Summary of outcomes: successful treatment
Study ID	Treatment	Definition of clinical response Study duration	Number with successful outcome	Secondary measures
102‐93‐1	(1) Diclofenac solution (with 45.5% DMSO; Pennsaid®) (2) Control (with 45.5% DMSO) (3) Placebo (with 4.55% DMSO) Solution applied as 40 drops (about 1 mL) x 4 daily Number of participants in each group not reported	6 weeks	No dichotomous outcomes reported	Mean pain‐relief‐level days: (1) > (2) > (3)
108‐97	(1) Diclofenac solution (with 45.5% DMSO; Pennsaid®), n = 48 (2) Control (with 45.5% DMSO), n = 47 (3) Diclofenac solution (with 2.3% DMSO), n = 50 (4) Placebo (with 2.3% DMSO), n = 50 Solution applied 4 x daily to maximum 40 drops per hand	6 weeks	No dichotomous outcomes reported	(1) had greatest improvement in pain score, but differences between groups were not statistically significant
Altman 2009	(1) Diclofenac sodium gel 1% (Voltaren) with vehicle 2 g, n = 198 (2) Placebo gel (vehicle carrier) n = 187 Gels applied x 4 daily	OARSI response in dominant hand PGE 5‐point scale 8 weeks	OARSI responder: (1) 65.7% = 130/198 (2) 56.7% = 106/187	PGE: very good or excellent (1) 47.7% = 93/195 (2) 36.5% = 66/185
Baer 2005	(1) Diclofenac sodium 1.5% (with 45.5% DMSO; Pennsaid®), n = 107 (2) Placebo (vehicle carrier), n = 109 Solution applied as 40 drops x 4 daily	Participants with ≥ 50% PR (provided by author) PGE 5‐point scale 6 weeks	≥ 50% PR: (1) 46/105 (2) 27/107	PGE: good or very good (1) 46/105 (2) 18/107 OMERACT‐OARSI responder (post hoc) (1) 69/105 (2) 53/107 Significant improvement in score with topical diclofenac for pain, physical function, PGE, and stiffness at 6 weeks.
Balthazar‐Letawe 1987	(1) Diclofenac (Voltaren Emulgel), n = 25 (2) Indomethacin (Indocid) gel, n = 25 Gels applied x 2 daily	2 weeks	No dichotomous outcomes reported	No data
Baraf 2011	(1) Diclofenac sodium gel 1%, n = 721 (2) Placebo gel (vehicle only), n = 705 Medication applied 4 x 4 g daily	OARSI response in treated knee (using pain on movement) PGE 5‐point scale 12 weeks	OARSI: (1) 461/719 (2) 394/705	PGE: very good, excellent (1) 344/719 (2) 266/705
Bolten 1991	(1) Felbinac gel 3% 1 g, n = 142 (2) Placebo gel, n = 139 Gel applied x 3 daily	Pain on rest: 5‐point scale (‐1 to +3 where + = improvement) 2 weeks	Spontaneous pain (+3 or +2): (1) 34/142 (2) 15/139	Mean change in pain at rest or activity significantly improved after 14 days in (1)
Bookman 2004	(1) Diclofenac solution 1.5% in DMSO (45.5%: Pennsaid®), n = 84 (2) Carrier with DMSO (45.5%), n = 80 (3) Carrier with 1/10th DMSO (4.55%), n = 84 Solution applied as 40 drops (= 1.3 mL) x 4 daily	Participants with ≥ 50% PR (from author) 4 weeks	≥ 50% PR: (1) 44/84 (2) 26/79 (3) no data	Pain on walking at 4 weeks (4‐point scale): (1) 1.0 (SD 1.0) (2) 1.5 (SD 1.1) Mean change in pain, physical function, stiffness, pain on walking, and PGE score all statistically better for (1) than (2) or (3) Mean paracetamol consumption less in (1) than (2) or (3)
Bruhlmann 2003	(1) Diclofenac sodium patch 1% (180 mg; Flector‐EP), n = 51 (2) Placebo patch, n = 52 Patch applied x 2 daily	PGE 5‐point scale 2 weeks	PGE excellent: (1) 12/51 (2) 4/52	Number of patients judging the treatment group "no efficacy": (1) 5/51 (2) 9/52 Significantly greater reduction in mean spontaneous pain with (1) than (2) on day 7 and 14 There was a significant difference between treatment group and baseline at all 3 visits
