Triptans for the Treatment of Acute Migraines in Adults: A Systematic Review and Network Meta- Analysis (ONLINE APPENDICES) George Wells, Shannon Kelly, Chris Cameron, Meghan Murphy, Shu-Ching Hsieh, Ahmed Kotb, Joan Peterson, Li Chen, Vijay Shukla, Becky Skidmore February 2014 30 Bond Street, Toronto ON, M5B 1W8 www.odprn.ca [email protected] 2 APPENDICES Appendix A: Review of Previous Evidence Syntheses Author, Interventions Comparators Studies Major Conclusion(s) Notes Publication Date Included (n) Thorlund et al. Oral triptan Oral triptan or 74 Efficacy: Triptans appear to Industry-funded 2013(11) placebo offer differing treatment Only included: effects. Eletriptan Double blind RCTs consistently has the highest Oral formulations odds of producing headache Excluded: relief at 2 hours, freedom Patients with history from pain at 2 hours, of treatment- sustained headache relief at resistant migraines 24 hours, and sustained (i.e. previous poor freedom from pain at 24 response to a hours. triptan) Had other clinical Rizatriptan, zolmitriptan, and significant high-dose (100 mg) Illnesses sumatriptan also appear effective at two hours, No menstrual whereas only zolmitriptan migraines and high-dose sumatriptan No safety appear to maintain their efficacy at 24 hours. Ontario Drug Policy Research Network Ontario Drug Policy Research Network 3 Worthington Triptans Varied by Twelve acute medications Limited literature 2013 (1) comparison, received a strong search with limited mix of recommendation for use in transparency of SR/MA and acute migraine therapy methods, no RCT (almotriptan, eletriptan, information frovatriptan, naratriptan, scientist used in the rizatriptan, sumatriptan, literature search zolmitriptan, ASA, ibuprofen, conduct, unsure of naproxen sodium, diclofenac data synthesis potassium, and methods, primary acetaminophen). Four RCTs used only received a weak where existing SR or recommendation for use MA was not (dihydroergotamine, available (no ergotamine, codeine- indication of containing combination whether the quality analgesics, and tramadol- of the SR/MAs used containing combination was assessed), no analgesics). Three of these indirect were not recommended for comparisons routine use (ergotamine, and conducted. codeine- and tramadol- containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital- containing medications. NICE, Triptan Triptan, 19 Offer combination therapy Included 2013(7) antiemetics, with an oral triptan and an adolescents 12 to aspirin, NSAIDs, NSAID, or an oral triptan and 18, Placebo not opioids, acetaminophen, for the included as acetaminophen, acute treatment of migraine, comparator. triptans, ergots taking into account the and person's preference, NMA limited corticosteroids comorbidities and risk of outcomes to: adverse events. For young headache response people aged 12–17 years up to 2 hours; consider a nasal triptan in freedom from pain preference to an oral triptan. up to 2 hours; For women and girls with sustained headache predictable menstrual- response at 24 related migraine that do not hours and sustained respond adequately to freedom from pain standard acute treatment, at 24 hours, change consider treatment with in patient reported frovatriptan (2.5 mg twice a migraine days. day) or zolmitriptans (2.5 mg twice or three times a day) Triptans generally on the