Hydroxychloroquine is a frequnently used first-line therapy in patients with autoimmune diseases like RA and systemic lupus erythematosus (SLE). Based on results from 14 worldwide prospective health databases in this large study, hydroxychloroquine did not increase risk when used in RA patients without contraindications in the short term (up to 30 days) than with sulfasalazine, but an increased cardiovascular mortality risk has been observed with long term usage.

This multinational, retrospective study evaluated the safety of hydroxychloroquine, alone and used along with azithromycin, to ascertain the risk linked with its routine care usage in rheumatoid arthritis (RA).

RA patients aged 18 years or more and starting hydroxychloroquine were compared with those starting sulfasalazine with a follow-up of 30 days, with 16 severe adverse events studied. In large populations, self-regulated case series were performed for safety analysis and all users of hydroxychloroquine were considered irrespective of RA status or indication.

Severe adverse events linked with hydroxychloroquine plus azithromycin were deliberated. Records included 14 sources of claims data or electronic medical records from different countries. The adjusted hazard ratios (HRs) were estimated as per drug use.

A total of 956 374 hydroxychloroquine users, 310 350 sulfasalazine users, 323 122 hydroxychloroquine plus azithromycin users, and 351 956 hydroxychloroquine plus amoxicillin users were considered.

On comparison of 30-day hydroxychloroquine and sulfasalazine, no excess risk of severe adverse events was recognized, as confirmed  from self-regulated case series.On the other hand, long-term hydroxychloroquine usage was found to be linked with escalated cardiovascular mortality.

Azithromycin seemed to be linked increased risk of 30-day cardiovascular mortality, chest pain or angina, and heart failure (Table 1).

In RA patients, no increased risk in its short term usage of hydroxychloroquine was found. But, in the long term it may cause increased cardiovascular mortality.

With the addition of azithromycin, the risk of heart failure and cardiovascular mortality increases even with short term usage.