Background and Aims There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40–59 years/≥60 years]. Methods IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. Results A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40–59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40–59 1.21; p = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62–0.98, p = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. Conclusions Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections.
Background Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe. The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5–10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing, and dose of MTX in PMR remain unclear, and therefore, our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients. Methods We set up a double-blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15 mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse, prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52. Discussion No relapsing PMR patients were chosen, since the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exists. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects. Trial registration Dutch Trial Registration, NL8366. Registered on 10 February 2020
BackgroundAfter adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment.ObjectiveTo validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders.MethodsA diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity.Results137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab.ConclusionsIn contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.
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