Study ID	Treatment	Local AEs	Systemic AEs	Serious AEs	Withdrawals
Airaksinen 1993	(1) Ketoprofen gel 2 x 5 g (125 mg) daily, n = 29 (2) Placebo gel, n = 27	(1) 5/29 (2) 4/27	(1) 1/29 (nausea after paracetamol) (2) 0/27	None	AE: none Other: none reported
Ăkermark 1990	(1) Indomethacin spray 1% (Elmetacin), 3‐5 x 0.5‐1.5 mL daily, n = 23 (2) Indomethacin capsules, 3 x 25 mg daily, n = 23 (3) Placebo spray and capsules, n = 24	(1) 4/22 (2) 0/22 (3) 0/24	No usable data ‐ reported for events not participants	None reported	AE: (1) 1, (2) 1, (3) 0 Lost to follow‐up: (1) 1, (2) 2, (3) 3
Aoki 1984	(1) Piroxicam gel 5%, 3 or 4 x 1 g daily, n = 84 (2) Indomethacin gel 1%, 3 or 4 x 1 g daily, n = 84 (3) Placebo gel, n = 84	(1) 1/79 (2) 2/70 (3) 2/74	None	None reported	AE: none 23 excluded for protocol violations: (1) 7, (2) 7, (3) 9 26 withdrew for reasons unrelated to treatment: (1) 5, (2) 13, (3) 8
Auclair 1989	(1) Niflumic acid gel 2.5%, 3 x 5 g daily, n = 117 (2) Placebo gel, n = 110	All AEs (1) 5/123 (2) 6/116 Most commonly cutaneous eruptions	No usable data	None reported	AE: (1) 1/123, (2) 0/116 26 excluded from efficacy analysis for not meeting entry criteria and protocol violations
Billigmann 1996	(1) Ibuprofen microgel 5% 3 x 200 mg daily, n = 80 (2) Placebo gel, n = 80	(1) 11/80 (2) 4/80	None reported	None reported	AE: (1) 2/80 (allergic rash, dermatitis) No reason given: (1) 3/80, (2) 5/80 Symptom‐free: (1) 1/80, (2) 1/80
Campbell 1994	(1) Ibuprofen cream 5% (Proflex) 4 x 4" daily, n = 26 (2) Placebo cream, n = 25	No data	(1) 1/26 (headache) (2) 0/25	No data	AE: none Exclusions 49: 3 presented late, 2 missing forms, 1 appeared twice, 43 did not return diaries
Chatterjee 1977	(1) Benzydamine HCl cream 3% 3 x daily, n = 25 (2) Placebo cream, n = 25	None	None	None	AE: none 1 participant lost to follow‐up (group not reported)
Costantino 2011	(1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 142 (2) DHEP plaster (Flector) x 1 daily, n = 146 (3) Placebo plaster, n = 142	Possibly or probably drug‐related (1) 2/142 (2) 1/145 (3) 6/142 All mild and gone by 14 days, except 1 (moderate) in placebo group	Not reported No systemic GI events	None	AE: none Other: (1) 0/142 (2) 2/146 (protocol deviation, lost to follow‐up) (3) 2/142 (lost to follow‐up)
Coudreuse 2010	(1) DHEP‐heparin plaster (Flectorparin), n = 120 (2) Placebo, n = 120	(1) 1/117 (2) 7/116 All AEs mild or moderate, resolved spontaneously	(1) 1/117 (2) 0/116	None	AE: (1) 1/117 (increased oedema) (2) 0/116 Other: (1) 6/117 (recovery 3, no reason 3) (2) 3/116 (recovery 1, no reason 2)
Curioni 1985	(1) Ibuproxam, n = 20 (2) Ketoprofen, n = 20 (3) Etofenamate, n = 20	None	None	None	AE: none Other: none
