Calcitonin Gene-related Peptide Receptor Antagonist Research Articles

Antinociceptive effect of the calcitonin gene-related peptide receptor antagonist BIBN4096BS in mice with bacterial cystitis.

Patients with urinary tract infections (UTIs) suffer from urinary frequency, urgency, dysuria, and suprapubic pain, but the mechanisms by which bladder afferents sense the presence of uropathogens and encode this information is not well understood. Calcitonin gene-related peptide (CGRP) is a 37-mer neuropeptide found in a subset of bladder afferents that terminate primarily in the lamina propria. Here, we report that the CGRP receptor antagonist BIBN4096BS lessens lower urinary tract symptoms and prevents the development of pelvic allodynia in mice inoculated with uropathogenic Escherichia coli (UPEC) without altering urine bacterial loads or the host immune response to the infection. These findings indicate that CGRP facilitates the processing of noxious/inflammatory stimuli during UPEC infection. Using fluorescent in situ hybridization, we identified a population of suburothelial fibroblasts in the lamina propria, a region where afferent fibers containing CGRP terminate, that expresses the canonical CGRP receptor components Calcrl and Ramp1. We propose that these fibroblasts, in conjunction with CGRP+ afferents, form a circuit that senses substances released during the infection and transmit this noxious information to the central nervous system.NEW & NOTEWORTHY Afferent C fibers release neuropeptides including calcitonin gene-related peptide (CGRP). Here, we show that the specific CGRP receptor antagonist, BIBN409BS, ameliorates lower urinary tract symptoms and pelvic allodynia in mice inoculated with uropathogenic E. coli. Using fluorescent in situ hybridization, we identified a population of suburothelial fibroblasts in the lamina propria that expresses the canonical CGRP receptor. Our findings indicate that CGRP contributes to the transmission of nociceptive information arising from the bladder.

Long-Term Management of Migraine With OnabotulinumtoxinA (Botox) vs Calcitonin Gene-Related Peptide Antibodies (Anti-CGRP).

In this literature review, we will evaluate the effectiveness of OnabotulinumtoxinA (Botox) and anti-calcitonin gene-related peptide (anti-CGRP) in the treatment of migraine headaches. Both therapies are frequently prescribed for managing and preventing migraines and have received Food and Drug Administration (FDA) approval. The mechanism of action, side effects, compliance, cost-effectiveness, and migraine treatment provided by these two medicines were compared in the analysis of several studies. Many studies found that as Botox was administered by a doctor every three months and had fewer side effects than anti-CGRP, which is self-administered every month, it was more compliant than anti-CGRP. After examining the data, Botox is believed to be the most effective therapy. Although both therapies are efficient, this article compares them to determine which is the best management strategy.

A retrospective analysis of migraine prophylaxis with anti-CGRP monoclonal antibodies at the hospital of Lithuanian University of Health Sciences Kaunas Clinics

Background. Migraine is a primary headache disorder described by episodic attacks that can progress to chronic migraine. Preventive treatment of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) is currently being widely investigated worldwide.Materials and methods. A total of 85 patients with migraine were enrolled in a retrospective study conducted in 2019-2021. Demographic and clinical data were collected and analyzed. Subjects were divided into groups by migraine course: chronic migraine (CM) and episodic migraine (EM), and according to the medicine used (erenumab, fremanezumab). Treatment efficacy was assessed at 3 and 6 months after the start of treatment. A reduction of >50% in monthly headache days (MHDs) was considered a good response. Statistical analysis was performed using IBM SPSS statistics 27.0, the χ² test of homogeneity, Fisher’s exact, Student’s t, and Mann-Whitney tests.Results. Of the 85 migraine patients, 75 (88.2%) were women. EM was diagnosed in 33 (38.8%) and CM in 52 (61.2%) patients. After treatment, the number of MHDs was significantly reduced in both anti-CGRP mAbs therapy groups (p<0.001). The response to anti-CGRP mAbs was similar between the EM and CM groups. A slightly better response was achieved with fremanezumab than erenumab (83.3% vs. 73.1% at 3 months; 83.3% vs. 65.7% at 6 months), but the difference was not significant (p=0.541; p=0.149). In 24 (58.5%) patients initially given 70 mg erenumab, after a median follow-up of 3 months (interquartile range: 2-6) it was decided to increase the dose of erenumab to 140 mg due to insufficient effect. The initial dose was increased more often in patients with chronic migraine (p=0.027).Conclusions. Erenumab and fremanezumab are equally effective and equivalent for both migraine types. It was observed that more than half of the patients required a dose increase when treated with erenumab 70 mg, especially in CM group.

