Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study

Jennifer C.E Lane; James Weaver; Kristin Kostka; Talita Duarte-Salles; Maria Tereza F. Abrahao; Heba Alghoul; Osaid Alser; Thamir M Alshammari; Patricia Biedermann; Edward Burn; Paula Casajust; Mitch Conover; Aedin C. Culhane; Alexander Davydov; Scott L. DuVall; Dmitry Dymshyts; Sergio Fernández Bertolín; Kristina Fišter; Jill Hardin; Laura Hester; George Hripcsak; Seamus Kent; Sajan Khosla; Spyros Kolovos; Christophe G. Lambert; Johan ver der Lei; Ajit A. Londhe; Kristine E. Lynch; Rupa Makadia; Andrea V. Margulis; Michael E. Matheny; Paras Mehta; Daniel R. Morales; Henry Morgan-Stewart; Mees Mosseveld; Danielle Newby; Fredrik Nyberg; Anna Ostropolets; Rae Woong Park; Albert Prats-Uribe; Gowtham A. Rao; Christian Reich; Jenna Reps; Peter Rijnbeek; Selva Muthu Kumaran Sathappan; Martijn Schuemie; Sarah Seager; Anthony Sena; Azza Shoaibi; Matthew Spotnitz; Marc A. Suchard; Joel Swerdel; Carmen Olga Torre; David Vizcaya; Haini Wen; Marcel de Wilde; Seng Chan You; Lin Zhang; Oleg Zhuk; Patrick Ryan; Daniel Prieto-Alhambra

The comparative new user cohort studies are anchored in patients using HCQ for RA, who therefore are likely to be using HCQ at a lower dose than is currently being proposed for use in the treatment of COVID-19. We have taken into consideration that patients with RA taking HCQ may also have further auto-immune conditions such as systemic lupus erythematosus (SLE) and therefore generate the potential for confounding by indication. 50 We therefore ensured that when investigating covariate balance after propensity score stratification and matching and before unblinding study results, that we did not see unbalanced proportions of patients with a diagnosis of SLE between the groups. Negative control outcome analyses also did not identify any residual unobserved confounding in the PS analysis.