Diebshlag 1990	(1) Ketorolac gel 2% 3 x 3 g daily, n = 13 (2) Etofenamate gel 5% 3 x 3 g daily, n = 12 (3) Placebo gel, n = 12	(1) 1/13 (2) 1/12 (3) 0/12	None	None	AE: none 1 ketorolac participant did not attend 15 day follow‐up due to car accident
Dreiser 1988	(1) Ibuprofen cream 5%, 3 x 4 cm daily, n = 32 (3 x 10 cm for large joints) (2) Placebo cream, n = 32	No usable data	None	Not reported	AE: none 4 placebo participants lost to follow‐up
Dreiser 1989	(1) Ketoprofen gel 2.5%, 2 x 5 cm daily, n = 30 (2) Placebo gel, n = 30	(1) 0/30 (2) 2/30	None	None reported	AE: (2) 2/30 (intolerance) LoE: (1) 1/30, (2) 1/30
Dreiser 1990	(1) Niflumic acid gel 2.5%, 3 x 5 g daily, n = 30 (2) Placebo gel, n = 30	(1) 0/30 (2) 3/30	None	None	AE: (2) 1/30 (erythema) Exclusion: 1 from (2) from efficacy analysis for inadequate baseline pain
Dreiser 1994	(1) Flurbiprofen plaster 2 x 40 mg daily, n = 65 (2) Placebo plaster, n = 66	(1) 2/65 (2) 0/66	None	None	AE: 0 (1) 1/65 excluded from efficacy analysis for protocol violation (2) 2/66 (1 LoE, 1 cured)
Fioravanti 1999	(1) DHEP lecithin gel 3 x 5 g (= 65 mg) daily, n = 50 (2) DHEP gel 3 x 5 g (= 65 mg) daily, n = 50	(1) 0/50 (2) 1/50	No data	None reported	AE: none Other: none
Fujimaki 1985	(1) Piroxicam gel 0.5% 3 or 4 x 1 g daily, n = 92 (2) Indomethacin gel 1% 3 or 4 x 1 g daily, n = 90 (3) Placebo gel, n = 89	(1) 1/83 (2) 5/82 (3) 2/82	(1) 0/83 (2) 1/82 (nausea and vomiting) (3) 0/82	None	AE: (1) 0, (2) 4, (3) 0 Unknown reasons: (1) 2, (2) 1 Did not return after 1st visit/irregular visits: (1) 6, (2) 6, (3) 7
Gallacchi 1990	(1) Diclofenac hydroxyethylpyrrolidine gel 1%, 4 x 2 g daily, n = 25 (Flector gel) (2) Diclofenac sodium 1% 4 x 2 g daily, n = 25 (Voltaren Emugel)	No AEs	None	None	AE: none Other: none
González de Vega 2013	(1) Traumeel gel 3 x 2 g daily, n = 140 (2) Traumeel ointment, n = 143 (3) Diclofenac gel 1% 3 x 2 g daily, n = 137	No usable data Infrequent, mild to moderate	No usable data	None	AE: none Other: (1) 11/140 (2) 12/137
Governali 1995	(1) Ketoprofen gel 5% 3 x 2‐3 g daily, n = 15 (2) Ketoprofen cream 1%, 3 x 2‐3 g daily, n = 15	No side effects	None	None	AE: none Other: none
Gualdi 1987	(1) Flunaxaprofen gel 2 x 3‐5 cm daily, n = 30 (2) Ketoprofen gel 2 x 3‐5 cm daily, n = 30	(1) 1/30 (2) 3/30	No data	None reported	AE: none Other: none
Haig 1986	(1) Benzydamine cream 3%, 6 x daily, n = 21 (2) Placebo cream, n = 22	No AEs reported	None	None reported	AE: none reported Other: no data
Hoffmann 2012	(1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 121 (2) DHEP (Flector) plaster x 1 daily, n = 115 (3) Placebo plaster, n = 118	Most AEs were minor local reactions (e.g. pruritus and erythema) in area of plaster, of mild to moderate intensity and resolved without interrupting treatment	No treatment‐related systemic AEs recorded	(2) 1 participant had 3 SAEs, none judged related to study medication	AE: none Exclusions: (1) 5/121 (2) 10/115 (3) 7/118 Excluded from per protocol analysis due to poor compliance or personal decision