Burgos 2001	(1) Flurbiprofen LAT (= 40 mg) + placebo cream, n = 64 (2) Piketoprofen cream 1.8% (4 cm ˜ 36 mg) + placebo patch, n = 65 Patch applied x 2 daily, cream x 3 daily	Undefined improvement: "Do you think that the treatment applied relieved the pain?" 2 weeks	Improved: (1) 80% = 46/58 (2) 65% = 39/60	Patients showed a significant mean improvement in all clinical parameters assessed: severity of disease, spontaneous pain, tenderness, and mobility of the involved joints, although no statistically significant differences between the 2 groups
Conaghan 2013	(1) Ketoprofen (IDEA‐033) gel 100 mg daily, n = 233 (2) Ketoprofen (IDEA‐033) gel 200 mg daily, n = 230 (3) 4.4 g vehicle daily, n = 238 (4) 8.8 g vehicle daily, n = 235 (5) Oral celecoxib 200 mg daily. N = 235 (6) Oral placebo, n = 228 All medication administered in divided daily dose (vehicle = TDT‐064)	Participants with ≥ 50% PR 12 weeks	≥ 50% PR: (1) 105/233 (2) 100/230 (3) 97/238 (4) 95/234 (5) 100/233 (6) 67/227	Mean PI reduction from baseline 1.9 (SD 1.6), ˜39%) in all groups except oral placebo (1.4 (SD 1.6), 29%) Mean change from baseline in physical function was similar for all treatment groups except oral placebo
Dickson 1991	(1) Piroxicam gel 0.5% (1 g = 5 mg piroxicam) + placebo tablet, n = 117 (2) Ibuprofen tablet 400 mg + placebo cream, n = 118 mg x 3 daily, n = 118  Gels applied x 3 daily, tablet taken x 3 daily	PGE 4‐point scale 4 weeks	PGE excellent or good: (1) 64% = 75/117 (2) 60% = 71/118	Mean reduction in pain and improvement in ability to perform task for all arthritic symptoms ‐ difference not significant between gel and oral groups
Dreiser 1993	(1) Diclofenac (DHEP) patch (= 180 mg), n = 78 (2) Placebo patch, n = 77 Patch applied x 2 daily	PGE 5‐point scale 4 weeks	PGE excellent or good: (1) 55/78 (2) 21/77	(1) significantly better than (2) for group mean spontaneous pain from 4th day on
Ergun 2007	(1) Nimesulide gel 1% (Sulidin) 0.4 mg/10 cm2, n = 51 (2) Placebo gel, n = 23 Gels applied x 3 daily	PGE 5‐point scale 4 weeks	PGE very effective or effective: (1) 23/49 (2) 2/21	(1) significantly better than (2) for mean change in overall WOMAC score over 30 days, but individual components did not reach statistical significance
Galeazzi 1993	(1) Diclofenac (DHEP) plaster (= 180 mg diclofenac derivative), n = 30 (2) Placebo plaster, n = 30 Plasters applied x 2 daily	No patient‐reported dichotomous outcomes 2 weeks	No data	(1) better than (2) for pain on pressure after 5 days
Grace 1999	(1) Diclofenac (with lecithin) gel 2% (2.5 g), n = 38 (2) Placebo gel, n = 36 Gels applied as one scoop 3 x daily	PGE 4‐point scale 2 weeks	PGE mild or none: (1) 12/38 (2) 9/36	Non‐significant difference between 2 trial groups at baseline and post treatment on aggregated WOMAC and pain subscale scores (pain, stiffness, physical function). (1) significantly better than (2) for improvement in WOMAC pain subscale
Gui 1982	(1) Ibuprofen cream, n = 20 (strength, dose, quantity not reported) (2) Placebo cream, n = 20 Creams applied x 2 daily	Undefined improvement in pain 3 weeks	With movement: (1) 14/18 (2) 7/19 With pressure: (1) 15/20 (2) 7/20	(1) significantly better than (2) for mean improvement in pain (spontaneous, movement, pressure) and functional incapacity
Hohmeister 1983	(1) Flufenamate 3% plus salicylate 2% gel (Mobilisin), n = 49 (quantity not reported) (2) Placebo gel, n = 51 Gels applied x 3 daily	PGE 3 weeks	PGE very good or good: (1) 44/49 (2) 4/51	—
Kneer 2013	(1) Ketoprofen (IDEA‐033) gel 50 mg daily, n = 223 (2) Ketoprofen (IDEA‐033) gel 100 mg daily, n = 223 (3) Ketoprofen (IDEA‐033) gel 200 mg daily, n = 221 (4) Vehicle, n = 199 All medication administered in divided daily dose	OMERACT/OARSI response 12 weeks	OMERACT/OARSI (ITT) (1) 88.6% = 190/214 (2) 86.8% = 185/213 (3) 88.6% = 187/211 (4) 77.5% = 147/190	PGE ‐ group mean data only. No clinically relevant differences at week 12 Mean PI reduction from baseline (1) 34/100 (2) 37/100 (3) 37/100 (4) 33/100
