ObjectiveTo investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.MethodsPrevious systematic literature reviews performed by EULAR... Show moreObjectiveTo investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.MethodsPrevious systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF+ vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses.ResultsData from 28 eligible RCTs were analysed, pooling 23 studies in three subgroups: six including csDMARD-naive patients, 14 csDMARD-IR and three TNFi-IR patients. In csDMARD-naive and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88–1.18) and 1.09 (0.90–1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on three trials, the 6-month ACR20 RRR was 2.28 (1.31–3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs.ConclusionThe effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used. Show less
Mease, P.J.; Deodhar, A.A.; Heijde, D. van der; Behrens, F.; Kivitz, A.J.; Neal, J.; ... ; Banerjee, S. 2022
Objective: To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). Methods In this double... Show moreObjective: To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). Methods In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16. Results ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p=0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p <= 0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (>= 5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment. Conclusions Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA. Show less
Human cooperation is an astonishing phenomenon, as only humans exhibit such immense scale, complexity, and frequency in working together with other people. In this dissertation, I investigate how... Show moreHuman cooperation is an astonishing phenomenon, as only humans exhibit such immense scale, complexity, and frequency in working together with other people. In this dissertation, I investigate how nonverbal communication between two individuals affects cooperative success as well as methodological challenges when examining this topic in laboratory settings. To answer these questions, the dissertation comprises four chapters presenting two theoretical and two methodological studies. In the first two chapters, I demonstrate the beneficial effect of face-to-face interactions on cooperation. I subsequently show that physiological synchrony emerges during social interactions and is positively associated with cooperative success. This finding suggests that physiological synchrony might be an underlying mechanism for the beneficial effect of face contact on cooperation. In the methodological studies, I place the tasks typically used to measure cooperation into the broader context of prosocial behavior. Furthermore, I address the statistical challenges inherent to measuring synchrony between interaction partners. The cardinal point of this dissertation is that interpersonal processes that we are not aware of play a fundamental role in how we behave towards other people. Addressing methodological challenges that come along with studying dyadic interactions will greatly advance our understanding of social phenomena that make us human so unique. Show less
A central premise of the science of comparative affect is that we can best learn about the causes and consequences of affect by comparing affective phenomena across a variety of species, including... Show moreA central premise of the science of comparative affect is that we can best learn about the causes and consequences of affect by comparing affective phenomena across a variety of species, including humans. We take as a given that affect is widely shared across animals, but a key challenge is to accurately represent each species' affective experience. A common approach in the comparative study of behavior and cognition is to develop standardized experimental paradigms that can be used across species, with the assumption that if the same task is being used, we can directly compare behavioral responses. This experimental approach rests on two underlying assumptions: first, that different species' perception of and affective response to these paradigms are the same; and second, that behavioral and physiological (including endocrine and neural) responses to these paradigms are homologous; if either of these assumptions is not true, then the comparison becomes much less straightforward. Our goal in the present paper is to summarize the dominant paradigms that have been used for such comparative research, with a particular focus on paradigms common in the cooperation literature, and to critically discuss dominant assumptions about what affective states these tasks can or should measure. We then consider the advantages and drawbacks of this experimental method, and consider alternatives that may improve our understanding. We hope that this will help scholars recognize and avoid pitfalls inherent in studying affect, and stimulate them to create novel, ecologically relevant paradigms for examining affect across the animal kingdom. Show less
Cooperation forms the basis of our society and becomes increasingly essential during times of globalization. However, despite technological developments people still prefer to meet face-to-face,... Show moreCooperation forms the basis of our society and becomes increasingly essential during times of globalization. However, despite technological developments people still prefer to meet face-to-face, which has been shown to foster cooperation. However, what is still unclear is how this beneficial effect depends on what people know about their interaction partner. To examine this question, 58 dyads played an iterated Prisoner’s Dilemma game, sometimes facing each other, sometimes without face contact. Additionally, explicit feedback regarding their decisions was manipulated between dyads. The results revealed that participants were more cooperative when they saw each other compared to when they could not, and when receiving reliable compared to unreliable or no feedback. Contradicting our hypothesis that participants would rely more on nonverbal communication in the absence of explicit information, we observed that the two sources of information operated independently on cooperative behavior. Interestingly, although individuals mostly relied on explicit information if available, participants still cooperated more after their partner defected with face-to-face contact compared to no face-to-face contact. The results of our study have implications for real-life interactions, suggesting that face-to-face contact has beneficial effects on prosocial behavior even if people cannot verify whether their selfless acts are being reciprocated. Show less
Humans attend to others’ facial expressions and body language to better understand their emotions and predict goals and intentions. The eyes and its pupils reveal important social information.... Show moreHumans attend to others’ facial expressions and body language to better understand their emotions and predict goals and intentions. The eyes and its pupils reveal important social information. Because pupil size is beyond voluntary control yet reflective of a range of cognitive and affective processes, pupils in principal have the potential to convey whether others’ actions are interpreted correctly or not. Here, we measured pupil size while participants observed video-clips showing reach-to-grasp arm movements. Expressors in the video-clips were playing a board game and moved a dowel to a new position. Participants’ task was to decide whether the dowel was repositioned with the intention to be followed up by another move of the same expressor (personal intention) or whether the arm movement carried the implicit message that expressor’s turn was over (social intention). Replicating earlier findings, results showed that participants recognized expressors’ intentions on the basis of their arm kinematics. Results further showed that participants’ pupil size was larger when observing actions reflecting personal compared to social intentions. Most interestingly, before participants indicated how they interpreted the observed actions by choosing to press one of two keys (corresponding to the personal or social intention), their pupils within a split second, had already given away how they interpreted the expressor’s movement. In sum, this study underscores the importance of nonverbal behavior in helping social messages get across quickly. Revealing how actions are interpreted, pupils may provide additional feedback for effective social interactions. Show less
Behrens, F.; Tak, P.P.; Ostergaard, M.; Stoilov, R.; Wiland, P.; Huizinga, T.W.; ... ; Burkhardt, H. 2015