***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Calcitonin gene-related peptide ( CGRP ) is a vali date d target for the treatment of episodic migraine . Here we assess the safety , tolerability , and efficacy of TEV-48125 , a monoclonal anti-CGRP antibody , in the preventive treatment of high-frequency episodic migraine . METHODS In this multicentre , r and omised , double-blind , placebo-controlled , phase 2b study , we enrolled men and women ( aged 18 - 65 years ) from 62 sites in the USA who had migraine headaches 8 - 14 days per month . Using a r and omisation list generated by a central computerised system and an interactive web response system , we r and omly assigned patients ( 1:1:1 ; stratified by sex and use of concomitant preventive drugs ) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125 , 675 mg TEV-48125 , or placebo . Investigators , patients , and the funder were blinded to treatment allocation . Patients reported headache information daily using an electronic diary . Primary endpoints were change from baseline in migraine days during the third treatment cycle ( weeks 9 - 12 ) and safety and tolerability . The secondary endpoint was change relative to baseline in headache-days during weeks 9 - 12 . Efficacy endpoints were analysed for the intention-to-treat population . Safety and tolerability were analysed using descriptive statistics . This trial is registered at Clinical Trials.gov , number NCT02025556 . FINDINGS Between Jan 8 , 2014 , and Oct 15 , 2014 , we enrolled 297 participants : 104 were r and omly assigned to receive placebo  , 95 to receive 225 mg TEV-48125 , and 96 to receive 675 mg TEV-48125 . The least square mean ( LSM ) change in number of migraine-days from baseline to weeks 9 - 12 was -3.46 days ( SD 5.40 ) in the placebo group , -6.27 days ( 5.38 ) in the 225 mg dose group , and -6.09 days ( 5.22 ) in the 675 mg dose group . The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days ( 95 % CI -4.07 to -1.55 ; p<0.0001 ) , whereas the difference between the placebo and 675 mg dose group was -2.64 days ( -3.90 to -1.38 ; p<0.0001 ) . LSM differences in the reduction of headache-days were -2.63 days ( -3.91 to -1.34 ; p<0.0001 ) between the placebo group and 225 mg dose group and -2.58 days ( -3.87 to 1.30 ; p < 0.0001 ) between the placebo group and the 675 mg dose group . Adverse events occurred in 58 ( 56 % ) patients in the placebo group , 44 ( 46 % ) patients in the 225 mg dose group , and 57 ( 59 % ) patients in the 675 mg dose group ; moderate or severe adverse events were reported for 29 ( 27 % ) patients , 24 ( 25 % ) patients , and 26 ( 27 % ) patients , respectively . INTERPRETATION TEV-48125 , at doses of 225 mg and 675 mg given once every 28 days for 12 weeks , was safe , well tolerated , and effective as a preventive treatment of high-frequency episodic migraine , thus supporting advancement of the clinical development programme to phase 3 clinical trials . FUNDING Teva Pharmaceuticals Objectives : This is the second of a pair of studies design ed to evaluate the efficacy and safety of onabotulinumtoxinA ( BOTOX ® ) for prophylaxis of headaches in adults with chronic migraine . Methods : PREEMPT 2 was a phase 3 study , with a 24-week , double-blind , placebo-controlled phase , followed by a 32-week , open-label phase . Subjects were r and omized ( 1:1 ) to injections of onabotulinumtoxinA ( 155U–195U ; n = 347 ) or placebo ( n = 358 ) every 12 weeks for two cycles . The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21–24 post-treatment . Results : OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint , frequency of headache days per 28 days relative to baseline ( −9.0 onabotulinumtoxinA/−6.7 placebo , p < .001 ) . OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons . OnabotulinumtoxinA was safe and well tolerated , with few treatment-related adverse events . Few patients ( 3.5 % onabotulinumtoxinA/1.4 % placebo ) discontinued due to adverse events . Conclusions : The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine . Repeated onabotulinumtoxinA treatments were safe and well tolerated BACKGROUND Benefits of calcitonin-gene related peptide ( CGRP ) inhibition have not been established in chronic migraine . Here we assess the safety , tolerability , and efficacy of two doses of TEV-48125 , a monoclonal anti-CGRP antibody , in the preventive treatment of chronic migraine . METHODS In this multicentre , r and omised , double-blind , double-dummy , placebo-controlled , parallel-group phase 2b study , we enrolled men and women ( aged 18 - 65 years ) from 62 sites in the USA who had chronic migraine . Using a r and omisation list generated by a central computerised system and an interactive web response system , we r and omly assigned patients ( 1:1:1 , stratified by sex and use of concomitant preventive drugs ) to three 28-day treatment cycles of subcutaneous TEV-48125 675/225 mg ( 675 mg in the first treatment cycle and 225 mg in the second and third treatment cycles ) , TEV-48125 900 mg ( 900 mg in all three treatment cycles ) , or placebo . Investigators , patients , and the funder were blinded to treatment allocation . Daily headache information was captured using an electronic diary . Primary endpoints were change from baseline in the number of headache-hours during the third treatment cycle ( weeks 9 - 12 ) and safety and tolerability during the study . Secondary endpoint was change in the number of moderate or severe headache-days in weeks 9 - 12 relative to baseline . Efficacy endpoints were analysed for the intention-to-treat population . Safety and tolerability were analysed using descriptive statistics . This trial is registered with Clinical Trials.gov , number , NCT02021773 . FINDINGS Between Jan 8 , 2014 , and Aug 27 , 2014 , we enrolled 264 participants : 89 were r and omly assigned to receive placebo , 88 to receive 675/225 mg TEV-48125 , and 87 to receive 900 mg TEV-48125 . The mean change from baseline in number of headache-hours during weeks 9 - 12 was -59.84 h ( SD 80.38 ) in the 675/225 mg group and -67.51 h ( 79.37 ) in the 900 mg group , compared with -37.10 h ( 79.44 ) in the placebo group . The least square mean difference in the reduction of headache-hours between the placebo and 675/225 mg dose groups was -22.74 h ( 95 % CI -44.28 to -1.21 ; p=0.0386 ) , whereas the difference between placebo and 900 mg dose groups was -30.41 h ( -51.88 to -8.95 ; p=0.0057 ) . Adverse events were reported by 36 ( 40 % ) patients in the placebo group , 47 ( 53 % ) patients in the 675/225 mg dose group , and 41 ( 47 % ) patients in the 900 mg dose group , whereas treatment-related adverse events were recorded in 15 ( 17 % ) patients , 25 ( 29 % ) patients , and 28 ( 32 % ) patients , respectively . The most common adverse events were mild injection-site pain and pruritus . Four ( 1 % ) patients had serious non-treatment-related adverse events ( one patient in the placebo group , one patient in the 675/225 mg group , and two patients in the 900 mg group ) ; no treatment-related adverse events were serious and there were no relevant changes in blood pressure or other vital signs . INTERPRETATION TEV-48125 given by subcutaneous injection every 28 days seems to be tolerable and effective , thus supporting the further development of TEV-48125 for the preventive treatment of chronic migraine in a phase 3 trial . FUNDING Teva Pharmaceuticals BACKGROUND Fremanezumab ( formerly TEV-48125 ) is a monoclonal antibody directed against calcitonin-gene-related peptide ( CGRP ) , a vali date d target for migraine preventive therapy . In two previous phase 2 studies , fremanezumab administered once every 28 days for 12 weeks was found to be effective and safe as a preventive treatment for patients suffering from episodic migraine ( EM ) and chronic migraine ( CM ) . OBJECTIVE To evaluate the efficacy and safety of fremanezumab as an add-on preventive therapy in individuals with EM and CM who are on stable doses of preventive migraine medications . METHODS Two r and omized placebo-controlled  studies tested once-monthly subcutaneous injections of various dosing regimens of fremanezumab versus placebo in EM and CM . Headache information was captured daily using an electronic headache diary . For these post hoc analyses , data were pooled from patients who were on stable preventive medications and taking fremanezumab doses of 225 mg or 675/225 mg , or placebo . RESULTS The sample consisted of 133 patients , ( 67 fremanezumab and 66 placebo ) .  Total reduction in migraine days for the duration of the study was 12.4 for fremanezumab and 7.4 for placebo ( P = .0321 ) . There were also decreases in moderate/severe headache days ( 12.5 vs 7.1 , P = .0058 ) , and days using acute medication for headaches relative to placebo ( 11.6 vs 7.5 , P = .0414 ) . Treatment emergent adverse events were generally mild and transient , and no serious adverse events were considered to be treatment-related by the site investigators . CONCLUSIONS The findings from these post hoc analyses suggest that fremanezumab is a safe and effective add-on treatment for migraine patients being concomitantly treated with other migraine preventive medications . Trials are registered at Clinical trials.gov NCT02025556 and NCT02021773 Objective : To assess long-term safety and efficacy of anti – calcitonin gene-related peptide receptor erenumab in patients with episodic migraine ( EM ) . Methods : Patients enrolled in a 12-week , double-blind , placebo-controlled  clinical trial ( NCT01952574 ) who continued in an open-label extension ( OLE ) study will receive erenumab 70 mg every 4 weeks for up to 5 years . This preplanned interim analysis , conducted after all participants had completed the 1-year open-label follow-up , evaluated changes in monthly migraine days ( MMD ) , achievement of ≥50 % , ≥75 % , and 100 % reductions , Headache Impact Test ( HIT-6 ) score , Migraine-Specific Quality of Life ( MSQ ) , Migraine Disability Assessment ( MIDAS ) , and safety . Data reported as observed without imputation for missing data . Results : Of 472 patients enrolled in the parent study , 383 continued in the OLE with a median exposure to erenumab of 575 days ( range 28–822 days ) . Mean ( SD ) MMD were 8.8 ( 2.6 ) at parent study baseline , 6.3 ( 4.2 ) at week 12 ( beginning of OLE ) , and 3.7 ( 4.0 ) at week 64 ( mean change from baseline [ reduction ] of 5.0 days ) . At week 64 , 65 % , 42 % , and 26 % achieved ≥50 % , ≥75 % , and 100 % reduction in MMD , respectively . Mean HIT-6 scores were 60.2 ( 6.3 ) at bas 
    Output:
    
Results We found low to high quality of evidence to recommend eptinezumab , erenumab , fremanezumab , and galcanezumab in patients with episodic migraine  and medium to high quality of evidence to recommend erenumab , fremanezumab , and galcanezumab in patients with chronic migraine .
For several clinical questions , there was not enough evidence to provide recommendations using the GRADE approach and recommendations relied on experts ’ opinion .
Conclusion Monoclonal antibodies acting on the calcitonin gene-related peptide are new drugs which can be recommended for migraine prevention .