Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis

OBJECTIVE: To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS: Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy. CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).     

Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. conventional therapy in elderly women with persistent, moderate to severe osteoarthritis-related pain

We aimed to evaluate the efficacy and safety of oxycodone/acetaminophen (O/A) and codeine/acetaminophen (C/A) vs. conventional therapy (CT) without opioids in older women suffering from osteoarthritis (OA)-related pain, sub-optimally responsive to prior conventional treatments. We performed a 6 week, randomized, single blind, controlled study in three nursing homes. We enrolled 154 women with painful OA. They were assigned to treatment with O/A (n = 52) and C/A (n = 52) vs. CT (n = 50). We evaluated at baseline and at week 6: average pain in the last week (mean pain, MeP), pain at rest (RP), pain in movement (MP) (numeric rating scale, NRS); depressive symptoms (Beck Depression Inventory-II, BDI-II); functional status (activities of daily living, ADL) and cognitive status (mini mental state evaluation, MMSE). We considered the adverse events (AEs) in the study period. At week 6, MeP, RP and MP were significantly reduced in all three groups (p < 0.001); compared to CT, O/A and C/A were associated with greater reductions in MeP (p < 0.001 and p = 0.004, respectively), in RP (p = 0.028 and p = 0.032, respectively) in MP (p < 0.001 and p = 0.002, respectively) and with significant improvement in BDI-II score (p = 0.05 and p = 0.04, respectively) and ADL value (p = 0.04 and p = 0.05, respectively). AE rates did not differ between groups.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial

OBJECTIVE: Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study. METHODS: The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group. CONCLUSION: TDF can reduce pain and improve function in patients with knee or hip OA.     

Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen

OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with moderate-to-severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic. METHODS: Data were obtained from a randomized, double-blind study of patients with moderate-to-severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF-36 scores were compared across the tertiles. Mean changes in SF-36 and FIQ scores were compared between treatment groups. RESULTS: Patients with fibromyalgia scored lower than the US norm on all SF-36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF-36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01). CONCLUSION: Moderate-to-severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized,placebo‐controlled trial

Objective

Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.

Methods

The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.

Conclusion

TDF can reduce pain and improve function in patients with knee or hip OA.

     

Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls

BACKGROUND AND AIMS: Health-related quality of life (HRQOL) assessment is receiving increasing attention as an outcome measure in osteoarthritis (OA). The aims of this study were to compare HRQOL among older adults aged 55 to 78 years with hip and/or knee OA with those without OA, and to assess the influence of selected variables (sex, body mass index, radiographic OA severity, educational level, comorbidities) on HRQOL. METHODS: The generic Medical Outcome Study Short Form-36 item health status questionnaire (SF-36) was administered to a cohort of 264 OA patients (105 with hip OA alone, 108 with knee OA alone, and 51 with both hip and knee OA) and 112 healthy controls. RESULTS: Compared with the healthy controls, OA of the lower extremities has a detrimental effect on the eight-scale profile score, as well as on physical and mental summary measures of the SF-36. The most striking impact was seen in the physical measures "physical functioning", "physical role" and "pain" (p<0.0001). No statistically significant differences in SF-36 scores were found among the three groups of OA patients. The physical and mental summary scales of the SF-36 were closely correlated (p<0.0001). One hundred and forty-five patients (54.9%) reported at least one chronic coexisting disease. There was a significant inverse association with measures of comorbidity (number of comorbidities and comorbidity index score) and both physical and mental summary scores of the SF-36 questionnaire. In patients with OA of the knee alone (but not in hip OA alone or hip and knee OA), the SF-36 pain score was inversely correlated with years of formal education (p=0.016). In addition, the impact of hip and knee SF-36 dimensions was not influenced by the degree of radiographic severity. CONCLUSIONS: Older adults with OA of the lower extremities undergo a significant impact on multiple dimensions of HRQOL, compared with healthy controls. The use of a generic measure of HRQOL such as the SF-36, in studies of OA where comorbidity is common, should be useful in characterizing the global burden of this disease.     

