The effectiveness of pulsed electrical stimulation in the management of osteoarthritis of the knee: Results of a double‐blind,randomized, placebo‐controlled,repeated‐measures trial

Objective

To determine the effectiveness of subsensory, pulsed electrical stimulation (PES) in the symptomatic management of osteoarthritis (OA) of the knee.

Methods

This was a double‐blind, randomized, placebo‐controlled, repeated‐measures trial in 70 participants with clinical and radiographically diagnosed OA of the knee who were randomized to either PES or placebo. The primary outcome was change in pain score over 26 weeks measured on a 100‐mm visual analog scale (VAS). Other measures included pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), function on the WOMAC, patient's global assessment of disease activity (on a 100‐mm VAS), joint stiffness on the WOMAC, quality of life on the Medical Outcomes Study Short‐Form 36 (SF‐36) health survey, physical activity (using the Human Activity Profile and an accelerometer), and global perceived effect (on an 11‐point scale).

Results

Thirty‐four participants were randomized to PES and 36 to placebo. Intent‐to‐treat analysis showed a statistically significant improvement in VAS pain score over 26 weeks in both groups, but no difference between groups (mean change difference 0.9 mm [95% confidence interval −11.7, 13.4]). Similarly, there were no differences between groups for changes in WOMAC pain, function, and stiffness scores (−5.6 [95% confidence interval −14.9, 3.6], −1.9 [95% confidence interval −9.7, 5.9], and 3.7 [95% confidence interval −6.0, 13.5], respectively), SF‐36 physical and mental component summary scores (1.7 [95% confidence interval −1.5, 4.8] and 1.2 [95% confidence interval −2.9, 5.4], respectively), patient's global assessment of disease activity (−2.8 [95% confidence interval −13.9, 8.4]), or activity measures. Fifty‐six percent of the PES‐treated group achieved a clinically relevant 20‐mm improvement in VAS pain score at 26 weeks compared with 44% of controls (12% [95% confidence interval −11%, 33%]).

Conclusion

In this sample of subjects with mild‐to‐moderate symptoms and moderate‐to‐severe radiographic OA of the knee, 26 weeks of PES was no more effective than placebo.

     

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: A phase II,four‐week,multicenter, randomized,double‐blind,placebo‐controlled trial

Objective

To compare the efficacy and tolerability of the novel cyclooxygenase 2‐selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA).

Methods

Adults (n = 583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting.

Results

All lumiracoxib doses were superior to placebo in relieving pain, improving stiffness, and improving physical function after 4 weeks. At study endpoint, pain relief was comparable among all lumiracoxib dosages and similar to diclofenac. Lumiracoxib tolerability was superior to diclofenac and comparable to placebo.

Conclusion

Lumiracoxib provides predictable and sustained relief from pain, stiffness, and impaired physical function in OA. Lumiracoxib shows clinically comparable efficacy and superior tolerability to diclofenac.

     

Increase in vastus medialis cross‐sectional area is associated with reduced pain,cartilage loss,and joint replacement risk in knee osteoarthritis

Objective

Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross‐sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA).

Methods

One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs).

Results

After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = −0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient −10.9 [95% CI −19.5, −2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient −16.8 [95% CI −28.9, −4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]).

Conclusion

In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

     

Effects of doxycycline on progression of osteoarthritis: Results of a randomized,placebo‐controlled,double‐blind trial

Objective

To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.

Methods

In this placebo‐controlled trial, obese women (n = 431) ages 45–64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6‐month intervals.

Results

Seventy‐one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ± SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ± 0.42 mm versus 0.24 ± 0.54 mm); after 30 months, it was 33% less (0.30 ± 0.60 mm versus 0.45 ± 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a ≥20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a ≥20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.

Conclusion

Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

     

Long‐term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention,a two‐year,randomized, double‐blind,placebo‐controlled trial

Objective

To assess the long‐term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA).

Methods

We performed an international, randomized, double‐blind, placebo‐controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years.

Results

The intent‐to‐treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean ± SEM −0.07 ± 0.03 mm) as compared with the placebo group (−0.31 ± 0.04 mm). The percentage of patients with radiographic progression ≥0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16–46%]). The number of patients needed to treat was 8 (95% confidence interval 5–17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups.

