Effectiveness of Implementation Interventions in Musculoskeletal Healthcare: A Systematic Review

BackgroundImplementing new knowledge into clinical practice is a challenge, but nonetheless crucial to improve our healthcare system related to the management of musculoskeletal pain. This systematic review aimed to assess the effectiveness of implementation interventions within musculoskeletal healthcare. MethodsWe searched Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus. Any type of randomised controlled trials investigating implementation strategies or interventions in relation to musculoskeletal pain conditions were included. Risk of bias were assessed using the Cochrane Risk of Bias 2 tool. Data analysis was done using frameworks from Powell et al. 2015, and Waltz et al. 2015 and outcomes were identified by Thompson et al. 2022 or self-made outcome domains were established. ResultsThe literature search yielded 14,265 original studies, of which 38 studies from 31 trials, with 13,203 participating healthcare professionals and 30,320 participating patients were included in the final synthesis. Nineteen studies had a high risk of bias, sixteen had a moderate risk of bias, and three had a low risk of bias. Twenty distinct implementation interventions were identified. A significant heterogeneity in the utilised outcome measurements was observed, thereby rendering a meta-analysis infeasible; consequently, all outcomes were classified into six outcome domains for healthcare professionals, seven for patients and one for cost-effectiveness. ConclusionsOur findings suggest that some implementation interventions may have a tendency towards a statistically significant positive effect in favour of the intervention group on the outcome domain "Adherence to the implemented interventions" for healthcare professionals in the included studies. The remaining outcome domains yielded varying results; therefore, these findings should be interpreted with caution. Future high-quality trials with clear reporting and rationale of implementation strategies and interventions utilising standardised nomenclature are needed to further advance our understanding of this area. Trial registrationOpen Science Framework, DOI: 10.17605/OSF.IO/SRMP

Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab : A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA)

Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians' choice of treatment. COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p -values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment

Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA)

Abstract Introduction Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians’ choice of treatment. Methods COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. Results Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p-values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. Conclusions Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment. Trial Registration ClinicalTrials.gov identifier NCT04533737