Clinical Edge Journal Scan

Commentary: Ongoing therapy options in RA, June 2023

Dr. Jayatilleke scans the journals, so you don't have to!

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Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

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