scholarly journals Effects of denosumab in Japanese rheumatoid arthritis patients treated with conventional anti-rheumatic drugs: 36-month extension of a phase 3 study

2021 ◽  
pp. jrheum.201376
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Satoshi Soen ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type I Collagen ◽  
Joint Destruction ◽  
Term Treatment ◽  
Drug Discontinuation ◽  
Type I ◽  
Mineral Density ◽  
Phase 3 ◽  
Long Term Treatment

Objective To evaluate safety and efficacy of long-term denosumab 60 mg every 6 (Q6M) or 3 months (Q3M) in rheumatoid arthritis (RA) patients. Methods This 12-month, randomised, double-blind, placebo-controlled, multicentre phase 3 trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese RA patients treated with placebo for 12 months then denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M); denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp (mTSS), bone erosion (ES), and joint space narrowing (JSN) scores. Results Long-term treatment better maintained mTSS and ES suppression in the P/Q3M and Q3M/Q3M versus P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS at 36 months were 2.8 (standard error 0.4), 1.7 (0.3), 3.0 (0.4), and 2.4 (0.3), respectively; corresponding changes in ES were 1.3 (0.2), 0.4 (0.2), 1.4 (0.2), and 1.1 (0.2). No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-telopeptide of type I collagen decreased rapidly at 1-month post-denosumab administration (both in the initial 12- month [Q3M, Q6M groups] and long-term treatment [P/Q3M, P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. Conclusion Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on ES progression, higher dosing frequency at an earlier treatment stage may be needed to optimise treatment. Denosumab was generally well tolerated.

ZOOM: A prospective, randomized trial of zoledronic acid (ZOL; q 4 wk vs q 12 wk) for long-term treatment in patients with bone-metastatic breast cancer (BC) after 1 yr of standard ZOL treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9005-9005 ◽  
Author(s):  
Dino Amadori ◽  
Massimo Aglietta ◽  
Barbara Alessi ◽  
Lorenzo Gianni ◽  
Toni Ibrahim ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Type I Collagen ◽  
Metastatic Breast ◽  
Term Treatment ◽  
Phase Iii ◽  
Morbidity Rate ◽  
Type I ◽  
Open Label ◽  
Long Term Treatment

9005 Background: ZOL (4 mg q 4 wk) is an established therapy for reducing the risk of debilitating skeletal-related events (SREs) in patients (pts) with bone metastases (mets) from BC. As BC treatments continue to improve pt survival, long-term SRE-reduction is increasingly important, and evaluation of modified ZOL dosing to retain efficacy with reduced adverse events (AEs) is warranted. Methods: ZOOM, a phase III prospective, randomized, open-label, multicenter study, assessed the safety and efficacy of quarterly (4 mg q 12 wk; Arm 1) vs monthly (4 mg q 4 wk; Arm 2) ZOL for ~1 yr in pts with BC who have ≥ 1 bone met, and have received ~1 yr of prior ZOL treatment (9 to 12 doses over ≤ 15 months; last dose ≤ 3 months prior). The primary endpoint was skeletal morbidity rate (SMR; number of SREs/pt/yr). Sample size to detect non-inferiority with 80% power (1-sided a = 0.025) was 420 pts. Secondary endpoints included time to first SRE, bone pain, bone marker (N-telopeptide of type I collagen; NTX) levels, and safety. Results: 425 pts were enrolled (209 in Arm 1; 216 in Arm 2); arms were well balanced for pt and disease characteristics, and anticancer therapies. SMR was similar between arms: 0.26 (95% confidence interval [CI] = 0.15, 0.37) in Arm 1 vs 0.22 (95% CI = 0.14, 0.29) in Arm 2; between-arms difference = 0.04 (upper limit of 1-tailed 97.5% CI = 0.17). Despite the proximity of 0.17 to the adjusted non-inferiority margin (0.19), the non-inferiority of Arm 1 vs 2 remains statistically significant. Safety analyses showed that ZOL was well tolerated. Renal AEs were reported in similar proportions of pts in both arms; 7 cases of osteonecrosis of the jaw were reported (1.65% overall; 4 cases in Arm 1 vs 3 in Arm 2). Conclusions: ZOOM is the first randomized trial to compare ZOL q 12 wk vs ZOL q 4 wk in BC pts after 1 yr of standard ZOL therapy. SMR was similar between arms. Limitations in study design suggest the need to confirm non-inferiority of ZOL q 12 wk in other ongoing phase III trials.

