ABSTRACT
Background: Low-dose glucocorticoid (GC) therapy is widely used in RA but the true balance of beneft and harm is still unknown. Objectives: We studied the effects of prednisolone (5 mg/day, 2 years) in RA patients aged 65+, requiring adjustment of antirheumatic therapy (DAS28≥2.60). Methods: Pragmatic double-blind placebo-controlled randomized trial;all co-treatments and changes therein were allowed during the trial except longterm open label GC;Ca/D supplementation was advised in all patients. Minimal exclusion criteria were tailored to seniors. Harm outcome: the number of patients with ≥1 serious adverse event (SAE), or ≥1 'other adverse event of special interest' (other AESI). Other AESI comprised any AE (except worsening of RA) causing study discontinuation, and GC-specifc events (Table 1). Beneft outcomes: improvement in disease activity (DAS28) and joint damage progression (Sharp/van der Heijde). Longitudinal mixed models analyzed the data. Given prior knowledge we report one-sided 95% confdence limit (95%CL) and statistical tests, performed only for the main outcomes. Results: We randomized 451 RA patients in 7 EU countries, 449 received the intervention;of these 63% prednisolone vs 61% placebo patients completed 2 years of follow up. Discontinuations were similar in both groups: for AE (14%) and active disease (4%);the remainder mostly for 'trial fatigue' and covid-related access issues (20%). Mean time on study drug was 19 (SD 8) months. 70% of patients were female, mean age was 72 (max 88) years, RA duration 11 years;67% were RF+, 56% ACPA+, 96% had joint damage on radiographs: mean score 20, median 8. Mean DAS28 was 4.5. Most patients (79%) were on current DMARD treatment, including 14% on biologics;47% had previously used GC, 14% changed DMARD therapy at baseline. Patients had mean 2.1 active comorbidities, and used median 7 drugs. Beneft: Disease activity rapidly declined to stabilize after 1 year (Figure 1), and was lower on prednisolone (adjusted mean difference in DAS28 over 2 years: 0.37, 95%CL 0.23, p<0.0001). The contrast in early (3-month) response was larger in 331 patients adherent to protocol on stable treatment: mean difference in DAS28 0.62 (95%CL 0.44), more responders on prednisolone (Figure 1). Sig-nifcant time-treatment interaction in secondary analyses suggested a decrease in contrast after the frst year, most likely caused by signifcantly more changes in DMARD treatment on placebo. Joint damage progression over 2 years was signifcantly lower on prednisolone: mean 0.6 (SD 1.9) v 1.8 (6.4) score points on placebo, difference 1.2 (95%CL 0.2, p=0.02). Harm: 60% prednisolone vs 49% placebo patients experienced the harm outcome: adjusted RR 1.24, 95%CL 1.04, p=0.02;number needed to harm 9.5 (Table 1). During the study 1 vs 2 patients died, and 3 vs 0 died within 5 months of discontinuation. Per 100 patient-years, AE totaled 278 in prednisolone vs 206 in placebo patients, and the difference was most marked for infections (Table 1);these were mostly mild or moderately severe. Other GC-specifc AESI were rare without relevant differences. Conclusion: Add-on low dose prednisolone has benefcial long-term effects on disease activity and damage progression in senior RA patients on standard treatment. The tradeoff is a 24% increase in patients with mostly mild to moderate AE, suggesting a favorable balance of beneft and harm.
ABSTRACT
The answer to the question whether COVID-19 is a hype or not depends on how we define a hype. The article loosely builds on philosophical discussions about hypes in knowledge work and information sciences. The central idea is to make clear that hypes always imply a certain overload of information and that the paradoxical outcome of this that it is not just information that is piling up but also disinformation. It is argued that it is in this sense (and only in this sense) that COVID-19 is a hype. How we respond to this hype depends very strongly on subjective sensitivities towards both information and desinformation.