Conclusion

The long‐term combined structure‐modifying and symptom‐modifying effects of CS suggest that it could be a disease‐modifying agent in patients with knee OA.

     

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.

     

A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.

Results

The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T² test (P = 0.0115).

Conclusion

Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

     

Randomized,double‐blind,placebo‐controlled glucosamine discontinuation trial in knee osteoarthritis

Objective

To assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA).

Methods

A 4‐center, 6‐month, randomized, double‐blind, placebo‐controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine. Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day). Followup continued for 6 months or until disease flare, whichever occurred first. The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent‐to‐treat analysis. Secondary outcomes included time to disease flare; analgesic medication use; severity of disease flare; and change in pain, stiffness, function and quality of life in the glucosamine and placebo groups.

Results

Disease flare was seen in 28 (42%) of 66 placebo patients and 32 (45%) of 71 glucosamine patients (difference ?3%; 95% confidence interval [95% CI] ?19, 14; P = 0.76). In the Cox regression analysis, after adjustment for sex, study site, and OA radiographic severity, time to disease flare was not significantly different in the glucosamine compared with placebo group (hazard ratio of flare = 0.8; 95% CI 0.5, 1.4; P = 0.45). At final study visit, acetaminophen was used in 27% and 21% of placebo and glucosamine patients, respectively (P = 0.40), nonsteroidal antiinflammatory drugs were used in 29% and 30% (P = 0.92), and both were used in 20% and 21% (P = 0.84). No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients.

Conclusion

In patients with knee OA with at least moderate subjective improvement with prior glucosamine use, this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate.

     

Tidal irrigation as treatment for knee osteoarthritis: A sham‐controlled,randomized, double‐blinded evaluation

Objective

To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well‐matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA).

Methods

One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed.

Results

Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of SI and TI. Blinding was successful, with ∼90% of SI and TI subjects stating that they had received the TI procedure.

Conclusion

Most, if not all, of the effect of TI appears to be attributable to a “placebo response.”

     

Pilot study of the effects of a heat‐retaining knee sleeve on joint pain,stiffness, and function in patients with knee osteoarthritis

Objective

To identify changes in joint pain, stiffness, and functional ability in patients with knee osteoarthritis (OA) after use of a knee sleeve that prevents loss of body heat by the joint.

Methods

Subjects with symptomatic knee OA (n = 52) were randomized to 2 treatment groups: verum sleeve (specially fabricated to retain body heat) or placebo sleeve (standard cotton/elastane sleeve). Subjects wore the sleeve over the more painful OA knee for at least 12 hours daily for 4 weeks. Pain, stiffness, and functional impairment (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the index knee were measured at baseline and after 4 weeks of wear, after which sleeve use was discontinued. Telephone followup interviews were conducted 2 and 4 weeks later.

Results

After 4 weeks of sleeve wear, subjects in the active treatment group reported a 16% decrease in mean WOMAC pain score relative to baseline (P = 0.001). Those who wore the placebo sleeve reported a 9.7% decrease from baseline (P = 0.002). The difference between treatment groups was not statistically significant (P = 0.12). However, it was found that the 12 subjects who believed correctly that they had received the verum sleeve reported a highly significant decrease in WOMAC pain score (?27.5% relative to baseline, P = 0.0001). In comparison, subjects who received the verum sleeve but believed they had received the placebo sleeve exhibited only a marginally significant improvement in pain (?13.0% relative to baseline, P = 0.07). In the placebo group, the modest improvement in pain scores appeared unrelated to the subject's impression of the type of sleeve worn.

Conclusion

This pilot study was insufficiently powered to be a definitive trial of the heat‐retaining sleeve. Given the magnitude of changes in knee pain in the active treatment group, heat retention merits further scientific investigation as a treatment modality for patients with knee OA.

     

Comparing the efficacy of cyclooxygenase 2–specific inhibitors in treating osteoarthritis: Appropriate trial design considerations and results of a randomized,placebo‐controlled trial

Objective

To compare the efficacy of the cyclooxygenase 2 (COX‐2)–specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA).

Methods

In this randomized, placebo‐controlled, double‐blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).

Results

In primary measures of efficacy (OA pain score on a 100‐mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34‐mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was −2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events.