Comparative Efficacy and Safety of Five Anti-Calcitonin Gene-Related Peptide Agents for Migraine Prevention: A Network Meta-Analysis.

Anti-Calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies (mAbs) for migraine prevention. In this network meta-analysis (NMA), the efficacy and safety of migraine treatments including different doses of atogepant and CGRP mAbs were evaluated to provide a reference for future clinical trials. A search using PubMed, Embase and Cochrane Library identified all randomized controlled trials (RCTs) published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias. In this study, 24 articles were considered for analysis. Regarding effectiveness, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225mg in change from baseline of migraine days (SMD=-0.49,95%CI[-0.62, -0.37]) and 50% response rate (RR=2.98,95%CI[2.16,4.10]), while the optimal choice for reducing acute medication days was monthly erenumab 140mg(SMD=-0.68,95%CI[-0.79, -0.58]). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240mg and quarterly fremanezumab 675mg. There was no significant difference in discontinuation due to AEs between interventions and placebo. All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225mg, monthly erenumab 140mg, and daily atogepant 60mg were effective interventions with fewer side effects.

S2543 Pan-Colitis Secondary to Calcitonin Gene-Related Peptide (CGRP) Antagonist for Migraines

S2543 Pan-Colitis Secondary to Calcitonin Gene-Related Peptide (CGRP) Antagonist for Migraines

Preventive and abortive treatment of migraine with traditional drugs. The state of the art

IntroductionMigraine is a chronic neurological disease, with a prevalence of 15.2% in Brazil. It is 2.2 times more prevalent in women, predominantly in the 18-50 age group. Its pathophysiological mechanism is still not completely understood. Possibly headache attacks and symptoms are associated with cortical spreading depression, the trigeminovascular system, neurogenic inflammation, vasodilation and genetic vulnerability.ObjectiveThis is a narrative review of preventive and abortive treatment of migraine.CommentMigraine treatment is based on three pillars: patient education, treatment of the disease itself or prevention of attacks, and acute treatment of headache attacks. The therapeutic classes of traditional drugs used in migraine prevention are beta-blockers, tricyclic antidepressants, calcium channel antagonists or blockers, and anticonvulsant neuromodulators. Specific drugs used in the treatment of headache attacks are triptans or serotonergic 5-HT1B/1D receptor agonists, ditans or 5-HT1F receptor agonists, and gepants or CGRP receptor antagonists.ConclusionTraditional drugs used in the preventive or abortive treatment of migraine are considered to be effective. Through modulation of the disease mechanisms, there is a reduction in the frequency, intensity and duration of headache attacks, and also in the disability caused by the headache. All this to improve the quality of life of patients. The therapeutic classes of traditional drugs used in migraine prevention are beta-blockers, tricyclic antidepressants, antagonists or blockers of calcium channels and anticonvulsant neuromodulators. Specific drugs used in the treatment of headache attacks are triptans or serotonergic 5-HT1B/1D receptor agonists,ditans or 5-HT1F receptor agonists, and gepants or CGRP receptor antagonists.

Novel peptide calcitonin gene-related peptide antagonists for migraine therapy.

