To evaluate the efficacy of tramadol as adjunctive therapy in patients with musculoskeletal pain attributed to osteoarthritis (OA) who experienced breakthrough pain while taking a nonsteroidal antiinflammatory drug (NSAID).This single center, parallel, placebo controlled, 2 phase study was conducted in adults who experienced breakthrough OA pain while undergoing stable NSAID therapy. In a 24 h open label phase, patients took 100 mg of tramadol followed by 50 mg every 6 h (total 250 mg) in addition to their daily NSAID regimen. Supplemental analgesics were prohibited. Patients who met entry criteria and were willing to continue therapy were randomized to a 13 day double blind phase of adjunctive therapy with tramadol (50-100 mg every 4-6 h as needed for pain) or placebo; NSAID therapy was continued. The primary efficacy endpoint was the time to exit from the study because of therapeutic failure (i.e., insufficient pain relief or an inability to perform activities of daily living).The time to exit from the study because of insufficient pain relief tended to be longer in the tramadol group (250 mg/day) compared with the placebo group (p = 0.066). At the end of the double blind phase, pain at rest was significantly less severe in tramadol treated patients (p = 0.046). In addition, severity of pain on motion tended to be less severe in tramadol treated patients (p = 0.059). General severity of current pain and ability to perform activities of daily living were not significantly different with tramadol or placebo. Patients' overall assessment of therapy (p = 0.022) and investigator's rating of global improvement (p = 0.004) were significantly better with tramadol than with placebo.Tramadol may have a role as adjunctive treatment for breakthrough pain in patients receiving NSAID therapy for musculoskeletal pain attributed to OA.
To compare efficacy and gastrointestinal (GI) tolerability of a new enteric coated formulation of naproxen (NAP-EC) with standard immediate release naproxen (NAP-STD).One hundred seventy-nine patients with osteoarthritis (OA) and one hundred seventy-six patients with rheumatoid arthritis (RA) at high risk for developing GI side effects to nonsteroidal antiinflammatory drug (NSAID) therapy were enrolled in a double blind, parallel, multicenter study. All patients had either discontinued as NSAID during the previous one year or required cotreatment with antiulcer drugs for control of GI complaints related to NSAID use. The treatments were evenly divided in both diagnostic cohorts.Except for minor differences in alcohol consumption, baseline characteristics of patients in both treatment groups were statistically similar. Both naproxen formulations were highly efficacious by all variables of disease activity when changes were measured from baseline. No statistically significant between formulation difference was found in the primary efficacy variable, overall disease activity. Overall, between formulation differences in efficacy measures were few, though most favored NAP-STD. GI complaints were reduced by 15% (51% NAP-EC vs 60% NAP-STD, p = 0.077) and GI complaints thought to be drug related were reduced by 36% (16% NAP-EC vs 25% NAP-STD, p = 0.024). Withdrawals due to GI complaints were reduced by 37% in the NAP-EC group (12% NAP-EC vs 19% NAP-STD, p = 0.054), and withdrawals due to GI complaints judged to be drug related were reduced by 55% in the NAP-EC group (6% NAP-EC vs 12% NAP-STD, p = 0.025).Enteric coated naproxen is an effective treatment for OA and RA. All observed differences in GI tolerability favor NAP-EC over NAP-STD.
Methods: Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo). Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO), and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs), recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation. Results: AEs occurred in 312 (67.1%) patients using TDiclo versus 298 (64.5%) of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001). Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001) and cardiovascular (1.5% vs 3.5%; P = 0.055) AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin ( P < 0.001 for all). Conclusions: These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile. Keywords: diclofenac, gastropathy, oral NSAIDs, osteoarthritis, topical NSAIDs
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may offer a safer alternative to their oral counterparts for the management of osteoarthritis. Diclofenac sodium topical solution with dimethyl sulfoxide (TDiclo) was evaluated in five randomized, controlled trials and is indicated for treatment of the signs and symptoms associated with osteoarthritis of the knee. Three studies showed that TDiclo is superior to placebo and vehicle control with respect to pain, physical function, and perception of osteoarthritis symptoms. Two studies showed that benefits are similar to those of oral diclofenac, with one study demonstrating statistical equivalence. The most common adverse event associated with TDiclo in these studies was dry skin. Incidences of gastrointestinal adverse events and abnormal levels of liver enzymes were lower with TDiclo compared with oral diclofenac in active-controlled studies. Based on these studies, TDiclo represents a practical, evidence-based option for the management of osteoarthritis of the knee.
Division of Anesthesiology, Cleveland Clinic Foundation, Cleveland, Ohio 44106 *Department of Anesthesia and Critical Care, The University of Chicago Medical Center, Chicago, lllinois 60637
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
