The north-western part of South Africa, in particular, is well known for mineral imbalances. Aphosphorosis, resulting in rickets and osteomalacia, received a lot of attention at the turn of the nineteenth century (1882–1912). This was followed in 1997 by research on Vryburg hepatosis, another area-specific mineral imbalance–related disease in young calves reared on manganese-rich soil derived from the weathering of dolomitic (carbonate) rock formations. In 1982, a totally new syndrome (osteochondrosis) manifested in, amongst others, areas in South Africa where aphosphorosis was rife. Osteochondrosis was also identified in the south-western parts of Namibia as well as southern Botswana and other areas in South Africa. Osteochondrosis has a multifactorial aetiology and this study focused on the role of minerals, particularly phosphorus, in the development of the disease. A significant improvement in the clinical signs in experimental animals and a reduction of osteochondrosis occurred on farms where animals received bioavailable trace minerals and phosphorus as part of a balanced lick. An increase in the occurrence of the disease on farms during severe drought conditions in 2012–2013 prompted researchers to investigate the possible role of chronic metabolic acidosis in the pathogenesis of the disease.
SummaryBackgroundVedolizumab was shown to be effective and safe for patients with ulcerative colitis (UC) or Crohn's disease (CD) in the GEMINI phase 3 and long‐term safety (LTS) studies.AimTo report treatment persistence and safety results up to 2 years after enrolment in the vedolizumab extended access programme (XAP)MethodsVedolizumab XAP is a phase 3b/4, prospective, open‐label, multinational, interventional study. At rollover from GEMINI LTS, patients who were experiencing continued clinical benefit with vedolizumab received reduced dosing frequency from every 4 weeks (Q4W) to every 8 weeks (Q8W). Patient persistence on Q8W dosing, incidence of relapse, and safety 2 years after enrolment were investigated.ResultsWe enrolled 311 patients (142 UC and 169 CD). At baseline, 93.7% (UC) and 89.3% (CD) of patients were in clinical remission; 93.0% (UC) and 84.6% (CD) reduced dosing frequency to Q8W at enrolment. Of those who reduced dosing frequency to Q8W at enrolment, 93.9% (UC) and 91.6% (CD) remained on Q8W dosing; 6.1% (UC) and 8.4% (CD) re‐escalated to Q4W dosing. Relapse was reported in 9.1% (UC) and 14.0% (CD) of patients who reduced dosing to Q8W. Adverse events related to vedolizumab were infrequent; no new events were reported.ConclusionWe observed high patient persistence on vedolizumab Q8W in the first 2 years after the reduction of dosing frequency in the XAP along with low rates of Q4W dose re‐escalation and relapse. The safety profile was consistent with previous reports.ClinicalTrials.gov: NCT02743806.
LINKED CONTENTThis article is linked to Danese et al and Townsend & Subramanian papers. To view these articles, visit https://doi.org/10.1111/apt.16160 and https://doi.org/10.1111/apt.16191
Background Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis. Methods Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS. Results A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported. Conclusion High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.
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