It has previously been shown that the peptide (34Pro,35Phe)CGRP27-37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides. Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies. A 10 amino acid-containing peptide VPTDVGPFAF-NH2 (P006) was identified as a key candidate to take forward for in vivo evaluation, where it was shown to be an effective antagonist after intraperitoneal injection into mice. P006 was formulated as a preparation suitable for nasal administration by spray drying with chitosan to form mucoadhesive microcarriers (9.55 ± 0.91 mm diameter) and a loading of 0.2 mg peptide per 20 mg dose. The project has demonstrated the potential of these novel small peptide CGRP antagonists, to undergo future preclinical evaluation as anti-migraine therapeutics.

Conventional and unconventional treatments for migraine

Migraine is one of the leading causes of disability in humans. It causes significant deterioration in patients' lives and prevents daily functioning. Its main symptoms include photophobia, an enormous stabbing headache, nausea and vomiting. In addition, it can be accompanied by tinnitus, visual disturbances or dizziness. Before diagnosing migraine, serious intracranial pathology or other neurological conditions should be ruled out. Treatment of acute migraine is difficult due to significant rates of nonresponse to medications and the difficulty in predicting individual response to a particular agent or dose. A new class of drugs, calcitonin gene-related peptide (CGRP) antagonists, has been approved for the prevention of migraine in adults. In contrast, effective first-line therapies for mild to moderate migraine are over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) and combination analgesics containing paracetamol, aspirin and caffeine.

Efficacy and Safety of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Preventing Migraines: A Systematic Review.

The neuropeptide calcitonin gene-related peptide (CGRP) is an essential pathophysiological treatment for migraines. A unique class of medications called CGRP monoclonal antibodies target CGRP and its receptor and have demonstrated promising benefits in the treatment and prevention of migraines. This study sought to identify and assess the quality of existing systematic reviews about the effectiveness of CGRP antibodies for preventing migraines, as well as systematically review and synthesize the evidence on these topics. This included the four Food and Drug Administration (FDA)-approved medications erenumab, galcanezumab, fremanezumab, and eptinezumab. The effectiveness and safety of these monoclonal antibodies in preventing migraines should also be examined in light of patient characteristics, and any gaps in the body of knowledge should be noted in order to suggest new lines of investigation. Data gathering included a thorough search of internet databases (PubMed, Cochrane Library, Web of Science, and Scopus) for relevant research released between 2018 and 2023. The findings imply that CGRP monoclonal antibodies are efficient and secure for preventing migraines and may be considered a first-line alternative for treating migraines and drug misuse. The results further imply that combination treatment with CGRP antibodies and onabotulinumtoxinA may enhance the prevention of migraine in adults. With suggestions for more studies to find and address these variables, the significance of genetic and epigenetic factors in the progression of pediatric patients' acute postoperative pain to chronic postsurgical pain is underlined. All four anti-CGRP monoclonal antibodies, erenumab, fremanezumab, galcanezumab, and eptinezumab, were shown to be safe and effective for the prevention of migraine when the research additionally looked at their individual effectiveness and safety. Additionally, the study discovered considerable variances in effectiveness amongst various groups. However, further investigation is required to establish the best time and dosage and the effect of patient characteristics on the effectiveness and safety of these medications.

Translated article] Consensus recommendations on the preventive treatment of migraine

ObjectiveThe objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. MethodologyRecommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. ResultsAfter both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). ConclusionsThe high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis

Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis.

