Research Article: Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

Date Published: October 24, 2018

Publisher: Public Library of Science

Author(s): Caterina Palleria, Luigi Iannone, Christian Leporini, Rita Citraro, Antonia Manti, Maurizio Caminiti, Pietro Gigliotti, Rosa Daniela Grembiale, Massimo L’Andolina, Giuseppe Muccari, Maria Diana Naturale, Domenico Olivo, Giuseppa Pagano Mariano, Roberta Pellegrini, Giuseppe Varcasia, Karim Abdalla, Emilio Russo, Francesco Ursini, Giovambattista De Sarro, Oreste Gualillo.


Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs’ reporting associated with biologics use in rheumatology.

We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol.

During the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

Partial Text

Inflammatory arthritides is an umbrella term comprising a heterogeneous group of chronic immune-mediated diseases affecting the joints and tendons such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and affecting ∼5% of population worldwide [1]. Patients with inflammatory arthritis experience recurring or chronic episodes of joints/tendons inflammation, leading ultimately to subversion of the normal anatomy and, consequently, a variable degree of functional disability [2].

The therapeutic approach to inflammatory arthritides has been radically changed by the development and marketing of several bDMARDs. These molecules, differently from csDMARDs, can selectively target key pathophysiological mechanisms involved in inflammatory arthritis immunopathogenesis and, despite their significantly higher cost, represent nowadays an essential bullet in the rheumatology therapeutic armamentarium. Meta-analyses of clinical trials robustly demonstrated their efficacy and the overall favorable safety profile [22]. However, when dealing with molecules potentially affecting key physiological functions such as protective immune homeostasis, safety data produced during clinical trials may be insufficient to unravel the real impact of the treatment in clinical setting. Indeed, despite the strong methodology, clinical trials have some limitations in detecting rare or uncommon adverse events, mainly related to the restrictive inclusion criteria, the narrowly-coded disease phenotype (i.e. classification criteria) and the relatively short follow-up period. Furthermore, patients in clinical trials undergo a tight follow-up protocol allowing identification and prevention of some AEs, which is often very different from the follow-up policy used in clinical practice.

Our study, although biased by some limitations including a relatively small sample size and the consequent lack of power for estimates of AEs for individual molecules, provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.




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