Factors associated with treatment intensification in patients with axial spondyloarthritis and high disease activity in clinical practice.

OBJECTIVE: To investigate which factors are associated with treatment intensification (TI) in axial spondylarthritis (axSpA) patients with high disease activity (HDA). METHODS: Patients with axSpA and HDA (Ankylosing Spondylitis Disease Activity Score [ASDAS]≥2.1) from the Dutch SpA-Net registry were included. TI was defined as: 1) higher dose or shorter interval of the same drug, 2) switch from current drug to another due to inefficacy, or 3) addition of a new drug. Only anti-inflammatory drugs were considered. Primary determinants considered were ASDAS, Assessment of SpondyloArthritis international Society Health Index (ASAS HI) and physician global (PhGA). Acceptable symptom state according to patient (PASS-patient) or physician (PASS-physician) were included in sensitivity analyses. Patient-centered and physician-centered logistic regression models were used to investigate the association between potential determinants and TI. RESULTS: In total, 121 patients with HDA were included. TI was conducted in a minority (41/121, 33.9%), and mainly involved a switch or addition of a drug. In multivariable regression analyses, a higher ASDAS was associated with TI in the patient-centered model (ORASDAS = 1.94, [95%CI 1.00-3.74]). However, in the physician-centered model, this association attenuated, and PhGA or PASS-physician were the primary factors associated with TI (ORPhGA = 1.71 [1.24-2.34]; ORPASS-physician = 94.95). Interestingly, patient-centered factors (ASAS HI/PASS-patient/education level) did not contribute to TI. CONCLUSION: In practice, treatment is intensified in a minority of axSpA patients with HDA. Physician-centered factors are associated with the decision to change treatment, independently of disease activity or patient perspective. Further research is needed to better understand these decisions.

Go or no-go for treat-to-target in axial spondyloarthritis?

PURPOSE OF REVIEW: For almost a decade, treat-to-target (T2T) has been advocated as a management strategy for axial spondyloarthritis (axSpA), despite a lack of trial evidence. Recently, the first and only published T2T trial in axSpA did not meet its primary endpoint. The purpose of this review is to discuss whether we should continue with a T2T approach in axSpA and to describe some experiences with T2T in clinical practice. RECENT FINDINGS: The trial showed no superiority of T2T compared with usual care; however, several secondary trial outcomes and the health economic analysis actually favoured T2T, and there are conceivable reasons for the negative trial results. Furthermore, several knowledge gaps related to an optimal T2T approach in axSpA were identified. In clinical practice, a T2T approach was applied to only a limited extent, possibly because of several challenges. SUMMARY: Despite one negative trial, it is too early to abandon T2T in axSpA. Not only more evidence from clinical trials but also research on the optimal target and management of all facets of axSpA, are highly needed. For successful implementation of T2T in clinical practice, it is important that barriers and facilitators to application are identified and subsequently addressed.

Performance of 3 Composite Measures for Disease Activity in Peripheral Spondyloarthritis.

OBJECTIVE: To investigate concurrent validity and discrimination of the Disease Activity Index for Psoriatic Arthritis (DAPSA) score, Psoriatic Arthritis Disease Activity Score (PASDAS), and Ankylosing Spondylitis Disease Activity Score (ASDAS) in peripheral spondyloarthritis (pSpA) in clinical practice. METHODS: Data from a Dutch registry for SpA (SpA-Net) were used. Predefined hypotheses on concurrent validity of the composite measures with 15 other outcome measures of disease activity, physical function, and health-related quality of life were tested. Concurrent validity was considered acceptable if ≥ 75% of the hypotheses were confirmed. Discrimination was assessed by stratifying patients in DAPSA, PASDAS, and ASDAS predefined disease activity states and studying mean differences in health outcomes by 1-way ANOVA. Further, the concordance in disease activity states was determined. All analyses were repeated in subgroups with and without psoriasis (PsO). RESULTS: DAPSA, PASDAS, and ASDAS scores were available for 191, 139, and 279 patients with pSpA, respectively. The concurrent validity and discrimination of all composite measures were acceptable, as the strength of correlations were as hypothesized in ≥ 75% of the studied correlations. With increasing disease activity states, scores in nearly all outcome measures worsened significantly. The DAPSA, PASDAS, and ASDAS classified 22%, 56%, and 48% of the patients, respectively, in the 2 highest disease activity states. Stratified analyses for concomitant PsO revealed no relevant subgroup differences. CONCLUSION: The performance of DAPSA, PASDAS, and ASDAS in pSpA was acceptable, and independent of concomitant PsO. Due to discrepancy in classification, the validity of existing thresholds for disease activity states warrants further study in pSpA.

