No abstract

Treatment of PHPT patients with cinacalcet for up to 5.5 yr maintained normocalcemia, reduced plasma PTH, increased serum phosphate and alkaline phosphatase with no significant effects on aBMD, and was well tolerated.

ObjectiveThe efficacy and safety of subcutaneous tocilizumab (TCZ-SC) versus subcutaneous placebo (PBO-SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs in the BREVACTA study.MethodsPatients (n = 656) were randomized 2:1 to receive TCZ-SC 162 mg every other week or PBO-SC every other week for 24 weeks; 20% previously received anti–tumor necrosis factor treatment. Escape therapy with TCZ-SC 162 mg weekly was offered from week 12 for inadequate response. The primary end point was the American College of Rheumatology 20% improvement (ACR20) response at week 24. The key secondary outcomes were radiographic progression and safety.ResultsTCZ-SC was superior to PBO-SC for ACR20 response at week 24 (60.9% versus 31.5%; P < 0.0001). All secondary end points showed TCZ-SC to be superior to PBO-SC, including ACR50 and ACR70 response (40% and 20% for TCZ-SC, respectively, and 12% and 5% for PBO-SC, respectively; P < 0.0001 for both) and Disease Activity Score in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean change in modified Sharp/van der Heijde score was significantly lower in the TCZ-SC group than the PBO-SC group (0.62 versus 1.23; P = 0.0149). Adverse events (AEs) and serious AEs (SAEs) were comparable between the TCZ-SC and PBO-SC groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection was the most common SAE in 2.1% and 1.8% of patients, respectively. More injection site reactions occurred with TCZ-SC than PBO-SC (7.1% versus 4.1%). No anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths in the TCZ-SC group and 0 in the PBO-SC group.ConclusionTCZ-SC every other week had significantly greater efficacy, including ACR end points and inhibition of joint damage, compared with PBO-SC. TCZ-SC was well tolerated and its safety profile was comparable with that of previous intravenous TCZ studies.

Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.