Monoclonal antibodies against CGRP (R): non-responders and switchers: real world data from an austrian case series.

OBJECTIVE: Assessement of the responder and non-responder rate to consecutive monoclonal CGRP-antibody (CGRP-mAb) treatment, the presence of side effects, analysis of predictors of response and loss-of-effectiveness evaluation over time. METHODS: We conducted a retrospective analysis including 171 patients with episodic (EM) or chronic migraine (CM), who received one, two or three different CGRP-mAbs. Non-response was defined as ≤ 50% reduction of monthly migraine days (MMDs) in EM and ≤ 30% reduction of MMDs in CM after 3 months of treatment. RESULTS: 123 (71.9%) responded to the first mAb. Side effects led to treatment discontinuation in 9 (5.3%) patients. Of the 26 patients who did not respond to the first mAb or experienced a loss of efficacy over time, 11 (42.3%) responded to the second and two (28.6%) of 7 to the third monoclonal antibody. Poor response to therapy was associated with a higher monthly migraine frequency (p = 0.028), a higher number of prior preventive migraine therapies (p = 0.011) and medication overuse (p = 0.022). CONCLUSION: Our findings support mAb-class switch in non-responders or in patients experiencing a loss of effectiveness. The use of a third CGRP-mAb could be beneficial for some patients.

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response.

OBJECTIVE: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. SUBJECTS AND METHODS: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. RESULTS: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. CONCLUSION: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.

Identifying distinct latent classes of pitch-shift response consistency: Evidence from manipulating the predictability of shift direction.

Auditory feedback plays an important role in regulating our vocal pitch. When pitch shifts suddenly appear in auditory feedback, the majority of the responses are opposing, correcting for the mismatch between perceived pitch and actual pitch. However, research has indicated that following responses to auditory perturbation could be common. This study attempts to explore the ways individual speakers would respond to pitch perturbation (using an opposing response or a following response) from trial to trial. Thirty-six native speakers of Mandarin produced the vowel /a/ while receiving perturbed pitch at a random time (500 ~ 700 ms) after vocal onset for a duration of 200 ms. Three blocks of 30 trials that differed in the pitch-shift stimulus direction were recorded in a randomized order: (a) the down-only condition where pitch was shifted downwards 250 cents; (b) the up-only condition where pitch was shifted upwards 250 cents; and (c) the random condition where downshifts and upshifts occurred randomly and were equally likely. The participants were instructed to ignore the pitch shifts. Results from the latent class analysis show that at the individual level across trials, 57% of participants were switchers, 28% were opposers, and 15% were followers. Our results support that speakers produce a mix of opposing and following responses when they respond to perturbed pitch. Specifically, the proportion of followers was conditional on the expectancy of pitch-shift stimulus direction: More followers were observed when the pitch-shift stimulus direction was predictable. Closer inspection of the levels of response consistency in different time phases shows that a particular mechanism (opposing or following) was initially implemented; the two mechanisms may alternate in the middle phase; and then finally, the pitch-shift response was featured as a particular mechanism near the end phase.

Reasons for Brazilian women to switch from different contraceptives to long-acting reversible contraceptives.

OBJECTIVES: Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort. STUDY DESIGN: Women of 18-50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013. RESULTS: Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was "fear of becoming pregnant" while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~95.0/100 women/year for the three methods. CONCLUSIONS: Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.