Hofman 2000	(1) Diclofenac sodium gel 1%, 4 x 2 cm daily, n = 69 (2) Lysine clonixinate gel 5%, 4 x 2 cm (22.5 mg) daily, n = 73	(1) 1/58 (2) 1/61	None	None	AE: none LoE: (1) 9, (2) 8
Hosie 1993	(1) Felbinac foam 3% 3 x 2 g daily + placebo tablets, 3 x 1 daily, n = 140 (127 analysed for efficacy) (2) Ibuprofen tablets 3 x 400 mg daily + placebo foam 3 x 2 g daily, n = 147 (134 analysed for efficacy)	(1) 1/127 (2) 3/134	GI events: (1) 14/127, (2) 11/134 For (1) more mild, none definitely drug related, for (2) definitely related to study drug	None	AE: none Exclusions: (1) 13, (2) 13 did not return for 7 day follow‐up
Jenoure 1997	(1) DHEP plaster (Tissugel), 2 x daily, n = 44 (2) Placebo plaster 2 x daily, n = 41	(1) 1/44 (2) 1/41	No data	None reported	AE: none reported Other: none reported
Joussellin 2003	(1) DHEP plaster (Flector Tissugel 1%), 1 x daily, n = 68 (2) Placebo plaster 1 x daily, n = 66	(1) 1/68 (pruritus) (2) 3/66 (pruritus 2, burning 1) All AEs mild or moderate	(1) 1/68 (allergic reaction) (2) 0/66	None reported	AE: (1) 0/66 (2) 1/66 Other: (1) 3/66 (2) 2/66
Julien 1989	(1) Ketoprofen gel 2.5% 2 x 5 cm (= 50 mg) daily, n = 30 (2) Placebo gel, n = 30	(1) 1/30 (2) 0/30	Not reported	None	AE: none Other: none
Klainguti 2010	(1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 62 (2) DHEP plaster (Flector) x 1 daily, n = 61 (3) Placebo, n = 59	(1) 0/62 (2) 0/61 (3) 1/59 All AEs mild in nature and resolved spontaneously	(1) 1/65 (facial infection) (2) 1/61 (abdominal pain) (3) 0/59	None	AE: none Other: (1) 3/65 (2) 1/61 (3) 3/59
Kockelbergh 1985a	(1) Ketoprofen gel 2.5% 2 x 5 cm (= 15 mg) daily, n = 38 (2) Placebo gel, n = 36	(1) 1/38 (2) 1/26	Not reported	None	AE: none Other: none
Kuehl 2011	(1) DETP 1.3% plaster 2 x daily, n = 207 (2) Placebo plaster, n = 211	(1) 16/207 (2) 12/211	(1) 15/207 (2) 23/211	None	AE: (1) 4/207 (2) 9/211 LoE: (1) 21/207 (2) 25/211 Other: (1) 58/207 (2) 62/211
Li 2013	(1) DHEP plaster (Flector) 2 x daily, n = 192 (2) Placebo plaster 2 x daily, n = 192	(1) 4/192 (2) 3/192	(1) 10/192 (2) 4/192	None	AE: (1) 2/192 (2) 0/192 Other: (1) 5/192 (2) 1/192
Linde 1985	(1) Benzydamine 3% cream 3 x daily, n = 50 (2) Placebo gel, n = 50	(1) 4/40 (2) 2/41	None	None	AE: none (1) 6, (2) 6 excluded from 1st assessment (1) 3, (2) 4 excluded from final assessment
Machen 2002	(1) Ibuprofen gel 5% 3 x daily, n = 40 (2) Placebo gel, n = 41	(1) 4/40 (2) 2/41	None	None	AE: none (1) 1 LoE, 1 protocol violation (2) 4 LoE
Mahler 2003	(1) DHEP + lethicin gel 3 x 5 g daily, n = 52 (2) DHEP gel 3 x 5 g daily, n = 48	(1) 1/52 (2) 0/48	(1) 1/52 (2) 0/48	None	AE: none 5 lost to follow‐up