Hydrocodone versus codeine in acute musculoskeletal pain

STUDY OBJECTIVES: To evaluate the efficacy and prevalence of side effects of hydrocodone versus codeine in acute pain syndromes. TYPE OF PARTICIPANTS/SETTING: Sixty-two consecutive adult emergency department patients 18 to 70 years old with acute musculoskeletal pain. Patients using other analgesics or having any contraindication to opioid therapy were excluded. In addition, 12 patients were excluded because of insufficient data or study dropout. DESIGN/INTERVENTIONS: In a randomized, double-blind prospective manner, patients received either 5 mg hydrocodone with 500 mg acetaminophen or 30 mg codeine with 500 mg acetaminophen to take on discharge from the ED and every four hours thereafter as needed for pain. MEASUREMENTS: Pain intensity was evaluated by a visual analog scale at zero, one, two, four, eight, 24, and 48 hours. Specific side effects were sought, along with the number of patients reporting inadequate analgesia. MAIN RESULTS: Data were obtained on 50 subjects (25 per group). Mean and median pain scores did not differ significantly at time zero (x vs y, 6.03 vs 5.99 and 6.8 vs 6.1, respectively) or subsequent intervals. Side effects were noted in eight hydrocodone/acetaminophen and 18 codeine/acetaminophen patients (P = .005). No significant differences in gastrointestinal side effects were reported; however, less nausea or vomiting was reported in the hydrocodone group (P = .23). Central nervous system side effects (sedation or lightheadedness) were reported in six hydrocodone/acetaminophen patients compared with 16 codeine/acetaminophen patients (P less than .005). In addition, no hydrocodone/acetaminophen patients reported inadequate analgesia compared with six codeine/acetaminophen patients (P less than .05). CONCLUSION: Although pain scores were not significantly different, hydrocodone may be a more effective analgesic than codeine in acute musculoskeletal pain, as demonstrated by significantly fewer treatment failures. Central nervous system side effects are less common with hydrocodone than with codeine.     

Health-related quality of life (HRQOL) in older people practicing Tai Chi--comparison of the HRQOL with the national standards for age-matched controls

AIM: We assessed health-related quality of life (HRQOL) of community-dwelling older people who practiced Tai Chi in a cross-sectional study using the MOS 36-item short-form health survey (SF-36, Japanese version). METHODS: SF-36 and another questionnaire about age, sex, experience with Tai Chi, were distributed to 903 people who were above 65 years old and belonged to the Japan Health Tai Chi Association. Of these, 804 people responded (89.04%). From the SF-36, we used the sub-scores for physical functioning (PF), physical role (PR), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). These sub-scores were compared with those obtained from age-matched national standards for groups 60 to 69 years old and 70 to 80 years old respectively (n=1.040). RESULTS: The 60- to 69-year-old subjects had significantly higher PF (p<0.01), GH (p<0.05), and MH (p<0.01) than the national averages. For the 70- to 80-year old subjects, PF (p<0.01), PR (p<0.01), BP (p<0.05), GH (p<0.01), VT (p<0.01), RE (p<0.01), and MH (p<0.01) were significantly higher than the national averages. The number of years and the frequency of practicing Tai Chi statistically significantly correlated with MH and PF, and GH and PF, respectively. CONCLUSION: The HRQOL of the people who practiced Tai Chi was better than age-matched national standards. Although the number of years and the frequency of practicing Tai chi statistically significantly correlated with the sub-scores of the HRQOL, the adjusted (R(2)) were low.     

Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee

OBJECTIVE: Pain is the cardinal feature of osteoarthritis (OA), and with advancing disease there is loss of function and increasing pain even at times of joint rest. Few studies have evaluated the role of opioid analgesics in treating the pain of OA. METHODS: This randomized, double blind, parallel group study compared the efficacy and safety of a 12 hourly controlled release codeine formulation (Codeine Contin) with placebo in patients with chronic pain due to OA of the hips and/or knees. The 4 week treatment period, following an analgesic washout phase of 2-7 days, included weekly clinic evaluations, at which the dose was escalated as appropriate, and daily patient diary completion. Pain (daily), stiffness, and physical function (weekly) were assessed using the multidimensional, self-administered WOMAC (visual analog scale version) questionnaire. RESULTS: Sixty-six eligible patients completed the study. The mean initial and final daily doses of controlled release codeine were 50 mg every 12 h at baseline and 159 mg every 12 h at the final assessment. All variables in the efficacy analysis indicated superiority of controlled release codeine over placebo. The WOMAC pain scale showed an improvement of 44.8% over baseline in the controlled release codeine group compared with 12.3% taking placebo (p = 0.0004). For the WOMAC stiffness and physical function scales the improvements over baseline on controlled release codeine were 47.7% and 49.3%, respectively compared with 17.0% and 17.0%, respectively, with placebo (p = 0.003; p = 0.0007). Controlled release codeine was also significantly better than placebo on measures of sleep quality and requirement for supplemental acetaminophen. CONCLUSION: Single entity controlled release codeine is an effective treatment for pain due to OA of the hip or knee.     

Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib

OBJECTIVES: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis OA in a 13 week, multicentre, randomised, double blind study. METHODS: After a 37 day washout period for nonsteroidal antiinflammatory drugs, 1702 patients with knee OA were randomised to lumiracoxib 200 or 400 mg once daily od, celecoxib 200 mg od, or placebo 2221. A visual analogue scale VAS pain intensity > or =40 mm was required. Primary efficacy variables were OA pain intensity VAS mm in the target knee, patients global assessment of disease activity VAS mm, and WOMAC pain subscale and total scores at 13 weeks. OA pain intensity, patients and physicians global assessment of disease activity, and WOMAC total and all subscale scores were analysed by visit as secondary variables. RESULTS: Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo. Lumiracoxib 200 mg od and celecoxib 200 mg od achieved similar improvements in OA pain intensity and functional status. Lumiracoxib 400 mg od demonstrated better efficacy for OA pain intensity and patients global assessment of disease activity at weeks 2, 4, and 8 and similar efficacy at week 13 compared with celecoxib 200 mg od. The incidence of adverse events AEs, serious AEs, and discontinuations due to AEs was similar in each group. CONCLUSION: Lumiracoxib demonstrated significant improvement in OA pain intensity, patients global assessment of disease activity, and the WOMAC pain subscale and total scores compared with placebo. Lumiracoxib was well tolerated in this study, with overall tolerability similar to that of placebo and celecoxib.     

Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: Results from a phase III,randomized, active-controlled,adequate, and well-controlled trial

Objectives: S-flurbiprofen plaster (SFPP) is a novel non-steroidal anti-inflammatory drug (NSAID) patch, intended for topical treatment for musculoskeletal diseases. This trial was conducted to examine the effectiveness of SFPP using active comparator, flurbiprofen (FP) patch, on knee osteoarthritis (OA) symptoms.

Methods: This was a phase III, multi-center, randomized, adequate, and well-controlled trial, both investigators and patients were blinded to the assigned treatment. Enrolled 633 knee OA patients were treated with either SFPP or FP patch for two weeks. The primary endpoint was improvement in knee pain on rising from the chair as assessed by visual analogue scale (rVAS). Safety was evaluated through adverse events (AEs).

Results: The change in rVAS was 40.9?mm in SFPP group and 30.6?mm in FP patch group (p?p?Conclusions: The superiority of SFPP in efficacy was demonstrated. Most of AEs were mild and few AEs led to treatment discontinuation. Therefore, SFPP provides an additional option for knee OA therapy.     

The use of opioids in the treatment of osteoarthritis: When, why, and how?

As life expectancy increases every decade, the incidence and prevalence of osteoarthritis (OA) also will increase. Despite progress in our knowledge of the pathophysiology of OA, the management of OA-mediated pain continues to challenge physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2 inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in general has limited the use of these medications in the management of chronic non-cancer pain. Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care. When used as part of a multimodal approach to pain control, opioids are a safe and effective treatment for joint pain, including that of OA. Patients for whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol, and NSAID therapy is ineffective, may be started on low-dose opioids and titrated as needed and tolerated. Patient education and informed consent, exercise, complementary medicine, and the use of a controlled substance agreement increases the likelihood of patient compliance with treatment guidelines, improving functional capacity and quality of life.     

