׳ preference for self-administered subcutaneous route with the longest administration intervals, the indication for anti-TNF monotherapy in potential childbearing women, and its interruption at positivity of pregnancy test, are valid also for the second biologic choice after interruption of the first for inefficacy or adverse events occurrence.

Choice of the second or third biologic agent in RA

The first choice of biologic therapy for the treatment of synthetic DMARD

Conclusion

Though the lack of head-to-head trials reduces the strength of our recommendations for the proper second-line biologic choice in RA, PsA, and AS, the available data from the literature provide useful indications for the optimization of therapy in patients failing the first biologic agent, and offer the opportunity to make some final considerations. First, as previously underlined, the rather relevant percentage of at least 20% of patients with RA PsA, and AS failing the first biologic is

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  • Cited by (0)

    1

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members: Fabrizio Cantini Laura Niccoli.

    2

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members:, Ennio Giulio Favalli.

    3

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members: Maurizio Benucci.

    4

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members:, Serena Guiducci.

    5

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members: Rosario Foti.

    6

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members: Marta Mosca.

    7

    On behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO) members: Delia Goletti.

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