Mazières 2005b	(1) Ketoprofen plaster 100 mg, x 1 daily, n = 81 (2) Placebo plaster, n = 82	At 21 days: (1) 12/81 (2) 6/82	(1) 13/81 (2) 14/82	None	AE: (1) 3/81 (1) 7/81 (1 LoE, 6 cured) (2) 7/82 (5 LoE, 2 cured)
Mazières 2005a	(1) Ketoprofen plaster 100 mg, x 1 daily, n = 87 (2) Placebo plaster, n = 85	At 21 days: (1) 29/87 (2) 27/85	(1) 11/87 (2) 7/85	None	AE: (1) 9/87, (2) 6/85 (1) 6/87 (2 LoE, 4 cured) (2) 5/85 (4 LoE, 1 cured)
McLatchie 1989	(1) Felbinac gel 3% 3 x 3 cm daily, n = 118 (2) Placebo gel, n = 113	(1) 3/118 (2) 2/113 Mild transient local irritation	None reported	None	AE: none Other: none
Morris 1991	(1) Felbinac gel 3% 3 x 1 cm daily, n = 41 (2) Placebo gel, n = 43	None	None	None	AE: none (1) 4 (protocol violations) (2) 1 (lost to follow‐up) Exclusions: 11 from efficacy analysis because evaluated by 4 different investigators
NCT01255423	(1) Diclofenac sodium gel 1% x 4 daily, n = 104 (2) Placebo gel x 4 daily, n = 100	(1) 1/104 (2) 3/102	Total AE (1) 11/104 (2) 8/102	None	None
NCT01272934	(1) Diclofenac sodium gel 1% x 4 daily, n = 104 (2) Placebo gel x 4 daily, n = 100	(1) 1/102 (2) 0/103	Total AE (excluding SAE) (1) 6/102 (2) 3/103	(1) 0/102 (2) 1/103 (ruptured ligaments in wrist)	AE: see SAE
NCT01272947	(1) Diclofenac sodium gel 1% x 4 daily, n = 104 (2) Placebo gel x 4 daily, n = 100	None	(1) 2/104 (2) 2/100	None	None
Noret 1987	(1) Ketoprofen gel 2.5% 2 x 5 cm (7.5 mg) daily, n = 48 (2) Placebo gel, n = 45	(1) 1/51 (2) 0/47	None reported	Not reported	AE: (1) 1/51 (skin allergy) (1) 1 LoE, 1 unrelated to trial (2) 1 LoE, 1 unrelated to trial
Parrini 1992	(1) Ketoprofen foam 15% 3 x 2 g (200 mg) daily, n = 83 (2) Placebo foam, n = 86	None	None	None	AE: none Other: none
Picchio 1981	(1) Ibuprofen gel 10% 3 x daily , n = 20 (2) Ketoprofen gel 1% 3 x daily, n = 20	None	None	None	AE: none Other: not reported
Predel 2004	(1) Diclofenac sodium plaster, 2 x daily (140 mg/plaster), n = 60 (2) Placebo plaster, n = 60	12 participants experienced 16 mild AEs with no differences between groups	None	None	AE: (1) 1/60 Other: none
Predel 2012	(1) Diclofenac gel (Voltaren Emulgel 2.32%) 2 x 5 cm daily, n = 80 (2) Diclofenac gel (Voltaren Emulgel 2.32%) 3 x 5 cm daily, n = 80 (3) Placebo gel, n = 82	(1) 0/80 (2) 1/80 (3) 1/82 All mild to moderate	(1) 2/80 (2) 1/80 (3) 3/82	None	AE: (1) 0/80 (2) 0/80 (3) 1/82 Other: (1) 1/80 (2) 2/80 (3) 2/82 (protocol violations, lost to follow‐up)
Predel 2013a	(1) Diclofenac 4% spray gel 4 or 5 sprays 3 x daily (96‐120 mg diclofenac sodium), n = 118 (2) Placebo spray gel, n = 114	(1) 1/118 (2) 4/114	(1) 5/118 (2) 4/114 All AEs mild, reversible	None	AE: (1) 1/118 (2) 1/114 Other: (1) 3/118 (2) 43/114
Predel 2013b	(1) Diclofenac gel (Voltaren Emulgel) 4 x 2 g daily, n = 36 (2) Placebo gel 4 x 2 g daily, n = 36	None	(1) 0/36 (2) 1/36	None	AE: none Other: none