Quality of life and functional capacity are adversely affected in osteoarthritis patients with neuropathic pain

The aim of this study was to examine the neuropathic pain component of knee osteoarthritis (OA) patients and to investigate the relationship between neuropathic pain, disease stage, functional state, depression, anxiety, and quality of life. This study included 60 patients with knee OA. All demographic data and radiological results were recorded. Visual Analog Scale (VAS), Timed Up and Go Test, Chair Stand Test, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), PainDETECT questionnaire, DN4 questionnaire, Short form-36 questionnaire, and Hospital Anxiety Depression Scale were performed for each patient. Neuropathic pain was detected in 66.7% of patients based on the PainDETECT scale and in 46.7% of patients based on DN4 scale. VAS-resting, OA grade, WOMAC scores, and SF-scores showed a significant difference in patients that detected neuropathic pain with PainDETECT (p < 0.05). Based on the DN4 scale, patients with neuropathic pain had significantly higher WOMAC scores and significantly lower SF-36 scores (p < 0.05). The PainDETECT questionnaire scores showed positive correlations with Timed Up-and-go Test, VAS-resting, WOMAC scores, Hospital Anxiety Depression Scale scores, and a negative correlation with all SF-36 scores (p < 0.05). DN4 questionnaire scores showed a negative correlation with SF-36 scores and positive correlation with WOMAC scores (p < 0.05). To conclude, it should be kept in mind that patients with knee OA who describe intense pain may have a neuropathic component involved in the clinical condition. Quality of life and functional capacity are adversely affected in patients with knee OA who have neuropathic pain. This should be taken into account while planning the treatment of these patients.     

A naturalistic study of the determinants of health related quality of life improvement in osteoarthritic patients treated with non-specific non-steroidal anti-inflammatory drugs

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes. METHODS: A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up. RESULTS: All QoL dimensions were significantly (p<0.01) decreased in patients with OA compared with controls. Significant improvement (p<0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA. CONCLUSION: OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs.     

Quality of life and self-reported disability in patients with knee osteoarthritis

Abstract

Objectives Osteoarthritis (OA) is the most common degenerative joint disorder and a major public health problem throughout the world. The aims of this study are to assess quality of life (QoL) in patients with knee OA using the generic instrument Short Form-36 (SF-36) and to determine its relationships with conventional clinical measures and self-reported disability.

Methods Patients with knee OA (n = 112) with median age of 60 (45–76) years and 40 sex- and age-matched healthy controls were included in the study. Age, sex, body mass index (BMI), symptom duration, and Kellgren–Lawrence scores were recorded. QoL, disability, and pain were assessed using the SF-36, the Western Ontario and McMaster (WOMAC) index, the Lequesne index, and a visual analog scale (VAS) in patients. Also, QoL was assessed using the SF-36 in controls.

Results Patients with knee OA had lower scores in all subgroups of SF-36 compared with controls. In patients, the SF-36 physical function (PF) and pain areas significantly correlated with effusion, VAS pain, and Lequesne and WOMAC subgroup scores (p < 0.05). The pain area of QoL did not show correlation with comorbidity with knee OA. We found that SF-36 and WOMAC pain scores were more severe in female patients.

Conclusions Patients with knee OA had significantly poorer QoL compared with healthy controls. SF-36 is related to the clinical status and functional ability of patients with OA and can be used as a sensitive health status measure for clinical evaluation. Also WOMAC can be used as a sensitive measure for disability of patients with knee OA.     

Severity of knee pain does not predict a better response to an antiinflammatory dose of ibuprofen than to analgesic therapy in patients with osteoarthritis

OBJECTIVE: To determine whether greater pain intensity at initiation of treatment predicted better response to ibuprofen than to acetaminophen in subjects with knee osteoarthritis (OA). METHODS: Data from 182 patients with knee OA who had taken part in a 4 week randomized, double blind, parallel comparison of 4,000 mg/day acetaminophen vs either 1,200 or 2,400 mg/day ibuprofen were reanalyzed using Pearson correlation coefficients for baseline pain severity, treatment assignment, and treatment response. Pain measures were visual analog scales for overall pain, resting pain, and walking pain. Baseline pain severity was divided into low, medium, and high tertiles, and treatment related differences in pain response were sought with pairwise t tests. Two-factor analysis of variance (ANOVA) models were used to seek interactions between baseline pain severity and treatment group, which would indicate differential drug treatment responsiveness. RESULTS: Greater baseline pain predicted greater pain relief with all 3 treatments. Patients with a high level of baseline rest pain appeared to respond better to ibuprofen 2,400 mg/day than to the other treatments, but this difference was not evident after correction for multiple statistical tests. ANOVA did not reveal significant differences in response to the 3 treatments or a significant interaction. CONCLUSION: Our data suggest that acetaminophen and ibuprofen are comparably effective in treating knee OA pain, even when the pain is severe.     

