Assessing Safety of the Transition to Generic Imatinib in Patients with Gastrointestinal Stromal Tumours

Following patent expiration of branded imatinib (Glivec®), all Dutch patients with gastrointestinal stromal tumours (GIST) switched from Glivec to generic forms. Following this switch, many patients reported new symptoms. Therefore, we conducted this observational study to assess safety of generic imatinib among patients with GIST in the Netherlands.

We included patients with GIST from four hospitals that switched from Glivec to generic imatinib. Within these patients, adverse events (AEs) without the switch to a generic were compared with AEs after the switch using a self-controlled case series design. The reference group was formed by the subset of patients who used imatinib for at least 1 year prior to the switch. As potential causes of increased AEs, we reviewed excipients and analysed plasma trough levels from 1 year prior to 1 year after the switch.

In total, 201 patients switched to three generics: Accord® (n = 107), Amarox® (n = 81), and Sandoz® (n = 13). In the reference group (n = 150), 21.3% experienced new AEs, compared with 29.9-34.6% in the different generic groups. All patients that switched to Amarox (odds ratio 2.3; 95% confidence interval (CI): 1.2-4.5) and females that switched to Accord (odds ratio 2.7; 95% CI: 1.1-7.0) experienced a significant increase in AEs. Plasma trough levels were similar among all different formulations. Apart from titanium dioxide in Amarox, no additional excipients were used in any generic form.

The transition to generic imatinib in Dutch patients with GIST was safe. After switching to generic imatinib, up to 34.6% of patients experienced new AEs, compared with 21.3% in the reference group, indicating that many AEs may have been mistakenly attributed to the switch. The small increase in AEs that we found was unlikely due to pharmacokinetics or excipients. Therefore, we argue that the nocebo effect, where negative expectations about treatment lead to worsened symptoms, played a large role.