New drugs pro­vid­ing hope for treat­ment of mi­graines

The Island Packet - - The Long Read - BY SARAH VANDER SCHAAFF Wash­ing­ton Post

Nancy Baum Lip­sitz re­mem­bers the night the pain be­gan. She’d had a glass of white wine with a friend and went to bed with a ter­ri­ble headache. The next day, she still felt hor­ri­ble, the be­gin­ning of what she called a “rolling tide” of near con­stant mi­graines and lower level headaches.

For three years she dealt with the symp­toms. Some­times she got tun­nel vi­sion, or a vis­ual aura, a warn­ing that a big headache was on the way. Those felt like “some­one tak­ing a pick and jab­bing it through my nose and eye,” she said.

Then there was the vom­it­ing, numb­ness and sen­si­tiv­ity to light and noise. Her speech slurred. Less se­vere headaches felt like a “hang­over.” She stopped ex­er­cis­ing, so­cial­iz­ing and over­see­ing her 15-year-old daugh­ter’s home­work, re­ly­ing in­stead on her daugh­ter to take care of her when a mi­graine at­tacked.

“Ev­ery­thing you are as a hu­man be­ing gets stripped away,” Lip­sitz said of what was ul­ti­mately di­ag­nosed as re­frac­tory mi­graine. The one thing she did not give up was her work. As di­rec­tor of anes­the­si­ol­ogy at Carnegie Hill En­doscopy in New York, she knew pa­tients and staff de­pended on her.

Mi­graine, a type of headache dis­or­der that is dis­tin­guished from ten­sion headaches by its pain, fre­quency, and the nau­sea and sen­si­tiv­i­ties Lip­sitz en­dured, af­fects 10 per­cent of the world pop­u­la­tion and 29.5 mil­lion Amer­i­cans, the ma­jor­ity of them women, of­ten dur­ing the prime years of ca­reer and par­ent­hood.

The cost, mea­sured by di­rect health-care ex­penses, lost or poor pro­duc­tiv­ity, and missed fam­ily in­volve­ments, af­fects chil­dren, too. A re­cent study showed in­creased anx­i­ety and de­pres­sion in ado­les­cent chil­dren of par­ents with chronic mi­graine.

For years, treat­ment has been lim­ited and pri­mar­ily ad­dressed symp­toms rather than preven­tion. Mi­graine was thought to be “more of a hys­ter­i­cal woman’s dis­ease and not given the re­spect it re­ally de­serves,” said Su­san Broner, Lip­sitz’s neu­rol­o­gist and med­i­cal di­rec­tor of the Headaches Pro­gram at Weill Cor­nell Medicine/New YorkPres­by­te­rian. Fund­ing for re­search has typ­i­cally been dis­pro­por­tion­ately low com­pared with the dis­ease’s ef­fect.

But new treat­ments, decades in the mak­ing, are giv­ing pa­tients more op­tions to man­age what is now un­der­stood to be a com­plex neu­ro­log­i­cal dis­ease. This year, the Food and Drug Ad­min­is­tra­tion ap­proved three drugs meant to pre­vent mi­graines and those, along with less ex­pen­sive and less in­va­sive tech­niques to stim­u­late the body’s re­sponse to pain through neu­rostim­u­la­tion, are giv­ing headache spe­cial­ists and the pa­tients they treat op­ti­mism.

“The en­tire field is chang­ing,” said Stephen Sil­ber­stein, di­rec­tor of the Headache Cen­ter at Jef­fer­son Health in Philadel­phia. “There is a revo­lu­tion in mi­graine.”

In July, Lip­sitz started monthly in­jec­tions of erenumab-aooe (Ai­movig), one of the three new drugs tar­get­ing the pain trans­mit­ting sig­nal, cal­ci­tonin gene-re­lated pep­tide (CGRP) or its re­cep­tor. Mon­o­clonal an­ti­bod­ies, such as the one in her med­i­ca­tion, work by block­ing CGRP, the chem­i­cal in­volved in mi­graine.