Conclusion

Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.

     

Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To evaluate the clinical response, safety, and tolerability of a single intraarticular injection of anakinra in patients with symptomatic osteoarthritis (OA) of the knee.

Methods

Patients with OA of the knee were enrolled in a multicenter, double‐blind, placebo‐controlled study and randomized 2:1:2 to receive a single intraarticular injection of placebo, anakinra 50 mg, or anakinra 150 mg in their symptomatic knee. Patients were evaluated for 12 weeks postinjection. The primary end point was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 4. Safety assessments included the evaluation of adverse events (AEs), laboratory tests, and vital signs. Pharmacokinetic parameters were assessed in a subset of patients.

Results

Of 170 patients who enrolled, 160 (94%) completed the study. The mean improvements from baseline to week 4 in the WOMAC score were not statistically different between the placebo group and the patients who received 50 mg of anakinra (P = 0.67) or 150 mg of anakinra (P = 0.77). Anakinra was well tolerated. No withdrawals due to AEs or serious AEs, and no serious infections or deaths were reported. No clinically significant trends were noted in laboratory values or vital signs. Pharmacokinetic parameters demonstrated that the mean terminal half‐life of anakinra in serum after intraarticular injection was ∼4 hours.

Conclusion

Anakinra was well tolerated as a single 50‐mg or 150‐mg intraarticular injection in patients with OA of the knee. However, anakinra was not associated with improvements in OA symptoms compared with placebo.

     

The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: A randomized,multicenter, double‐blind,placebo‐controlled study with primary end points at two months after the end of a three‐month treatment period

Objective

To determine whether the efficacy of diacerein persists at 2 months after the end of a 3‐month treatment period, compared with placebo, in patients with painful knee osteoarthritis (OA).

Methods

After a 1‐week nonsteroidal antiinflammatory drug washout period, patients received either diacerein or placebo for 3 months, followed by an off‐treatment period of 3 months to determine the carryover effects of the drug. Although patients were followed up through month 6, the primary efficacy end point was the percent change from baseline in pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A) at month 5 (i.e., 2 months after the end of treatment) compared with placebo. The co–primary efficacy end point was the percent change from baseline in the total WOMAC score, also at month 5 versus placebo.

Results

Two hundred three patients were screened, and 168 patients with painful knee OA were randomized. One hundred sixty‐five patients were analyzed in an intent‐to‐treat analysis. At month 5, diacerein showed statistically significant superiority versus placebo as assessed with both the WOMAC A (P < 0.0001) and the total WOMAC (P < 0.0001), demonstrating the carryover effect of the drug. This superiority was already evident from month 2 for pain (P = 0.001) and month 1 for total WOMAC (P = 0.0021). Diacerein was safe and well tolerated. No serious or previously undocumented adverse events were observed during the study.

Conclusion

This is the first published study of a symptomatic slow‐acting OA drug in which the time of assessment of the primary outcome end points was 2 months after the end of a 3‐month treatment period. The results show that diacerein is safe and effective for the treatment of knee OA and has a long carryover effect.

     

Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter,randomized, placebo‐controlled trial

Objective

To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA).

Methods

A multicenter, randomized, parallel‐group, placebo‐controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment.

Results

Eighty‐five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent‐to‐treat analysis (mean ± SD decrease 7.8 ± 24.9 mm with HA versus 9.1 ± 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events.

Conclusion

Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA.

     

A new marker for osteoarthritis: Cross‐sectional and longitudinal approach

Objective

To investigate the association between urinary concentrations of C‐telopeptide fragments of type II collagen (CTX‐II) and the prevalence and progression of radiographic osteoarthritis (OA) of the knee and hip.

Methods

The study population consisted of a sample of 1,235 men and women ages ≥55 years who were enrolled in the Rotterdam Study (a population‐based cohort study) and who were followed up for a mean of 6.6 years. Prevalent radiographic OA was defined as a Kellgren/Lawrence score ≥2; progression of radiographic OA was defined as a decrease in joint space width.

