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Background: Small molecule receptor antagonists (gepants), or monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) have recently become available for migraine prophylaxis and/or acute treatment. Considering their shared mechanisms of action, if the failure to an anti-CGRP(R) mAbs preclude the effectiveness of gepants or vice versa is still unknown. Herein, we report the first case of a patient with refractory migraine responsive to the acute use of rimegepant that previously failed two different anti-CGRP(R) mAbs and with no response to other acute treatments. Finally, we performed a literature review on the use of gepants in patients that failed other anti-CGRP and/or triptans. Case: A 56-year-old female with a long history of chronic migraine without aura, fulfilling the EHF definition for a diagnosis of refractory migraine. Overall, the patient treated five not-consecutive migraine attacks. All of them were treated according to the predefined criteria. The mean (±SD) NRS before rimegepant assumption was 7.8 ± 0.9, all attacks cause at least severe impairment at onset, and no rescue medications were used. Pain free at 2 hours was achieved in three out of five attacks (60.0%), with no recurrence of migraine in the following 24 hours. The patient reported also a sustained benefit the day after the drug assumption. The response pain free was achieved after a mean time of 13.3 ± 4.5 minutes considering only attacks successfully treated (three out of five attacks). No adverse events were reported. Conclusions: In conclusion, rimegepant for acute treatment may be a viable option in patients with partial or no response to triptans that failed preventive treatments targeting the CGRP pathway, regardless to ligand or receptor. The failure of anti-CGRP(R) mAbs does not necessarily preclude the use of gepants (acute and/or preventive), but further studies are urgently needed to provide evidence on the efficacy of these treatments in managing drug-resistant migraine and to identify novel treatments for patients. [ABSTRACT FROM AUTHOR]

The reaction of the [Rh7(CO)16]3− cluster anion with Ge2+ salts, in different stoichiometric ratios and under different atmospheres, leads to the formation of new heterometallic Rh–Ge clusters, representing the first known examples of Rh carbonyl compounds containing interstitial germanium atoms. More specifically, under N2 the reaction progressively affords the new [Rh13Ge(CO)25]3− and [Rh14Ge2(CO)30]2− clusters in good yields, with the Ge atoms located in cubic and square-anti-prismatic cavities, respectively. However, under a CO atmosphere, the [Rh13Ge(CO)25]3− derivative undergoes a significant structural and chemical rearrangement giving the new compound, [Rh12Ge(CO)27]4−, where Ge is hosted in an icosahedral metal cage. All species have been characterized by IR spectroscopy and ESI mass spectrometry, and their structures have been elucidated by single-crystal X-ray diffraction. Additionally, preliminary biological tests on the [Rh13Ge(CO)25]3− and [Rh14Ge2(CO)30]2− clusters show that they are cytotoxic to various cell lines. [ABSTRACT FROM AUTHOR]

Background: The anti-calcitonin gene-related peptide (CGRP), or its receptor (CGRP/R) monoclonal antibodies (mAbs), offer targeted, effective, and tolerated drugs for migraine. However, about 25% of patients fail to achieve a clinically meaningful response, usually leading to discontinuation. These patients often have a lengthy migraine history and multiple prior preventive treatment failures, resulting in limited therapeutic options. Herein, we describe the cause for and outcome of withdrawal of anti-CGRP/R mAb and evaluate the treatment course until discontinuation. Methods: We conducted a prospective analysis on migraine patients attending the Florence Headache Center in Italy, who discontinued treatment with anti-CGRP/R mAbs. The primary objectives were to describe the reasons for anti-CGRP mAbs discontinuation and the treatment course. Secondary objectives were the evaluation of the absolute change from baseline in monthly headache days, response rates, persistence in medication overuse, absolute change from baseline of the overall number and days of analgesics use per month, change of MIDAS and HIT-6 at three, six, and 12 months, and the last month of treatment. Results: Among 472 patients, 136 (28.8%) discontinued mAb treatment after an average of 9.0 ± 6.1 (mean ± SD) months. The majority (96/136, 70.6%) discontinued due to ineffectiveness, followed by lost to follow-up during treatment (18/136, 13.1%) and adverse events (10/136, 7.3%). In total, 77.9% of the 136 patients ceased treatment within the first year. Following discontinuation, 48.5% initiated new pharmacological treatment, 39.7% were lost to follow-up, and 11.8% opted not to start another treatment. The majority of patients that started a new pharmacology treatment switched to another anti-CGRP/R (46/68, 67.6%). The second most-used treatment was onabotulinumtoxinA (7/68, 10.2%; all patients in this subgroup were naïve to this treatment), followed by an anticonvulsive medication (7/68, 10.2%). The response status (≥50% reduction in monthly headache days) was achieved by 30.5%, 34.6%, and 40.0% of patients at month 3, 6, and 12 of treatment, respectively. Considering only the comprehensive last month of treatment before withdrawn the percentage of responders was 16.9%. Conclusion: Although anti-CGRP/R mAbs have provided a substantial amelioration of migraine management, a relevant proportion of patients remains unresponsive and requires additional therapeutic support. Further research is required to identify non-responder features and address unmet needs in migraine treatment. [ABSTRACT FROM AUTHOR]