days migraine is studied as a class in expected. the NMA, only separately in a few analyses Ontario Drug Policy Research Network Ontario Drug Policy Research Network 4 Asseburg et al. Oral Triptan at Oral triptan at 56 Efficacy and safety: The Update of a 2012(8) listed dosing listed dosing or highest probability of 2-hour previous review placebo pain-free was estimated for (Ferrari 2000) eletriptan 40 mg and the Two databases lowest probability of searched recurrence was estimated for naratriptan 2.5 mg. The probability of achieving sustained pain-free and no adverse events was estimated to be highest with eletriptan 40 mg. Cochrane Various – Head to head Triptans studied (numerous)(137- single drug with similar or individually 150) formulation placebo or combination Helfand 2009(9, Triptans (oral, Triptans (oral, 98 There is no consistent NMA only 10) nasal, and nasal, and evidence that one triptan has conducted where injectable injectable or any particular advantage or there were no head- placebo disadvantage over another in to-head any subgroup based on age, comparisons and race, gender, prophylactic where there was a treatment, or menstruation- common associated migraine. intervention across studies. Otherwise standard meta- analysis and qualitative review done. Ontario Drug Policy Research Network Ontario Drug Policy Research Network 5 Appendix B: Detailed Literature Search Strategy Triptans – Acute Migraines – Final Strategies 2013 Oct 6 Database: Embase Classic+Embase <1947 to 2013 October 04>, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Present> Search Strategy: -------------------------------------------------------------------------------- 1 exp Migraine Disorders/ (66228) 2 (migrain* or migran*).tw. (89392) 3 (anti-migrain* or antimigrain* or anti-migran* or antimigran*).tw. (2360) 4 sick headache*.tw. (31) 5 or/1-4 (106437) 6 exp Tryptamines/ (86272) 7 (tryptamin* or tryptomin* or triptan* or indolylethylamine* or NSC 73938 or NSC73938).tw. (10838) 8 ("BRN 0125513" or CCRIS 8959 or EINECS 200-510-5 or Indol-3-ethylamine or UNII-422ZU9N5TV).tw. (0) 9 Tryptamines.rn. (4631) 10 (almotriptan* or Almogran or Almotrex or Amignul or Axert or PNU 180638E or PNU-180638E or UNII- PJP312605E).tw. (681) 11 almotriptan.rn. (1149) 12 (eletriptan* or Relpax or Relert or Relepax or "UK 116044" or "UK 116,044" or "UK-116044" or "UK-116,044" or UNII-22QOO9B8KI).tw. (686) 13 eletriptan.rn. (1281) 14 (frovatriptan* or Allegro or Frova or Frovelan or Migard or Miguard or SB 209509 or VML-251 or VML251).tw. (927) 15 frovatriptan.rn. (872) 16 (naratriptan* or Amerge or Colatan or Naragran or Naramig or UNII-QX3KXL1ZA2).tw. (841) 17 naratriptan.rn. (1619) 18 (rizatriptan* or Risatriptan* or "L 705,126" or "L 705126" or "L-705,126" or "L-705126" or Maxalt or "MK 0462" or MK 462 or MK-0462 or MK-462 or rizalief or rizalt or rizaliv or UNII-51086HBW8G).tw. (1299) 19 rizatriptan.rn. (2190) 20 (sumatriptan* or Arcoiran or Alsuma or BRN 6930870 or Diletan or Dolmigral or GR 43175 or GR 43175X or GR-43175 or HSDB 7742 or Imigran* or Imiject or Imitrex or micranil or Migril or Novelian or Sumigrene or Suminat or Sumatran or Sumatriptanum or Sumax or UNII-8R78F6L9VO or Zecuity).tw. (6824) 21 sumatriptan.rn. (8795) 22 (Zolmitriptan* or AscoTop or Flezol or Rapimelt or UNII-2FS66TH3YW or Zolmitriptan or Zomig or