Recent Publications by CFE Educators

OBJECTIVE

To assess the long-term safety profile of bimekizumab (BKZ) in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).

METHODS

Safety data pooled from six integrated phase IIb/III studies in axSpA and PsA are reported (to the July 2022 data-cut for phase III) for patients who received ≥1 dose of BKZ 160 mg every 4 weeks. Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rate per 100 patient-years (EAIR/100 PY).

RESULTS

The axSpA and PsA safety pools included 848 (total BKZ exposure: 2034.4 PY) and 1407 patients (2590.8 PY), respectively. TEAEs occurred at an EAIR/100 PY of 136.9 in axSpA and 139.6 in PsA; study discontinuation due to TEAEs was low (axSpA: 2.7/100 PY; PsA: 3.1/100 PY). The three most frequently reported TEAEs were SARS-CoV-2 (COVID-19) infection (axSpA: 7.8/100 PY; PsA: 8.8/100 PY), nasopharyngitis (axSpA: 8.2/100 PY; PsA: 7.7/100 PY) and upper respiratory tract infection (axSpA: 5.0/100 PY; PsA: 5.6/100 PY). EAIR/100 PY of oral candidiasis was 3.7 in axSpA and 4.2 in PsA; most events were mild/moderate. EAIR of BKZ discontinuation due to oral candidiasis was low (both axSpA and PsA: 0.3/100 PY). No systemic fungal infections or cases of active tuberculosis were reported. EAIRs of adjudicated definite/probable inflammatory bowel disease, uveitis, adjudicated major adverse cardiovascular events and adjudicated suicidal ideation/behaviour were low.

CONCLUSION

Overall, BKZ demonstrated good tolerability, with TEAE EAIRs comparable between axSpA and PsA cohorts, remaining stable over extended treatment periods. No new safety signals were identified.

TRIAL REGISTRATION NUMBERS

NCT02963506 (BE AGILE); NCT03355573 (BE AGILE 2); NCT03928704 (BE MOBILE 1); NCT03928743 (BE MOBILE 2); NCT04436640 (BE MOVING); NCT02969525 (BE ACTIVE); NCT03347110 (BE ACTIVE 2); NCT03895203 (BE OPTIMAL); NCT03896581 (BE COMPLETE); NCT04009499 (BE VITAL).

BACKGROUND

Increased body mass index (BMI) in midlife is a recognized risk factor for renal cell carcinoma (RCC), but data on lifetime BMI patterns and their associations with RCC and subtypes remain limited.

METHODS

In the National Institutes of Health-American Association of Retired Persons Diet and Health Study (n = 204,364), the authors evaluated lifetime body weight patterns using: 1) BMI at ages 18, 35, 50, and baseline (mean [SD]: 61.6 [5.3] years); 2) BMI trajectory across adulthood; 3) cumulative exposure to excess weight, measured as weighted years overweight/obese (WYO); and 4) BMI change between specific ages. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall RCC (n = 1425), aggressive RCC (n = 583), fatal RCC (n = 339), and histologic subtypes, including clear cell RCC (ccRCC, n = 541), papillary RCC (pRCC, n = 146), and chromophobe RCC (chRCC, n = 64).

RESULTS

Higher BMI at all ages was associated with greater hazard of overall RCC and all subtypes (HR, 1.10-1.40 per 5-unit increase), except chRCC (HR, 0.80-0.98). Similar patterns were observed for BMI trajectories indicating weight gain during adulthood to overweight/obesity, compared to maintaining normal BMI. Higher WYO (per SD increase) was associated with an elevated hazard of overall RCC (HR, 1.17; 95% CI, 1.12-2.22), aggressive RCC (HR, 1.21; 95% CI, 1.13-1.29), fatal RCC (HR, 1.16; 95% CI, 1.06-1.27), and ccRCC (HR, 1.20; 95% CI, 1.13-1.30), but not pRCC (HR, 1.13; 95% CI, 0.97-1.32) and chRCC (HR, 0.92; 95% CI, 0.68-1.25). BMI reduction of ≥10%, particularly after age 50 (HR, 0.72; 95% CI, 0.52-0.99), was associated with lower RCC hazard.

CONCLUSIONS

Lifetime excess weight and adult weight gain were associated with increased risk of RCC, particularly ccRCC, whereas weight loss was associated with reduced risk.

OBJECTIVE

To investigate the clinical response at week 52 in patients with AS who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16.

METHODS

ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease [AS Disease Activity Score (ASDAS) 1.3] at both week 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS 1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs) through week 52.

RESULTS

Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS 1.3. The incidence of TEAEs was similar in both groups through week 52. No new safety signals were observed.

CONCLUSION

Patients with AS who did not achieve ASDAS 1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation.

TRIAL REGISTRATION

ClinicalTrials.gov, http://clinicaltrials.gov, NCT03350815.