Antidrug antibody detection for adalimumab depends on the type of assay used: an experimental approach to help clinicians interpret diagnostic data.

OBJECTIVES: To compare different methods of antidrug antibody (ADA) against adalimumab detection in ankylosing spondylitis (AS) patients and the impact of ADA on adalimumab drug levels and mean ASDAS-CRP. METHODS: We used the acid-dissociation-radioimmunoassay (ARIA), antidrug-binding-test (ABT) and a bridging Enzyme-linked Immunosorbent Assay (ELISA) to detect ADA at 4, 12 and 24 weeks of treatment. Patients were divided into groups; all assays negative (All-neg), only ARIA positive (ARIA-only-pos), ARIA and ABT positive, bridging ELISA negative (ARIA/ABT-double-pos) and all assays positive (All-pos). RESULTS: Eighty-three consecutive AS patient were included. At week 4, 18% compared to 11% and 0% of the patients tested positive for ADA in the ARIA, ABT and bridging ELISA, respectively. At week 12 and 24, cumulative 52% and 69% patients tested positive in the ARIA, compared to 27% and 30% patients in the ABT and 2% patients in the bridging ELISA. Adalimumab levels between All-neg and ARIA-only-pos were 9.1 (5.5-12.5) and 8.5 (5.7-12.3). Drug levels differed between ARIA/ABT-double-pos (2.7 (1.3-4.4)) and All-neg (9.1 (5.5-12.5)). All-pos patients had undetectable drug levels. Mean ASDAS-CRP at week 24 differs between All-neg (1.9 (±1.2)), and All-pos (3.8 (±1.9)) and ARIA/ABT-double-pos (2.0 (±1.1)) and All-pos. CONCLUSIONS: The majority of AS patients had detectable ADA against adalimumab in the ARIA. The ARIA detects more ADA compared to the less drug tolerant ABT and bridging ELISA. The clinical relevance depends on the impact on the bio-availability of the drug. A drug level measurement therefore helps to interpret ADA data regardless of type of assay used.

Bone loss and new vertebral fractures during treatment with romosozumab: a case-report.

PURPOSE: This study aimed to illustrate the possibility of an unfavorable response to treatment with the anabolic agent romosozumab for patients with severe osteoporosis and to discuss explanations for treatment failure. METHODS: Dual-energy x-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and X-rays of the thoracolumbar spine was used to assess bone mineral density (BMD) and the presence of vertebral fractures before and after treatment with romosozumab. RESULTS: Our patient developed a decrease in the BMD of the hip, two incident new vertebral fractures, and worsening of one prevalent vertebral fracture during 1 year treatment with romosozumab. We have not detected non-adherence, there was no pretreatment with anti-resorptives, and we observed no signs of secondary osteoporosis and/or comorbidities. CONCLUSION: As the number of patients treated with romosozumab is rising, it becomes more likely that more patients will be found with new fractures and/or an unfavorable BMD response. Probably, the unfavorable response is a (bad) chance finding, but we think it is crucial for clinicians and patients to exclude nonadherence, new comorbidities and pretreatment with anti-resorptives as explanation in these patients.

Foot-related health care use in patients with rheumatoid arthritis in an outpatient secondary care center for rheumatology and rehabilitation in The Netherlands: a cohort study with a maximum of fifteen years of followup.

OBJECTIVE: To describe foot-related health care use over time in a cohort of rheumatoid arthritis (RA) patients in an outpatient secondary care center for rheumatology and rehabilitation in The Netherlands. METHODS: A total of 1,087 patients with recent-onset RA from 1995 to September 2010 were included in the study. All foot-related visits to the podiatrist, rehabilitation physician, orthopedic surgeon, and the multidisciplinary foot-care clinic were registered and described. Logistic regression techniques for longitudinal data were used to analyze the course of foot-related health care use. RESULTS: A total of 32.9% of patients visited a podiatrist in secondary care during the course of their disease. For most patients, a visit to the podiatrist took place during the first year after diagnosis. This was followed by a significant decrease in visits in the ensuing years. Nine percent of patients visited the rehabilitation physician with foot symptoms, with peak prevalences between year 10 and 11 and during year 14 of followup. The orthopedic surgeon was visited by 5.3% of patients with foot symptoms, with a significant increase in visits over time. The multidisciplinary foot-care clinic was visited by 7.5% of patients. This was significantly associated with visits to the rehabilitation physician. CONCLUSION: In an outpatient secondary care center in The Netherlands, RA patients with foot symptoms visited the podiatrist in an early stage of the disease. When foot symptoms worsened, patients visited the rehabilitation physician, who subsequently referred patients to the multidisciplinary foot-care clinic for therapeutic footwear. The orthopedic surgeon was the final step in the management of foot symptoms.