Hydroxychloroquine falls flat for RA prevention in at-risk individuals

Treatment with hydroxychloroquine (HCQ) for 12 months does not appear to prevent the development of rheumatoid arthritis (RA) among at-risk individuals, as shown in a phase II study.

The study included 144 participants (mean age 50.5 years, 79.9 percent female, 79.2 percent White, mean BMI 29.64 kg/m²) with anticyclic citrullinated peptide (anti-CCP) antibodies at least two times the upper limit of normal (ULN).

The participants were randomly assigned to receive HCQ (155 mg of active drug per 200 mg tablet) (n=71) or placebo (n=73) for 12 months, with up to 24 months of postdrug follow-up. The development of clinical RA at 36 months was the primary outcome. Secondary outcomes included safety, development of inflammatory arthritis, and participant-reported joint symptoms.

In the modified intent-to-treat population, clinical RA occurred in 21 of 69 (30.4 percent) participants in the HCQ group and 24 of 73 (32.9 percent) in the placebo group. The probability of not developing RA at 36 months did not significantly differ between the two groups (risk difference, –0.058, 95 percent confidence interval, –0.336 to 0.220; p=0.52).

Similarly, HCQ did not reduce the incidence of inflammatory arthritis, as well as the incidence and severity of joint symptoms compared with placebo.

Treatment-emergent adverse events (TEAEs) occurred in 73.2 percent of participants in the HCQ group and 75.3 percent in the placebo group. The most common TEAEs were RA (22.5 percent and 26 percent), hypertension (9.9 percent and 8.2 percent), and urinary tract infection (7 percent and 2.7 percent).

Serious TEAEs were reported in 7 percent of participants in the HCQ group and 6.8 percent in the placebo group. TEAEs led to treatment discontinuation in 25.4 percent and 23.3 percent of participants, respectively.