Posttraining transcranial magnetic stimulation of striate cortex disrupts consolidation early in visual skill learning.

Practice-induced improvements in skilled performance reflect "offline " consolidation processes extending beyond daily training sessions. According to visual learning theories, an early, fast learning phase driven by high-level areas is followed by a late, asymptotic learning phase driven by low-level, retinotopic areas when higher resolution is required. Thus, low-level areas would not contribute to learning and offline consolidation until late learning. Recent studies have challenged this notion, demonstrating modified responses to trained stimuli in primary visual cortex (V1) and offline activity after very limited training. However, the behavioral relevance of modified V1 activity for offline consolidation of visual skill memory in V1 after early training sessions remains unclear. Here, we used neuronavigated transcranial magnetic stimulation (TMS) directed to a trained retinotopic V1 location to test for behaviorally relevant consolidation in human low-level visual cortex. Applying TMS to the trained V1 location within 45 min of the first or second training session strongly interfered with learning, as measured by impaired performance the next day. The interference was conditional on task context and occurred only when training in the location targeted by TMS was followed by training in a second location before TMS. In this condition, high-level areas may become coupled to the second location and uncoupled from the previously trained low-level representation, thereby rendering consolidation vulnerable to interference. Our data show that, during the earliest phases of skill learning in the lowest-level visual areas, a behaviorally relevant form of consolidation exists of which the robustness is controlled by high-level, contextual factors.

Time-limited consolidation and task interference: no direct link.

Perceptual skills improve with daily practice (Fahle and Poggio, 2002; Fine and Jacobs, 2002). Practice induces plasticity in task-relevant brain regions during an "offline" consolidation period thought to last several hours, during which initially fragile memory traces become stable (Karni, 1996; Dudai, 2004). Impaired retention of a task if followed by training in another task is considered evidence for the instability of memory traces during consolidation (Dudai, 2004). However, it remains unknown when after training memory traces become stable and resistant against interference, where in the brain the neuronal mechanisms responsible for interference are localized, and how these mechanisms produce interference. Here, we show in human participants strong interference between two visual skill-learning tasks for surprisingly long time intervals between training periods (up to 24 h). Interference occurred during asymptotic learning, but only when stimuli were similar between tasks. This supports a strong contribution to interference of low-level visual cortical areas (Karni and Bertini, 1997; Ahissar and Hochstein, 2004), where similar stimuli recruit overlapping neuronal populations. Our finding of stimulus-dependent and time-independent interference reveals a fundamental limit in cortical plasticity that constrains the simultaneous representation of multiple skills in a single neuronal population, rather than a time-limited consolidation process.

A detailed analysis of rats' spatial memory in a probe trial of a Morris task.

In the present study, we evaluated the search behavior of rats during a probe trial of a Morris water escape task. More specifically, the spatial memory during different stages of a 2 min probe trial in different zones was examined. After rats were trained for 4 days with four trials per day, their spatial memory was tested in a first probe trial. The rats showed a preference for the target quadrant during each of four 30-s intervals. The time in the annulus decreased across the four 30-s intervals. The preference for the previous target quadrant was also observed in a second probe trial, when the rats had received additional training for 4 days with four trials per day. However, the time spent in the annulus was highest during the first 30-s of the probe trial, and was lower and similar during the next three 30-s intervals. Therefore, probe trials of 60s seem to underestimate the spatial ability of rats. It appears that using a quadrant for assessing the performance may overestimate the spatial ability of a rat. Our findings suggest that the evaluation of the spatial memory of rats in a probe trial in the Morris water escape task requires a more detailed analysis.