Ramesh 1983	(1) Ibuprofen cream 5% 3 or 4 x 5‐10 cm daily, n = 40 (2) Placebo cream, n = 40	(1) 1/40 (2) 1/40	None reported	Not reported	AE: (1) 1/40, (2) 1/40 Other: none
Rowbotham 2003	(1) DHEP plaster (Flector Tissuegel) 2 x daily, n = 191 (2) Placebo plaster, n = 181	(1) 27/191 (pruritis 14) (2) 31/181 (pruritis 21)	(1) 21/191 (2) 22/181	None reported ("vast majority mild")	AE: none (1) 3/191, (2) 4/181 (did not finish trial and complete daily diaries)
Russell 1991	(1) Piroxicam gel 0.5% 4 x 5 mg daily, n = 100 (2) Placebo gel, n = 100	(1) 4/102 (2) 10/102	GI or CNS events: (1) 4, (2) 7 Any AE: (1) 7/102, (2) 15/102	None reported	AE: (1) 1/102, (2) 8/102 Other: (1) 6 LoE, 1 "other" (2) 42 LoE Exclusions: 7 did not comply with study medication schedule, 6 lost to follow‐up, 1 protocol violation
Saillant 1998	(1) DHEP plaster (Flector Tissugel 1%) 1 x daily, n = 70 (2) Placebo plaster 1 x daily, n = 70	None	None	None	AE: none Other: (1) 5/70 (2) 5/70
Sanguinetti 1989	(1) Felbinac gel 3% 3 x daily, n = 42 (2) Placebo gel, n = 40	(1) 3/42 (2) 1/40	None	None reported	AE: none Other: none reported
Sinniger 1981	(1) Fentiazac cream 5% 2 or 3 x daily, n = 10 (2) Placebo cream, n = 10	"No untoward side effects"	None	None	AE: none Other: none reported
Spacca 2005	(1) DHEP lecithin gel (Effigel), 3 x 5 g, daily, n = 79 (2) Placebo gel, n = 76	"No signs of cutaneous irritation or sensitisation observed"	No AEs observed	None	AE: none Other: none reported
Sugioka 1984	(1) Piroxicam gel 0.5% 3 or 4 x 1 g daily, n = 183 (2) Indomethacin gel 1% 3 or 4 x 1 g daily, n = 183	(1) 5/178 (2) 26/179	None reported	None reported	AE: none reported Exclusions due to protocol violations: (1) 8, (2) 18 Withdrawals: (1) 11, (2) 12
Thorling 1990	(1) Naproxen gel 10% 2‐6 x daily, n = 60 (2) Placebo gel, n = 60	(1) 1/60 (2) 0/60	None	None	AE: none (1) 1 LoE, 1 protocol violation (2) 1 participant request
Tonutti 1994	(1) Ketoprofen gel 5%, 3 x 2‐3 g daily, n = 15 (2) Etofenamate gel 5%, 3 x 2‐3 g, n = 15	None	No AEs attributable to the medication	None	AE: None LoE: (1) 1, (2) 2
Vecchiet 1991	(1) Meclofenamic acid gel 5% 2 x 10 cm daily (2 g), n = 30 (2) Placebo, n = 30	Tolerability excellent or good in nearly all participants	No data	None	AE: none reported (2) 5 lost to follow‐up
Whitefield 2002	(1) Ibuprofen gel 5% + placebo tablet 3 x daily, n = 50 (2) Ibuprofen 400 mg tablet + placebo gel 3 x daily, n = 50	No data	6 AEs reported, none judged related to study medication	None reported	AE: none Recovered: (1) 3, (2) 2 LoE: (2) 1 Lost to follow‐up: (1) 1, (2) 1
AE: adverse event; CNS: central nervous system; DHEP: diclofenac epolamine; GI: gastrointestinal; HCl: hydrochloride; LoE: lack of efficacy; n: number; SAE: serious adverse event.