High anti-TNF alfa drugs trough levels are not associated with the occurrence of adverse events in patients with inflammatory bowel disease

Abstract

Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.

Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.

Results: During a median follow-up of 16?months (range 1–144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p?=?.21) in median TLs between patients who did 6.7?mcg/mL; range 0.0–36.2) or did not (7.7?mcg/mL; range 0.0–20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p?=?.38), as well as between elderly (i.e., >65?years) and younger patients (p?=?.32). Considering a TL cutoff of 7?mcg/mL for infliximab and 12?mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.

Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.     

Efficacy of lumiracoxib in relieving pain associated with knee osteoarthritis: a 6‐week,randomized, double‐blind,parallel‐group study

Aim: The aim of the current study was to assess the efficacy, safety, and tolerability of lumiracoxib 200 mg once daily (o.d.) in relieving osteoarthritis (OA) knee pain in patients in China, Taiwan, and South Korea. Methods: Patients of either sex (aged ≥ 18 years) with symptomatic, primary OA of the knee for ≥ 3 months were eligible for inclusion if they had OA pain intensity of ≥ 40 mm (100 mm visual analogue scale [VAS]) in the target knee joint during the previous 24 h. Patients were required to undergo regular non‐steroidal anti‐inflammatory drug therapy for ≥ 6 weeks. After 3–7 days of screening, patients were randomized (1 : 1) to receive either lumiracoxib 200 mg o.d. or celecoxib 200 mg o.d. The primary efficacy comparison between the study groups was overall OA pain intensity (VAS) in the target knee after 6 weeks of treatment. Results: The mean overall OA pain intensity (VAS) in the target knee after 6 weeks decreased from 60.6 mm to 35.7 mm and 60.5 mm to 36.1 mm in the lumiracoxib and celecoxib groups, respectively. Both study groups showed similar results in terms of improvement in both patient's and physician's global assessment of disease activity and functional health status. The percentage of adverse events (AEs) in the lumiracoxib and celecoxib groups (40.3% and 37.9%, respectively) was similar, as was the proportion of treatment‐related AEs (21.0% and 18.2%, respectively). Conclusions: Lumiracoxib 200 mg o.d. provided effective and well‐tolerated pain relief similar to that achieved with celecoxib 200 mg o.d. in knee OA patients.     

Steroid injection for osteoarthritis of the hip: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebo-controlled trial. METHODS: Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle. RESULTS: The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF-36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups. CONCLUSION: This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.     

Health-related quality of life in women with symptomatic hand osteoarthritis: a comparison with rheumatoid arthritis patients, healthy controls, and normative data

OBJECTIVE: Data on the burden of disease and impact on health-related quality of life (HRQOL) in hand osteoarthritis (OA) are limited. The goal of this study was to compare HRQOL in patients with hand OA with HRQOL in patients with rheumatoid arthritis (RA), healthy controls, and normative data from the general population. METHODS: A total of 190 women with hand OA were compared with 194 women with RA and 144 healthy women of the same age. Health status was measured using the Short Form 36 (SF-36), Short Form 6D (SF-6D), modified Health Assessment Questionnaire (M-HAQ), pain and fatigue visual analog scales, and grip strength. Scores were compared by analysis of variance and a multivariate analysis of covariance, adjusting for age, number of comorbidities, and years of education. Gaps between patients and population subjects were assessed by calculating S scores on all dimensions of the SF-36. RESULTS: Hand OA and RA patients had worse scores on all assessed dimensions of subjective health compared with healthy controls. RA patients showed poorest general health (SF-36), poorest physical function (M-HAQ, SF-36 physical, grip strength), and highest level of fatigue compared with hand OA patients. Hand OA patients reported poorer mental health. Mean utility scores (SF-6D) in hand OA and RA were 0.64 and 0.63, respectively, with a mean difference compared with healthy controls of 0.13 in hand OA and 0.14 in RA patients. S scores confirmed a marked disparity between individuals with a rheumatic diagnosis (hand OA, RA) and population subjects. CONCLUSION: This study illustrates that patients with hand OA experience a broad impact on HRQOL compared with healthy controls. Fatigue and physical function are worse in RA than hand OA.