BackgroundIn clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of “first do no harm” may be challenged in a patient when switching from originator to biosimilar biological.AimTo describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring.MethodsInflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching.ResultsAfter inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn’s disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications.ConclusionsIn inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.Electronic supplementary materialThe online version of this article (10.1007/s00228-018-2418-4) contains supplementary material, which is available to authorized users.

In the past few years biosimilars have penetrated the market following the expiry of patents of originator variants. This offers the opportunity to apply high-tech protein products at a lower cost. In contrast to small-molecule generics, clinicians and pharmacists have found it difficult to judge the efficacy and safety profiles of complex protein products. In recent years, the European Medicines Agency (EMA) has gained knowledge on assessing comparability between biosimilars and originator products in scientific and legal areas. This article provides an overview of an extensive set of 31 previously drawn biosimilar selection criteria and describes how several of these criteria are covered by EMA regulations and guidelines. A panel of experts (authors) reviewed the criteria and produced a shortlist of 10 criteria relevant for clinicians and pharmacists.

ObjectivesIn this study the concordance between the Routine Assessment of Patient Index Data 3 (RAPID3) and the Disease Activity Score 28-joint count (DAS28) was investigated in a clinical routine outpatient setting.Patients and methodsA sample of 150 adult patients with stable RA treated with biological DMARDs (bDMARDs) was asked to complete the RAPID3 (digital or on paper) just before their outpatient routine visit during which DAS28 assessment took place. The RAPID3 correlation with and the agreement in four DAS28 categories was studied using Spearman’s rank order and Cohen’s observed kappa statistics respectively. The positive (PPV) and negative (NPV) predictive values were calculated to test whether RAPID3 could make distinction in active disease (DAS28 >3.2) or not.ResultsA moderate correlation (ρ 0.576) and a poor kappa value of 0.13 were found in the whole study population. Patients reported a higher disease severity than was measured by DAS28. The PPV of RAPID3 for active disease by DAS28 was 0.59 (95 % CI 0.50–0.68) and the NPV was 0.91 (95 % CI 0.75–0.98) with a sensitivity and specificity of 96 and 40 % respectively.DiscussionWhile RAPID3 correlates to some extent with DAS28 at the group level, agreement between RAPID3 and DAS28 at the individual patient level is to poor to rely on RAPID3 results in monitoring patients with RA. RAPID3 tends to over-report disease activity as assessed by DAS28.

This manuscript describes the System of Objectifi ed Judgement Analysis (SOJA) method applied to gonadotropin-releasing hormone (GnRH) agonists and antagonists in prostate cancer. The following selection criteria were used: effi cacy, safety, tolerability, dosage frequency, user-friendly formulation, drug interactions, precaution and documentation. The GnRH agonists goserelin and leuprorelin show the highest scores, mainly based on more extensive documentation compared with the agonists buserelin and triptorelin. The antagonists abarelix and degarelix show low scores, based on a higher incidence of adverse events, a higher dosage frequency, more drug interactions and a more limited documentation compared with the agonists. The availability of a generic formulation of leuprorelin may lead to a reduction in cost.

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