Zomig-ZMT or Zomigon or Zomigoro).tw. (1407) 23 Zolmitriptan.rn. (2644) 24 (Treximet or Trexima).tw. (60) 25 or/6-24 (102640) 26 5 and 25 (11117) 27 randomized controlled trial.pt. (387867) 28 exp randomized controlled trials as topic/ (142502) 29 random allocation/ (145233) 30 double-blind method/ or single-blind method/ (289667) 31 Placebos/ (277057) 32 (random* or RCT$1 or placebo*).tw. (1760512) 33 ((singl* or doubl* or trebl* or tripl*) and (mask* or blind* or dumm*)).tw. (332772) 34 or/27-33 (2166102) 35 26 and 34 (2796) 36 adult.mp. (9410610) Ontario Drug Policy Research Network Ontario Drug Policy Research Network 6 37 middle aged.sh. (4500001) 38 age$.tw. (5885873) 39 or/36-38 (14388970) 40 35 and 39 (1651) 41 exp Animals/ not (exp Animals/ and Humans/) (8923948) 42 40 not 41 (1647) 43 (comment or editorial or interview or letter or news).pt. (2770847) 44 42 not 43 (1638) 45 limit 44 to english language (1599) 46 45 use prmz (705) 47 exp migraine/ (66228) 48 (migrain* or migran*).tw. (89392) 49 (anti-migrain* or antimigrain* or anti-migran* or antimigran*).tw. (2360) 50 sick headache*.tw. (31) 51 or/47-50 (106437) 52 tryptamine derivative/ (2624) 53 triptan derivative/ (1999) 54 (tryptamin* or tryptomin* or triptan* or indolylethylamine* or NSC 73938 or NSC73938).tw,tn. (10838) 55 ("BRN 0125513" or CCRIS 8959 or EINECS 200-510-5 or Indol-3-ethylamine or UNII-422ZU9N5TV).tw,tn. (0) 56 61-54-1.rn. (2370) 57 almotriptan/ (997) 58 (almotriptan* or Almogran or Almotrex or Amignul or Axert or PNU 180638E or PNU-180638E or UNII- PJP312605E).tw,tn. (681) 59 154323-57-6.rn. (986) 60 eletriptan/ (1156) 61 (eletriptan* or Relpax or Relert or Relepax or "UK 116044" or "UK 116,044" or "UK-116044" or "UK-116,044" or UNII-22QOO9B8KI).tw,tn. (686) 62 143322-58-1.rn. (1135) 63 frovatriptan/ (792) 64 (frovatriptan* or Allegro or Frova or Frovelan or Migard or Miguard or SB 209509 or VML-251 or VML251).tw,tn. (927) 65 158747-02-5.rn. (764) 66 naratriptan/ (1470) 67 (naratriptan* or Amerge or Colatan or Naragran or Naramig or UNII-QX3KXL1ZA2).tw,tn. (841) 68 121679-13-8.rn. (1619) 69 rizatriptan/ (1928) 70 (rizatriptan* or Risatriptan* or "L 705,126" or "L 705126" or "L-705,126" or "L-705126" or Maxalt or "MK 0462" or MK 462 or MK-0462 or MK-462 or rizalief or rizalt or rizaliv or UNII-51086HBW8G).tw,tn. (1299) 71 144034-80-0.rn. (1881) 72 sumatriptan/ (8967) 73 (sumatriptan* or Arcoiran or Alsuma or BRN 6930870 or Diletan or Dolmigral or GR 43175 or GR 43175X or GR-43175 or HSDB 7742 or Imigran* or Imiject or Imitrex or micranil or Migril or Novelian or Sumigrene or Suminat or Sumatran or Sumatriptanum or Sumax or UNII-8R78F6L9VO or Zecuity).tw,tn. (6824) 74 103628-46-2.rn. (8795) 75 Zolmitriptan/ (2314) 76 (Zolmitriptan* or AscoTop or Flezol or Rapimelt or UNII-2FS66TH3YW or Zolmitriptan or Zomig or Zomig-ZMT or Zomigon or Zomigoro).tw,tn. (1407) 77 139264-17-8.rn. (2644) 78 naproxen plus sumatriptan succinate/ (23) 79 (Treximet or Trexima).tw,tn. (60) 80 811794-26-0.rn. (0) 81 or/52-80 (25720) Ontario Drug Policy Research Network Ontario Drug Policy Research Network 7 82 51 and 81 (10907) 83 randomized controlled trial/ (747726) 84 "randomized controlled trial (topic)"/ (39581) 85 Randomization/ (145233) 86 double blind procedure/ or single blind procedure/ or placebo/ (330971) 87 (random* or RCT$1 or placebo*).tw.