scholarly journals Effect of Stopping Risedronate after Long-Term Treatment on Bone Turnover

2011 ◽  
Vol 96 (11) ◽  
pp. 3367-3373 ◽  
Author(s):  
Richard Eastell ◽  
Rosemary A. Hannon ◽  
Dietrich Wenderoth ◽  
Jesus Rodriguez-Moreno ◽  
Andrzej Sawicki
Keyword(s):  
Postmenopausal Women ◽  
Type I Collagen ◽  
Term Treatment ◽  
Type I ◽  
Mineral Density ◽  
Open Label ◽  
Treatment Groups ◽  
Total Hip ◽  
Long Term Treatment ◽  
Hip Bmd

Abstract Context: Determining how quickly bisphosphonate treatment effects begin to regress is crucial when considering termination of treatment. Objective: Our objective was to assess the effects of 1 yr discontinuation of risedronate use in postmenopausal women with osteoporosis who had previously received risedronate for 2 or 7 yr. Design and Setting: Before initiation of the current study, placebo/5-mg-risedronate patients had received placebo for 5 yr and risedronate for 2 yr, whereas 5-mg-risedronate patients had received risedronate for a total of 7 yr. Risedronate was then discontinued for 1 yr (yr 8). Patients: Postmenopausal women with osteoporosis who had previously completed the 3-yr Vertebral Efficacy with Risedronate Therapy MultiNational (VERT-MN) pivotal trial, plus a 2-yr extension comparing risedronate or placebo for a total of 5 yr, followed by 2 yr of open-label risedronate treatment were enrolled in these trial extensions. Main Outcome Measures: Evaluations included changes in type I collagen cross-linked N-telopeptide (NTX)/creatinine (Cr) and bone mineral density (BMD) values, fracture incidence, and adverse events. Results: After 1 yr of risedronate discontinuation, NTX/Cr levels increased toward baseline in both patient groups vs. the values at the end of yr 7. In both treatment groups, off-treatment total hip and femoral trochanter BMD values decreased, whereas lumbar spine and femoral neck BMD were maintained or slightly increased. The adverse event profiles were similar between the two treatment groups during yr 8. Conclusions: One year of discontinuation of risedronate treatment in patients who had received 2 or 7 yr of risedronate therapy led to increases in NTX/Cr levels toward baseline and decreases in femoral trochanter and total hip BMD.

Serum concentrations of piroxicam in patients with rheumatoid arthritis on long-term treatment with ampiroxicam.

Ensho ◽  
1991 ◽  
Vol 11 (6) ◽  
pp. 597-605
Author(s):  
Sachiko Sugawara ◽  
Shoichiro Irimajiri ◽  
Torakichi Aoki ◽  
Shuichi Yokoyama ◽  
Sanae Ida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Term Treatment ◽  
Serum Concentrations ◽  
Long Term Treatment

Long term treatment of rheumatoid arthritis with rituximab

2009 ◽  
Vol 8 (7) ◽  
pp. 591-594 ◽  
Author(s):  
Roberto Caporali ◽  
Marta Caprioli ◽  
Francesca Bobbio-Pallavicini ◽  
Serena Bugatti ◽  
Carlomaurizio Montecucco
Keyword(s):  
Rheumatoid Arthritis ◽  
Term Treatment ◽  
Long Term Treatment
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