Background The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.Objectives The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.Methods A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.ResultsThe systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.Conclusions There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.Electronic supplementary materialThe online version of this article (10.1007/s40259-017-0256-z) contains supplementary material, which is available to authorized users.

Autoimmune inflammatory rheumatic diseases (AIIRD), such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are often complicated by infection, which results in significant morbidity and mortality. The increased risk of infection is probably due to a combination of immunosuppressive effects of the AIIRD, comorbidities and the use of immunosuppressive conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and more recently, targeted synthetic DMARDs and biologic DMARDs that block specific pro-inflammatory enzymes, cytokines or cell types. The use of these various DMARDs has revolutionised the treatment of AIIRD. This has led to a marked improvement in quality of life for AIIRD patients, who often now travel for prolonged periods. Many infections are preventable with vaccination. However, as protective immune responses induced by vaccination may be impaired by immunosuppression, where possible, vaccination may need to be performed prior to initiation of immunosuppression. Vaccination status should also be reviewed when planning overseas travel. Limited data regarding vaccine efficacy in patients with AIIRD make prescriptive guidelines difficult. However, a vaccination history should be part of the initial work-up in all AIIRD patients. Those caring for AIIRD patients should regularly consider vaccination to prevent infection within the practicalities of routine clinical practice.

With the increasing availability of biosimilars, the practice of switching therapies for non-medical reasons between an originator biologic and an analogous biosimilar has become more common. The evidence to support this practice mostly comes from single-switch randomized controlled trials (RCTs) and real-world (RW) evidence studies. However, as more biosimilars of the same originator enter the market, multiple switching events between originators and biosimilars is becoming a reality, despite limited evidence to support the efficacy and safety of such practice. Some countries have established guidelines, policies, or laws related to interchangeability and/or automatic substitution, whereas others have left these practices unregulated or controlled by other components of the healthcare system. Collectively, guidelines on single non-medical switching are often vague, with even less focus given to multiple non-medical switching, leaving this practice mostly unregulated. This narrative review will first discuss the current regulatory perspectives on non-medical switching and challenges associated with switching therapies, particularly with the availability of multiple biosimilars. We will then review the current evidence from RCTs and RW studies in the light of three different multiple-switch scenarios currently taking place in clinical practice: switching between an originator and a single biosimilar, switching between biosimilars of the same originator, and the clinical practice of switching back to the originator (i.e., switchbacks) after a failure of the initial non-medical switch to the analogous biosimilar.

there was no significant increase in a bone specific analogue, deoxypyridinoline. There were significant positive correlations between pyridinoline excretion and both C reactive protein and erythrocyte sedimentation rate, whereas there was an inverse relation with grip strength. The data indicated that pyridinoline concentrations in urine are strongly associated with disease activity in patients with RA.It has been proposed that the cross links of mature collagen, pyridinoline, and its analogue, deoxypyridinoline, may provide satisfactory biochemical indices that reflect the breakdown of mature collagen, and thus be potentially useful clinical markers for the progression and activity of inflammatory disturbances of the extracellular matrix. 1 2 Pyridinoline is formed non-enzymatically, either by the reaction of two bifunctional keto-amine cross links3 or by the condensation of hydroxylysine aldehyde with an existing bifunctional keto-amine cross link.4This component is found predominantly in type I and type II collagens of bone and cartilage respectively, but not in type I collagen of skin.3 Deoxypyridinoline, however, is formed from the reaction of lysine rather than hydroxylysine as the amino group donor and appears to be located only in the type I collagen of bone and dentine.5 Both cross links are excreted in the urine2 so that measurement provides an estimate of the degradation of mature, insoluble collagen from specific tissues. Thus unlike other commonly used biochemical markers for collagen degradation, such as urinary hydroxyproline and hydroxylysine glycosides, these measurements are free from the interference resulting from the breakdown of collagen precursors or from other proteins containing collagen-like sequences, such as

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