The use of the interleukin-6 (IL-6) receptor inhibitor, tocilizumab (TCZ), in patients with rheumatoid arthritis (RA) was associated with significant improvements in hemoglobin (Hb) and hematocrit (Hct) over 2 years of treatment, according to a study published in Seminars in Arthritis and Rheumatism.1 Other biologic disease-modifying antirheumatic drugs (DMARDs) and the small-molecule Janus kinase inhibitor, tofacitinib, were not as effective in improving anemia markers.
Comorbid in 33% to 60% of patients with RA, anemia is associated with more severe joint disease and increased risks of disability and mortality.1,2 Lead investigator Sanjoy Paul, PhD, of the University of Melbourne in Australia told Rheumatology Advisor in an email interview that basic science studies had suggested the possible beneficial roles of inflammatory cytokines, such as IL-6, on anemia markers. “However, no robust data were available at population levels to evaluate this aspect. This was the primary reason for conducting this real-world data study,” he commented.
To assess the effect of treatment with DMARDs, including tocilizumab, on anemia markers in patients with RA, the investigators analyzed data from the Centricity Electronic Medical Record (CEMR) database, which is used by more than 35,000 physicians and other providers from all US states. The database contains information on patient demographics; anthropometric, clinical and laboratory variables, including Hct and Hb; disease events; and medication data.
High Yield Data Summary
- Patients treated with TCZ demonstrated a mean and adjusted increase in Hb and Hct levels of 0.23 g/dL and 0.96%, respectively, at 24 months.
- Patients with anemia treated with TCZ demonstrated increases in Hb and Hct by 0.72 g/dL and 2.06%, respectively.
Patients who were diagnosed with RA between January 2000 and April 2016 and met the inclusion criteria were divided into groups based on medications initiated: TCZ (n=3732), tofacitinib (TOFA, n=3126), other biologic DMARD (obDMARD, n=55,964), or other non-biologic DMARD (onbDMARD, n=91,236). The percentage of patients with comorbid anemia was 26% in the TCZ group, 29% in the TOFA group, 21% in the obDMARD group, and 24% in the onbDMARD group.
Results showed that at 24 months, patients treated with TCZ demonstrated a mean and adjusted increase in Hb and Hct levels of 0.23 g/dL (95% CI, 0.14-0.42) and 0.96% (95% CI, 0.41-1.52), respectively. Patients with anemia treated with TCZ demonstrated increases in Hb and Hct by 0.72 g/dL and 2.06%, respectively. Treatment with other biologic DMARDs was not found to be associated with any significant clinically meaningful increase in Hb and Hct levels. Earlier initiation of treatment with TCZ in the disease progression pathway of RA was associated with a significantly higher likelihood of achieving a better Hb level during follow-up, while earlier therapy initiation with other biologic DMARDs or TOFA were unlikely to be associated with benefits in Hb levels.
Summary & Clinical Applicability
“Our study has shown that in patients with RA, treatment with TCZ was associated with improvement in anemia markers after adjusting for confounding factors, whereas other biologic DMARDs or TOFA were less effective in improving anemia markers,” Dr Paul told Rheumatology Advisor. “This finding would be of great interest for providers and patients. However, while this epidemiological study reports significant positive association of TCZ therapy with anemia risk factors in patients with RA, this does not establish causality. Clinical trials need to be conducted to establish the effectiveness of IL-6 targeted therapies on anemia risk factors in patients with RA.”
The investigators noted several potential limitations to the study:
- Non-availability of complete and/or reliable data on medication adherence and side-effects, disease activity and pain scores, longitudinal data on doses of individual therapies, socio-economic status, and insurance type
- Potential selection bias
Dr Paul has acted as a consultant and/or speaker for Novartis, GI Dynamics, Roche, AstraZeneca, Guangzhou Zhongyi Pharmaceutical and Amylin Pharmaceuticals LLC, and has received grants in support of investigator and investigator-initiated clinical studies from Merck, Novo Nordisk, AstraZeneca, Hospira, Amylin Pharmaceuticals, Sanofi-Avensis, Pfizer and Roche. Drs. Best, Gale, Pethoe-Schramm, and Sarsour are Roche Group employees. Dr Montvida had no disclosures.
- Paul SK, Montvida O, Best JH, Gale S, Pethoe-Schramm A, Sarsour K. Effectiveness of biologic and non-biologic antirheumatic drugs on anaemia markers in 153,788 patients with rheumatoid arthritis: new evidence from real-world data [published online August 3, 2017]. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2017.08.001
- Wilson A, Yu H-T, Goodnough LT, Nissenson AR. Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature. Am J Med. 2004;116(Suppl 7A):50S-57S.