Would your patient benefit from a monoclonal antibody?

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doi:doi: 10.12788/jfp.0481

Applied Evidence

Would your patient benefit from a monoclonal antibody?

J Fam Pract. 2022 October;71(8):E1-E8 | doi: 10.12788/jfp.0481

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References

1. Rui P, Okeyode T. National Ambulatory Medical Care Survey: 2016 national summary tables. National Center for Health Statistics. Accessed June 15, 2022. www.cdc.gov/nchs/data/ahcd/namcs_summary/2016_namcs_web_tables.pdf

2. IDBS. The future of biologics drug development is today. June 27, 2018. Accessed June 15, 2022. www.idbs.com/blog/2018/06/the-future-of-biologics-drug-development-is-today/

3. Antibody therapeutics approved or in regulatory review in the EU or US. Antibody Society. Accessed June 15, 2022. www.antibodysociety.org/resources/approved-antibodies/

4. FDA. Code of Federal Regulations, Title 21, Chapter I, Subchapter F biologics. March 29, 2022. Accessed June 15, 2022. www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=600.3

5. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495-497. doi: 10.1038/256495a0

6. Raejewsky K. The advent and rise of monoclonal antibodies. Nature. November 4, 2019. Accessed June 15, 2022. www.nature.com/articles/d41586-019-02840-w

7. Flovent. Prescribing information. GlaxoSmithKline; 2010. Accessed June 15, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2010/021433s015lbl.pdf

8. NLM. National Center for Biotechnology Information. PubChem. Method for the preparation of fluticasone and related 17beta-carbothioic esters using a novel carbothioic acid synthesis and novel purification methods. Accessed June 15, 2022. pubchem.ncbi.nlm.nih.gov/patent/WO-0162722-A2

9. Nucala. Prescribing information. GlaxoSmithKline; 2019. Accessed June 15, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2019/761122s000lbl.pdf

10. Argyriou AA, Kalofonos HP. Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. Mol Med. 2009;15:183-191. doi: 10.2119/molmed.2009.00007

11. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84:548-558. doi: 10.1038/clpt.2008.170

12. Zahavi D, AlDeghaither D, O’Connell A, et al. Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy. Antib Ther. 2018;1:7-12. doi: 10.1093/abt/tby002

13. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014:CD003559. doi: 10.1002/14651858.CD003559.pub4

14. Farne HA, Wilson A, Powell C, et al. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017;9:CD010834. doi: 10.1002/14651858.CD010834.pub3

15. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486-2496. doi: 10.1056/NEJMoa1804092

16. GINA. Global strategy for asthma management and prevention. 2022 Difficult-to-treat and severe asthma guide—slide set. Accessed June 23, 2022. https://ginasthma.org/severeasthma/

17. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207. doi: 10.1056/NEJMoa1403290

18. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197. doi: 10.1056/NEJMoa1403291

19. Adbry. Prescribing information. Leo Pharma Inc; 2021. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761180Orig1s000lbl.pdf

20. Dupixent. Prescribing information. Regeneron Pharmaceuticals; 2022. Accessed October 5, 2022. https://www.regeneron.com/downloads/dupixent_fpi.pdf

21. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335-2348. doi: 10.1056/NEJMoa1610020

22. Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389:2287-2303. doi: 10.1016/s0140-6736(17)31191-1

23. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71:327-349. doi: 10.1016/j.jaad.2014.03.030

24. Evkeeza. Prescribing information. Regeneron Pharmaceuticals; 2021. Accessed June 24, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761181s000lbl.pdf

25. Repatha. Prescribing information. Amgen; 2015. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2017/125522s014lbl.pdf

26. Praluent. Prescribing information. Sanofi Aventis and Regeneron Pharmaceuticals. 2015. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2017/125559s002lbl.pdf

27. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-1722. doi: 10.1056/NEJMoa1615664

28. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097-2107. doi:10.1056/NEJMoa1801174

29. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2019;73:e285-e350. doi: 10.1016/j.jacc.2018.11.003

30. Prolia. Prescribing information. Amgen; 2010. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2013/125320s094lbl.pdf

31. Evenity. Prescribing information. Amgen; 2019. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2019/761062s000lbl.pdf

32. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756-765. doi: 10.1056/NEJMoa0809493

33. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532-1543. doi: 10.1056/NEJMoa1607948

34. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377:1417-1427. doi: 10.1056/NEJMoa1708322

35. Aimovig. Prescribing information. Amgen; 2018. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2018/761077s000lbl.pdf

36. Vyepti. Prescribing information. Lundbeck Seattle BioPharmaceuticals; 2020. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2020/761119s000lbl.pdf

37. Ajovy. Prescribing information. Teva Pharmaceuticals; 2018. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2018/761089s000lbl.pdf

38. Emgality. Prescribing information. Eli Lilly and Co.; 2018. Accessed June 24, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2018/761063s000lbl.pdf

39. Edvinsson L, Haanes KA, Warfvinge K, et al. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018;14:338-350. doi: 10.1038/s41582-018-0003-1

40. Vandervorst F. Van Deun L, Van Dycke A, et al. CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs. J Headache Pain. 2021;22:128. doi: 10.1186/s10194-021-01335-2

41. Saely S, Croteau D, Jawidzik L, et al. Hypertension: a new safety risk for patients treated with erenumab. Headache. 2021;61:202-208. doi: 10.1111/head.14051

42. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59:1-18. doi: 10.1111/head.13456

43. Burch R. Headache in pregnancy and the puerperium. Neurol Clin. 2019;37:31-51. doi: 10.1016/j.ncl.2018.09.004

44. Burch R. Epidemiology and treatment of menstrual migraine and migraine during pregnancy and lactation: a narrative review. Headache. 2020;60:200-216. doi: 10.1111/head.13665

45. Lexi-Comp. Lexi-drug database. Accessed April 4, 2022. https://online.lexi.com/lco/action/login

46. Walker N. Biologics: driving force in pharma. Pharma’s Almanac. June 5, 2017. Accessed June 15, 2020. www.pharmasalmanac.com/articles/biologics-driving-force-in-pharma

In another study, romosozumab 210 mg SC was compared with alendronate 70 mg weekly, followed by alendronate 70 mg weekly in both groups. Over the first 12 months, patients treated with romosozumab saw a significant reduction in the incidence of new vertebral fractures (4% vs 6.3%; RR = 0.63, P < .003; NNT = 44). Patients treated with romosozumab with alendronate added for another 12 months also saw a significant reduction in new incidence of vertebral fractures (6.2% vs 11.9%; RR = 0.52; P < .001; NNT = 18).³⁴ There was a higher risk of cardiovascular events among patients receiving romosozumab compared with those treated with alendronate, so romosozumab should not be used in individuals who have had an MI or stroke within the previous year.³⁴ Denosumab and romosozumab offer an advantage over some bisphosphonates in that they require less frequent dosing and can be used in patients with renal impairment (creatinine clearance < 35 mL/min, in which zoledronic acid is contraindicated and alendronate is not recommended; < 30 mL/min, in which risedronate and ibandronate are not recommended).

Migraine prevention

Four calcitonin gene-related peptide (CGRP) antagonists have been approved for migraine prevention: erenumab (Aimovig),³⁵ eptinezumab (Vyepti),³⁶ fremanezumab (Ajovy),³⁷ and galcanezumab (Emgality).³⁸ CGRP is released at areas in and around the brain, causing vasodilation and inflammation that is thought to be the major causative factor for migraine headaches.³⁹

Erenumab, fremanezumab, and galcanezumab are all available in subcutaneous autoinjectors (or syringe with fremanezumab). Eptinezumab is an intravenous (IV) infusion given every 3 months.

Erenumab is available in both 70-mg and 140-mg dosing options. Fremanezumab can be given as 225 mg monthly or 675 mg quarterly. Galcanezumab has an initial loading dose of 240 mg followed by 120 mg given monthly. Erenumab targets the CGRP receptor; the others target the CGRP ligand. Eptinezumab has 100% bioavailability and reaches maximum serum concentration sooner than the other antagonists (due to its route of administration), but it must be given in an infusion center. Few insurers approve the use of eptinezumab unless a trial of least 1 of the monthly injectables has failed.

There are no head-to-head studies of the medications in this class. Additionally, differing study designs, definitions, statistical analyses, endpoints, and responder-rate calculations make it challenging to compare them directly against one another. At the very least, all of the CGRP MAbs have efficacy comparable to conventional preventive migraine medications such as propranolol, amitriptyline, and topiramate.⁴⁰

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