Switching between anti-calcitonin gene-related peptide monoclonal antibodies: A comparison of monthly and quarterly dosing

BackgroundAnti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have dramatically changed preventive treatment options for patients with migraine. Although there is emerging real-world evidence on the use of CGRPmAbs globally, the change in efficacy and safety after switching between CGRPmAbs owing to patients' frequency of hospital visits preference remains unknown. MethodsWe conducted a single-centre, retrospective, real-world study of patients with migraine who first received galcanezumab for 3 or 4 months and then switched to fremanezumab at Keio University Hospital. We investigated changes in monthly migraine days (MMD), responder rate, and adverse effects such as injection site reactions. ResultsMMD increased only by 0.7 (95% CI, −4.1–5.5; p = 0.748) after 4 months of treatment with fremanezumab (6.1, 95% CI, 2.3–9.9) compared to before switching (5.4, 95% CI, 2.2–8.6). Furthermore, switching from galcanezumab to fremanezumab produced only minor adverse events, such as injection site reactions. ConclusionsAfter switching from galcanezumab to fremanezumab out of the desire to visit the hospital less often, the reduction in MMD compared to baseline was sustained, and no serious adverse effects were observed.

Calcitonin Gene-Related Peptide Systemic Effects: Embracing the Complexity of Its Biological Roles-A Narrative Review.

The calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed throughout the human body. While primarily recognized as a nociceptive mediator, CGRP antagonists are currently utilized for migraine treatment. However, its role extends far beyond this, acting as a regulator of numerous biological processes. Indeed, CGRP plays a crucial role in vasodilation, inflammation, intestinal motility, and apoptosis. In this review, we explore the non-nociceptive effects of CGRP in various body systems, revealing actions that can be contradictory at times. In the cardiovascular system, it functions as a potent vasodilator, yet its antagonists do not induce arterial hypertension, suggesting concurrent modulation by other molecules. As an immunomodulator, CGRP exhibits intriguing complexity, displaying both anti-inflammatory and pro-inflammatory effects. Furthermore, CGRP appears to be involved in obesity development while paradoxically reducing appetite. A thorough investigation of CGRP's biological effects is crucial for anticipating potential side effects associated with its antagonists' use and for developing novel therapies in other medical fields. In summary, CGRP represents a neuropeptide with a complex systemic impact, extending well beyond nociception, thus offering new perspectives in medical research and therapeutics.

Combined Prophylaxis of Chronic Migraine with OnabotulinumtoxinA and Anti-CGRP Antibodies

Objective: To evaluate the efficacy of adding large molecule anti-calcitonin gene-related peptide monoclonal antibodies (mAbs) to onabotulinumtoxinA (OBT-A) for chronic migraine prevention. Background: Chronic migraine (CM) is a highly prevalent, debilitating disorder that leads to personal, social, and economic burdens. Both OBT-A and mAbs are proven safe and effective in chronic migraine prevention. The use of combination therapy has not been formally studied but may prove more effective than either monotherapy alone in select patients. Methods: This is a retrospective chart review of patients with chronic migraine, treated with OBT-A, who received additional mAb preventative therapy. The primary endpoint was migraine headache days per month (MHD) after 3 months of combined therapy. Secondary endpoints included total headache days per month, headache intensity, disability level, and use of abortive medications. Results: Of 1503 patients reviewed, 133 met inclusion criteria. At 3 months of combined therapy, mean reduction of MHD from baseline was 6.2 (95% CI 4.91 to 7.49, p < 0.0001). Nearly 2/3rd of patients (60.9%) experienced ≥ 50% MHD reduction. Fewer patients reported high disability level (14.6% [17/126], compared to 29.4%) and high headache intensity (13.0% [16/119], compared to 51.3%) at 3 months (all p < 0.0001). A reduction in abortive medication doses needed and discontinuation of concomitant oral preventative medications was also noted in 15.8% and 6.8% of patients, respectively. Conclusions: Combined therapy with OBT-A and mAbs is well-tolerated, effective in further reducing migraine frequency, and may improve quality of life for patients with CM refractory to monotherapy.

Update of Gepants in the Treatment of Chronic Migraine.

