Study |
N |
Agent(s) |
Comparator |
Results |
Comments |
Strong Opioid/APAP Combinations |
Raffaeli 2010 [123] |
29 RA patients with chronic moderate to severe pain, not taking biologics |
Oxycodone/APAP started at 5/325 mg and titrated to attainment of good pain relief |
None |
42% had good clinical response (EULAR) and 50% showed 20% improvement. Mean daily dose at end of study was 13.8 (±6.8) mg/720.4 (±291.0) mg |
Mild to moderate nausea and vomiting; no serious AEs. Patients were allowed antiemetic drugs and laxatives as needed. |
Corsinovi 2009 [124] |
154 women nursing home residents with moderate to severe OA pain |
Oxycodone/APAP (average dose 16/900 mg) and codeine/APAP (average dose 115/1916 mg) |
Conventional therapy (NSAIDs, APAP, COX-2 inhibitors) |
Oxycodone/APAP and codeine/APAP significantly reduced mean pain at six weeks versus conventional therapy (p<0.001 and p=0.004, respectively) |
AEs did not differ significantly among groups.
Patients were all elderly females. |
Weak Opioid/APAP Combinations |
Mullican 2001 [125] |
462 patients with OA or LBP |
Tramadol/APAP (37.5/325 mg)
(average dose 131/1133 mg) |
Codeine/APAP (30/300 mg)
(average dose 105/1054 mg) |
Tramadol/APAP was as effective as codeine/APAP and better tolerated |
Codeine patients had significantly higher rates of somnolence and constipation, while tramadol patients had higher rate of headache (NS) |
Palangio 2000 [126] |
469 chronic pain patients (31% had arthritis, n=145) |
1 tablet of hydrocodone/ibuprofen 7.5/200 mg daily (HI-1) or 2 tablets of same (HI-2) |
Codeine/APAP 30/300 mg |
HI-2 offered significantly greater pain relief than HI-1 or comparator; no efficacy differences between HI-1 and comparator |
No significant difference in AEs by group (83% HI-2, 80% HI-1, and 81% Comparator) but significantly more HI-2 patients discontinued therapy due to adverse events compared to HI-1 (26% vs 15%, p=0.013) |
Conaghan 2011 [127] |
220 patients with hip and/or knee pain
≥60 years of age |
7-day buprenorphine patches (range 5-25 µg/h) + APAP 1000 mg qid |
Codeine/APAP range 16 mg/1000 mg qid to 60 mg/1000 mg qid |
Non-inferiority of patch+APAP to codeine/APAP combination regarding analgesic efficacy
Comparable incidence of AEs |
High withdrawal rates in both groups |
Emkey 2004 [128] |
306 OA patients taking a COX-2 inhibitor |
Tramadol/APAP (37.5/325 mg) as add-on
(average dose 154/1332 mg) |
Placebo as add-on |
Tramadol/APAP patients had significantly better scores on VAS, pain relief and function; 13% of tramadol and 4% of placebo patients discontinued because of AEs |
|
Park 2011 [129] |
97 knee OA patients in sub-study (part of larger study, n=112) |
Tramadol/APAP (37.5/325 mg) Mean dose 3.23 tablets/day |
NSAID |
No significant differences in analgesia or AEs |
|
Alwine 2000 [130] |
403 patients with OA or low back pain |
Tramadol/APAP (37.5 mg/325 mg) 1 to 3 tablets per day |
4-week active control, thereafter open label (24 m) |
Tramadol/APAP rated “excellent” or “very good” by 39% of patients and 40% of investigators, average daily dose was 157 mg/1363 mg. |
24% of patients discontinued due to AEs |
Rosenthal 2004 [131] |
Subset of 113 patients ≥ 65 years with painful OA flares (from larger study of 308 patients) on stable NSAID or COX-2 inhibitor therapy ≥ 3 months |
Tramadol/APAP (37.5/325 mg) as add on (mean daily dose 168/1.458 mg) |
Control continued NSAID or COX-2 inhibitor therapy |
Tramadol/APAP patients had significantly reduced daily pain intensity and significantly greater average daily pain relief |
23% of tramadol/APAP and 9% of control patients reported treatment-related AEs. Tramadol/APAP vs control rates of constipation and somnolence were 4.3% vs 2.3% and 2.9% vs 2.3%, respectively. |
Silverfield 2002 [132] |
308 OA patients with flare on stable NSAID or COX-2 inhibitor therapy |
Tramadol/APAP (37.5/325 mg) as add on |
Control continued NSAID or COX-2 inhibitor therapy |
Tramadol/APAP patients had significantly reduced daily pain intensity and significantly greater average daily pain relief |
AEs occurred in 24% of tramadol/APAP and 8% of control group; 13% of tramadol/APAP and 5% of control patients discontinued for AEs |
Lee 2006 [133] |
277 RA patients on stable NSAID and/or DMARD therapy for ≥ 1 month |
Tramadol/APAP (37.5/325 mg) as add on |
Control continued NSAID and/or DMARD therapy |
Tramadol/APAP patients had significantly greater pain relief and lower daily pain intensity |
AEs were 57.6% in tramadol/APAP group vs 22.4% in control (p<0.001) |
Choi 2007 [111] |
250 patients with pain from knee OA on stable NSAID therapy |
Tramadol/APAP (37.5/325 mg)
Mean daily dose 112.5/1.975 mg |
Patients were randomized to titration and non-titration groups |
Tramadol/APAP reduced pain in both titration and nontitration groups |
This was a safety study; discontinuation rate was significantly lower in titration group with nausea, vomiting and dizziness the most common AEs (all significantly more frequent in the nontitration group). |
NSAID/APAP Combinations |
Doherty 2011 [134] |
892 patients with chronic knee pain (85% had OA) |
Two active arms: 1 tablet or 2 tablets daily of ibuprofen/APAP 200/500 mg |
Two comparative arms: Ibuprofen 400 mg or paracetamol 1000 mg |
At day 10, 2 combination tablets were significantly better than APAP monotherapy; at 13 weeks, significantly more patients found combination therapy (1 or 2 tablets) excellent or good versus APAP monotherapy |
Decreases in hemoglobin (≥ 1 g/dl) occurred in all groups but was twice as frequent in patients taking 2 combination tablets daily compared to monotherapy |
Pareek 2010 [135] |
220 patients with knee OA flare |
Etodolac 300 mg/APAP 500 mg BID |
Etodolac 300 mg BID |
Etodolac/APAP significantly reduced pain intensity (p<0.001) and improved function |
Results noticeable within 30 minutes of first dose; AEs similar in both groups |
Pareek 2009 [136] |
199 patients with OA flares |
Aceclofenac 100 mg/APAP 500 mg BID |
Aceclofenac 100 mg BID |
Aceclofenac/APAP was superior to monotherapy in pain intensity differences, sum of pain intensity differences, and patients/ investigators assessments |
Combination had more rapid onset of action; AEs similar in both groups (about 10%) |