Link 1996	(1) Ketoprofen gel 2.5%, n = 56 (2) Placebo gel, n = 59 Gels applied as 4 to 10 cm strip x 3 or 4 daily	No patient‐reported dichotomous outcomes 2 weeks	No data	—
McCleane 2000	(1) Piroxicam gel 2.5%, n = 40 (2) GTN 1%, n = 36 (3) Piroxicam gel 2.5%/GTN 1%, n = 37 (4) Placebo gel, n = 46 Gels applied as "small volume" x 3 daily	Participants with ≥ 50% relief of pain  4 weeks	≥ 50% PR: (1) 1/40 (2) 4/36 (3) 7/37 (4) 4/46	Significant reduction in mean pain scores in group (4), with no fall in the placebo and piroxicam groups (this is probably relative to baseline as opposed to head‐to‐head comparison)
NCT01980940	(1) Etoricoxib gel 50 mg, 4% DMSO, n = 24 (2) Placebo gel, n = 24	PGE 5‐point scale 2 weeks	PGE of treatment, well or very well: (1) 13/24 (2) 14/24	No significant difference between groups for change in mean WOMAC pain score, function, or stiffness
Niethard 2005	(1) Diclofenac 1.16% gel (Voltaren Emulgel), n = 117 (2) Placebo gel, n = 121 Gels applied 4 g x 4 daily	PGE 5‐point scale 3 weeks	PGE excellent or very good: (1) 36/117 (2) 24/120	OMERACT‐OARSI responder at end of trial (1) 73/117 (2) 46/120
Ottillinger 2001	(1) Eltenac gel 1% 3 g, n = 57 (2) Eltenac gel 0.3% 3 g, n = 59 (3) Eltenac gel 0.1% 3 g, n = 59 (4) Placebo gel, n = 59 Gels applied as 4 inch string (approx 3 g) x 3 daily; to give 9 mg, 27 mg, 90 mg daily doses, or placebo	PGE (no details of scale) 4 weeks	No useable data	Patient‐reported global efficacy did not differ between treatments Measurement of global pain on VAS showed no significant difference for eltenac versus placebo
Poul 1993	(1) Flurbiprofen LAT patch, 40 mg, n = 53 (2) Placebo patch, n = 51 Medication applied as patch x 2 daily	Participants' overall efficacy estimates.  2 weeks	No useable data	There were statistically significant differences in favour of flurbiprofen LAT at both days 7 + 14 for the investigators' overall opinion of severity of condition Participant‐reported night pain, quality of sleep, day pain not significantly different between 2 treatment groups
Rose 1991	Piroxicam gel 5% (5 mg), n = 15 Placebo gel, n = 15 Gels applied 1 mg x 4 daily	PGE 4‐point scale 2 weeks	PGE excellent: (1) 8/15 (2) 8/15	—
Roth 1995	Diclofenac 3% + hyaluron 2.5% gel, n = 59 Placebo + hyaluron 2.5% gel, n = 60 Gels applied 2 g x 4 daily	Participant estimate of overall pain, 5‐point scale 2 weeks	No useable data	Analgesic effect of diclofenac gel was significantly greater than placebo at week 2
Roth 2004	(1) Diclofenac 1.5% with DMSO (45.5%; Pennsaid®), n = 164 (2) Carrier with DMSO (45.5%), n = 162 Solution applied as 40 drops x 4 daily	Participants with ≥ 50% PR (from author) 6 weeks	≥ 50% PR: (1) 79/163 (2) 55/159	Mean change in pain, physical function, stiffness and PGE all statistically better for (1) than (2) and also for pain on walking
Rother 2007	(1) Ketoprofen gel (IDEA‐33) 110 mg + placebo tabs, n = 138 (2) Celecoxib tabs 100 mg + placebo gel, n = 132 (3) Placebo gel and tabs, n = 127 Gel applied x 2 daily, tablet taken x 2 daily	PGE 5‐point scale 6 weeks	PGE excellent or good: (1) 64/138 (2) 51/132 (3) 35/127	Mean change in pain, but not physical function statistically better for (1) than (3) in ITT analysis. Both significantly better in PP analysis (2) better than (3) for both
Rother 2013	(1) Ketoprofen (IDEA‐033) gel 200 mg daily, n = 274 (2) 8.8 g vehicle daily, n = 281 All medication administered in divided daily dose	Participants with ≥ 50% PR 12 weeks	≥ 50% PR: (1) 41.2% = 113/274 (2) 50.5% = 142/281	PGE good or excellent at 12 weeks: (1) 54.7% = 150/274 (2) 60.5% = 170/281 Progressive improvements in mean PI (37% red) and function (about 40%) in both groups throughout study. Comparable between groups
