After 1 year of therapy with tofacitinib, a Janus kinase (JAK) inhibitor, patients with rheumatoid arthritis (RA) experienced stabilized bone marrow density (BMD) and positive bone turnover, according to study findings published in Osteoporosis International, resulting in significant clinical improvement and suppression of systemic inflammation.
Investigators randomly assigned 30 patients to take either 5 mg or 10 mg of tofacitinib twice daily, in combination with either methotrexate (n=23) or leflunomide (n=7), for 12 months. The participants were 27 women and 3 men with a mean age of 52.8 (range, 27-69) years in the cohort. Mean disease duration was 7.7 (range, 1-21) years. Patients with a definitive RA diagnosis, moderate-high disease activity (DAS28>3.2) at baseline, and clinical indication for targeted therapy were included.
Areal BMD was assessed with dual-energy X-ray absorptiometry (DXA) and volumetric BMD was assessed via single-slice computed tomography (QCT) at baseline and at 6 and 12 months. RA disease activity was calculated as DAS28-C-reactive protein (CRP), and functional capacity was determined by health assessment questionnaires (HAQs) that patients filled out. Investigators collected blood samples for laboratory markers of RA disease activity and biomarkers of bone turnover at baseline and at 6 and 12 months of tofacitinib treatment.
Tofacitinib treatment significantly decreased DAS28 in the 26 patients included in the final analysis after 6 months (3.31±0.91; P <.001) and 12 months (3.32±1.12; P <.001) compared with baseline (5.05±0.77). CRP decreased from 14.8±14.9 mg/L at baseline to 5.3±5.3 mg/L at 6 months (P <.001) and 7.4±7.7 mg/L at 12 months (P <.001). HAQs significantly improved from baseline (1.38±0.58) to 6 months (1.02±0.67; P =.001) and 12 months (1.02±0.71; P =.001).
Both DXA and QCT imaging showed no difference between baseline and 12-month BMD in the full cohort, supporting the ability of tofacitinib to inhibit further generalized bone loss, the researchers believe. Serum osteocalcin increased significantly after 6 months (P =.013) but not significantly after 12 months. C-terminal collagen crosslinks (CTX) significantly decreased after 6 months (P =.009) and 12 months (P =.003). Osteoprotegerin (OPG) levels increased after 6 months (P =.006) and 12 months (P =.004), and 25-hydroxy-vitamin D3 significantly increased after 6 (P =.017) and 12 months (P =.009). Parathyroid hormone (PTH), type 1 procollagen N-terminal propeptide (P1NP), RANKL, Dickkopf-1, and sclerostin did not change significantly after tofacitinib treatment.
When investigators conducted a repeated measures analysis of variance (RM-ANOVA), they found that tofacitinib treatment combined with lower anti-CCP antibody or Dickkopf-1 levels predicted DXA L2-4 vertebral BMD change, while tofacitinib treatment combined with lower age or CRP levels predicted QCT cortical BMD change.
“These results suggest that age, autoimmunity, as well as inflammatory and bone markers may influence the effects of tofacitinib treatment on 12-month BMD changes,” the study authors noted.
There were no major differences between the 5-mg and 10-mg subsets in BMD or bone biomarker changes. Therefore, study authors recommended administering the 5-mg dose to patients because the 10-mg dose may have more safety issues and is not registered for RA treatment in the European Union.
Hamar A, Szekanecz Z, Pusztai A, et al. Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis. Osteoporos Int. Published online February 9, 2021. doi: 10.1007/s00198-021-05871-0