“I see it as be­ing my sav­ior, my hope,” she said. She has had more days of feel­ing good in three re­cent weeks than she had in the pre­vi­ous three years.

The treat­ment has not elim­i­nated all pain. Lip­sitz has not been able to wean off other med­i­ca­tions. But the new ther­apy has given back much of what mi­graines had taken away, es­pe­cially time with her hus­band.

Pre­vent­ing mi­graines with CGRP an­ti­bod­ies opens up a new world, Broner said. “It is the first time we have a med­i­ca­tion de­vel­oped specif­i­cally for the mech­a­nism of mi­graine, which means we are re­ally tar­get­ing the dis­ease state it­self.”

For decades, doc­tors treated mi­graines with ther­a­pies de­vel­oped for other dis­eases, us­ing blood pres­sure med­i­ca­tion, anti-seizure drugs, anti-de­pres­sants and even On­abo­tulinum­tox­inA (Bo­tox). Lip­sitz has been on all of these, find­ing some re­lief but also re­duced ef­fec­tive­ness over time, or side ef­fects and fa­tigue. The non­s­teroidal anti-in­flam­ma­tory drugs she took for break­through pain gave her a bleed­ing ul­cer and kid­ney dam­age.

The new drugs are unique be­cause they not only pre­vent (as op­posed to abort) mi­graine at­tacks but also are well tol­er­ated.

“That’s the key,” said David Dod­ick, a neu­rol­o­gist and headache spe­cial­ist at the Mayo Clinic in Ari­zona. “If I give you some­thing to take and it’s ef­fec­tive but you can’t tol­er­ate the side ef­fects, you’ll stop it.”

The re­cent shift in mi­graine treat­ment comes from a change in un­der­stand­ing what causes them, he said. Mi­graine had pre­vi­ously been con­sid­ered a blood ves­sel prob­lem. It was “re­ally a nerve prob­lem,” he said.

Credit for un­der­stand­ing the role CGRP plays in the brain goes in large part to the Swedish re­searcher, Lars Ed­vins­son, who be­gan his work 30 years ago. In 1990, Ed­vins­son and a col­league, Peter Goadsby, looked for CGRP in pa­tients dur­ing a mi­graine at­tack, tak­ing blood sam­ples from the jugu­lar vein, near the point of re­lease in the brain, in­stead of the arm, where lev­els are di­luted. They showed CGRP was the only neu­ropep­tide re­leased dur­ing the headache phase.

Some of the new an­ti­body drugs - gal­canezumab, (Em­gal­ity), fre­manezumab (Ajovy) and eptinezumab, now in phase 3 clin­i­cal tri­als and ad­min­is­tered as a quar­terly in­fu­sion – tar­get CGRP di­rectly, while erenumab (Ai­movig), tar­gets the CGRP re­cep­tor, the means by which the pro­tein trans­mits pain. Block­ing the re­cep­tor is like putting gum in a lock, Dod­ick said. “You can’t get the key in any­more. You can’t open the door,” he said.

Still, not all peo­ple will re­spond to CGRP-re­lated ther­a­pies. And while clin­i­cal tri­als show few side ef­fects, large pa­tient pop­u­la­tions have yet to be fol­lowed in long-range stud­ies. CGRP is in­volved in other func­tions in­volv­ing the heart and skin, and there is rea­son to still be cau­tious, Broner said.

Neu­rostim­u­la­tion, which uses elec­tri­cal stim­u­la­tion to treat pain, is also giv­ing pa­tients more op­tions, es­pe­cially with the devel­op­ment of non­in­va­sive de­vices or less in­va­sive pro­ce­dures.


New drug treat­ments, decades in the mak­ing, are giv­ing pa­tients more op­tions to man­age mi­graine headaches.

Newspapers in English

Newspapers from USA

© PressReader. All rights reserved.