Sandelin 1997	(1) Eltenac 1% gel + placebo tablets, n = 126 (2) Diclofenac tablet 50 mg + placebo gel, n = 82 (3) Placebo gel and tablets, n = 82 Gel applied as 3 g (= 30 mg eltenac or placebo) x 3 daily, tablets x 2 daily	No patient‐reported dichotomous outcome 4 weeks	No data	No significant difference in VAS score between the 3 groups
Simon 2009	(1) Diclofenac solution 1.5% (with DMSO 45.5%, Pennsaid®) + oral placebo, n = 154 (2) DMSO (45.5%) vehicle solution + oral placebo, n = 155 (3) Placebo solution (with 2.3% DMSO) + oral placebo, n = 161 (4) 100 mg slow‐release oral diclofenac + placebo solution (with 2.3% DMSO), n = 151 Solution applied as 40 drops of solution x 4 daily, tablet taken x 1 daily	Participants with ≥ 50% PR (from author) 12 weeks	50% PR: (1) 73/154 (2) 53/155 (4) 77/151	Topical diclofenac was statistically superior to placebo for all 3 primary variables (pain, physical function, patient overall health assessment); superiority was also observed for PGE but not stiffness A comparison of oral versus topical diclofenac found no statistically significant difference for any of the 5 efficacy variables above
Tugwell 2004	(1) Diclofenac solution (with 45.5% DMSO; Pennsaid®) placebo oral capsule, n = 311 (2) Diclofenac capsule + placebo topical solution (carrier with small quantity DMSO), n = 311 Solution applied as 50 drops of solution x 3 daily (daily total 4.6 mL = 75 mg diclofenac or placebo), oral capsule (50 mg diclofenac or placebo) taken x 3 daily	OMERACT‐OARSI responder 12 weeks	ITT analyses: (1) 201/303 (2) 210/301 PP analysis: (1) 167/236 (2) 184/254	Mean changes in pain, physical function, stiffness, and patient assessment not statistically different between groups
van Haselen 2000	(1) Piroxicam 0.5% gel, n = 91 (2) SRL gel: Symphytum officinale (comfrey), Rhus toxicodendron (poison ivy), and Ledum palustre (marsh‐tea), n = 89 Gels applied 1 g x 3 daily	PGE 6‐point scale 4 weeks	PGE excellent or good: (1) 20/91 (2) 38/89	Mean pain reduction as 8.1/100 mm (SD 25) in the piroxicam group and 16.5/100 mm (SD 24.6) VAS in the SRL group, an 8.4 mm difference between treatment groups (95% CI 0.8 to 15.9)
Varadi 2013	(1) VALE‐ibuprofen cream 4 g daily, n = 39 (2) Placebo cream, n = 36 All medication administered in divided daily dose	No dichotomous data 2 weeks	No dichotomous data	Mean decrease in PI on walking from baseline to week 2: (1) 2.0/10 (SD 2.4) (2) 1.6/10 (SD 1.9) Mean improvement in function greater with ibuprofen than placebo (32% versus 16%)
Widrig 2007	(1) Ibuprofen 5% gel (Optifen), n = 98 (2) Arnica 50% gel, n = 100 Gel applied as 4 cm strip x 3 daily	PGE 4‐point scale 3 weeks	PGE very good or good: (1) 56.5% = 50/85 (2) 64% = 57/89	Mean change in pain and hand function not significantly different between groups
Zacher 2001	(1) Diclofenac Emulgel (verum) + placebo tabs, n = 165 (2) Oral ibuprofen 300 mg + placebo gel, n = 156 Gel applied x 4 daily, tabs taken x 3 daily	≥ 40% PR (unclear if physician or patient assessment reported) 3 weeks	≥ 40% PR modified ITT: (1) 66/165 (2) 53/156	—
DMSO: dimethyl sulphoxide; ITT: intention‐to‐treat; n: number of participants in the treatment arm; OARSI: Osteoarthritis Research Society International; OMERACT: Outcomes Measures in Rheumatology Clinical Trials; PGE: patient global evaluation; PR: pain relief; SD: standard deviation; VAS: visual analogue scale; WOMAC: Western Ontario and McMaster Universities Arthritis Index