Despite the unmet therapeutic needs of patients with chronic migraine (CM) and/or medication overuse, available treatment options are limited. Recently, four calcitonin gene-related peptide receptor antagonists, known as gepants, have been approved for the treatment of migraine. This review focuses on the preventive treatment of CM with gepants and highlights recent findings. Two randomized controlled trials (RCTs) have shown promising results for rimegepant and atogepant as preventive treatments for CM. In an RCT targeting patients with CM, atogepant demonstrated a significant reduction in the mean monthly migraine days, irrespective of acute medication overuse. Moreover, the patients reported no significant safety concerns and exhibited good tolerance to treatment. These findings highlight the potential of gepants as a new and effective therapeutic option for patients with CM and/or medication overuse. Gepant use will help improve the management and quality of life of individuals with this debilitating condition.

Treating acute migraine with ubrogepant.

Acute migraine affects millions of people and is one of the most common primary care complaints in the United States. Available first-line abortive treatments are limited and vary in efficacy. Newer medications such as calcitonin gene-related peptide (CGRP) receptor antagonists may be a useful alternative. This article describes the use of ubrogepant, a new CGRP receptor antagonist, in a patient with contraindications to traditional medications used for acute migraine.

The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats.

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic and frequent episodic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab that underlie these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion, as well as the ratio of trigeminal ganglion neurons which are immunoreactive to CGRP and CGRP receptor components, 1-10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons which were immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction in CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.

The development and optimisation of an HPLC-based in vitro serum stability assay for a calcitonin gene-related peptide receptor antagonist peptide.

Evaluation of the stability of peptide drug candidates in biological fluids, such as blood serum, is of high importance during the lead optimisation phase. Here, we describe the optimisation and validation of a method for the evaluation of the stability of a lead calcitonin gene-related peptide antagonist peptide (P006) in blood serum. After initially determining appropriate peptide and human serum concentrations and selection of the quenching reagent, the HPLC method optimisation used two experimental designs, Plackett-Burman design and Taguchi design. The analytical method was validated as complying with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. The optimised method allowed the successful resolution of the parent peptide from its metabolites using RP-HPLC and identification of the major metabolites of P006 by mass spectrometry. This paradigm may be widely adopted as a robust early-stage platform for screening peptide stability to rule out candidates with low in vitro stability, which would likely translate into poor in vivo pharmacokinetics.

Meta-regression to explain the placebo effects in clinical trials of anti-CGRP monoclonal antibodies for migraine prevention

Background: Commonly used methods of comparison (e.g. network meta-analyses) require common comparator(s) across trials, such as placebo in placebo-controlled trials. Recent literature indicates that route of administration differences across placebo arms of clinical trials in pain disorders may contribute to differences in placebo effect.Methods: We conducted a meta-regression on placebo data from pivotal clinical trials of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies for migraine prevention to quantify the impact of route of administration, migraine type (episodic/chronic), and number of prior treatment failures on placebo reduction in monthly migraine days (MMDs) across weeks 1–12 of treatment. A systematic literature review of Embase, MEDLINE, the Cochrane Library, and grey literature conducted in June 2021 identified 14 relevant, randomized placebo-controlled trials for analysis.Results: After testing models with different covariates, a meta-regression was fitted to the extracted placebo data with the covariates of route of administration, migraine type, and proportion of patients with ≥2 prior preventive treatment failures. An intravenous route of administration for the placebo arm was a predictor for higher MMD reduction. Predictors of lower MMD reduction were migraine type (episodic migraine) and a higher proportion of patients having ≥2 failed preventive treatments.Conclusions: The efficacy of intravenous anti-CGRP monoclonal antibodies are likely underestimated, and differences in the route of administration of placebo may necessitate use of alternative methods that do not assume the presence of a common comparator when comparing anti-CGRP monoclonal antibodies in migraine prevention. Further research into the contextual effects of the placebo effect is warranted.

Identification of novel signal of Raynaud’s phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches

ABSTRACT Background Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine. Aim The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches. Research design and methods The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc. Results The PRR ≥ 2 with a linked chi-square value ≥ 4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2, indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways. Conclusion The RP is recognized as a novel signal with all CGRP antagonists.