Adalimumab in patients with vision-threatening uveitis: real-world clinical experience.

OBJECTIVES: Biologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group of patients treated with adalimumab. METHODS: A retrospective chart review of patients with refractory non-infectious, active uveitis treated with adalimumab was conducted. The main outcome measures were ability to reduce prednisolone dose, ability to control uveitis, final visual acuity and time to treatment failure. RESULTS: Forty-six patients with uveitis, treated with adalimumab were included in the study. The most common anatomical uveitis phenotype was panuveitis (n=17, 37.0%). The most common diagnosis was idiopathic uveitis (n=19, 41.3%). At their latest review (mean: 4.46 years; median 4.40 years), 35 (76.1%) patients were able to discontinue corticosteroids, 11 (23.9%) patients were able to taper to <7.5 mg/day and only 1 (2.2%) patient required 10 mg of prednisone. The mean visual acuity at the latest follow-up of the worse eye was logarithm of the minimum angle of resolution (logMAR) 0.42 (SD 0.72), while the mean visual acuity of the better eye was logMAR 0.19 (SD 0.34). Of the 89 eyes, 21 (23.6%) eyes improved by at least 2 lines, 5 eyes (5.6%) deteriorated by ≥2 lines while vision was unchanged in the remaining 63 (70.8%) eyes. The time to recurrence was 1 in 12.47 person-years for adalimumab, with a 17.4% (8 patient) relapse rate. There were no serious adverse events. CONCLUSIONS: This study highlights the efficacy of adalimumab in patients with vision-threatening non-infectious uveitis, preserving vision and allowing reduction of corticosteroid dose.

Effect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial.

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T12 -S1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research.

Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis.

OBJECTIVE: To assess bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in a cohort of pre- and postmenopausal women with ankylosing spondylitis (AS), and to determine any relationships with markers of bone turnover and disease activity or severity. METHODS: Fifty premenopausal and 16 postmenopausal women with AS were studied. Clinical and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and Bath AS Radiology Index (BASRI). BMD of the hip and spine was measured by DEXA, and QUS measured at the heel. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were assayed. RESULTS: Women with AS (n = 66) had reduced BMD at the hip compared to age and sex matched controls (n = 132). The mean t scores were -1.1 and -2.0, and z scores -0.4 and -0.37, for pre- and postmenopausal women, respectively. Four (6%) had osteoporosis and 34 (52%) had osteopenia according to the WHO definitions. Using a multiple regression model, femoral neck BMD was found to be significantly affected by age, body mass index, and the sacroiliac radiographic score. There were no significant correlations of BMD with disease duration or disease activity. QUS measures did not correlate with DEXA measures of BMD. Women with AS had significantly lower markers of bone formation, OC and BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels. CONCLUSION: Women with AS have reduced hip BMD, 0.39 SD below age and sex matched controls. Bone turnover in women with AS is characterized by low OC and BALP.