Results

Subjects with a CTX‐II level in the highest quartile had a 4.2‐fold increased risk of having radiographic OA of the knee (95% confidence interval [95% CI] 2.5–7.0) and of the hip (95% CI 2.2–7.8) compared with subjects with a CTX‐II level in the lowest quartile. We observed a substantially stronger association between CTX‐II levels and radiographic OA for subjects with hip pain (odds ratio [OR] 20.4, 95% CI 2.3–185.2) than for those without hip pain (OR 3.0, 95% CI 1.5–6.0). Subjects with a CTX‐II level in the highest quartile had a 6.0‐fold increased risk for progression of radiographic OA at the knee (95% CI 1.2–30.8) and an 8.4‐fold increased risk for progression of radiographic OA at the hip (95% CI 1.0–72.9). All of these associations were found to be independent of known risk factors for OA, such as age, sex, and body mass index.

Conclusion

This study shows that CTX‐II is associated with both the prevalence and the progression of radiographic OA at the knee and hip. Importantly, this association is independent of known clinical risk factors for OA and seems stronger in subjects with joint pain.

     

Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: A randomized,double‐blind,placebo‐controlled clinical trial at a single center

Objective

To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.

Methods

This investigator‐initiated, single‐center, randomized, double‐blind, placebo‐controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0–100‐mm visual analog scale (VAS) and functional impairment of at least 6 (0–30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent‐to‐treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy.

Results

There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores −8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores −2.14; P = 0.008). There was a statistically significant between‐group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups.

Conclusion

This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile.

     

Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: A randomized,double‐blind,placebo‐controlled trial

Objective

To evaluate the safety and efficacy of long‐term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).

Methods

In a randomized, double‐blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50‐foot walking time. Clinical symptoms were assessed just before each injection.

Results

At the 1‐year and 2‐year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid‐injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline‐injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2‐year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).

Conclusion

Our findings support the long‐term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long‐term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long‐term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.

     

Gabapentin in the treatment of fibromyalgia: A randomized,double‐blind,placebo‐controlled,multicenter trial

Objective

To assess the efficacy and safety of gabapentin in patients with fibromyalgia.

Methods

A 12‐week, randomized, double‐blind study was designed to compare gabapentin (1,200–2,400 mg/day) (n = 75 patients) with placebo (n = 75 patients) for efficacy and safety in treating pain associated with fibromyalgia. The primary outcome measure was the Brief Pain Inventory (BPI) average pain severity score (range 0–10, where 0 = no pain and 10 = pain as bad as you can imagine). Response to treatment was defined as a reduction of ≥30% in this score. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent‐to‐treat sample, with treatment‐by‐time interaction as the measure of effect.

Results

Gabapentin‐treated patients displayed a significantly greater improvement in the BPI average pain severity score (P = 0.015; estimated difference between groups at week 12 = −0.92 [95% confidence interval −1.75, −0.71]). A significantly greater proportion of gabapentin‐treated patients compared with placebo‐treated patients achieved response at end point (51% versus 31%; P = 0.014). Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity, the Patient Global Impression of Improvement, the Medical Outcomes Study (MOS) Sleep Problems Index, and the MOS Short Form 36 vitality score, but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale. Gabapentin was generally well tolerated.

Conclusion

Gabapentin (1,200–2,400 mg/day) is safe and efficacious for the treatment of pain and other symptoms associated with fibromyalgia.

     

Effects of long‐term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys

Objective

To determine the effects of long‐term estrogen replacement therapy (ERT) on the severity of osteoarthritis (OA) of the knee joint in surgically postmenopausal (bilaterally ovariectomized) female monkeys. A secondary aim was to evaluate the effect of soy phytoestrogen (SPE) treatment on the severity of OA.

Methods

Feral adult female cynomolgus macaques were ovariectomized bilaterally and then randomly divided into 3 age‐ and weight‐matched treatment groups. For 3 years, the first group received ERT with conjugated equine estrogens, the second group received SPE, and the third group received no treatment (controls). At necropsy, histologic lesions of OA were graded, and the area and thickness of cartilage and subchondral bone were measured. The data were summarized by principal components analysis, and the resulting factors and individual variables were compared using analysis of variance and analysis of covariance (age and weight as covariates).

Results

Cartilage lesions of OA were significantly less severe in the animals given ERT compared with those in the control group. This treatment effect remained significant when adjusted for age and weight. The factor representing subchondral bone was significantly higher, but the number of osteophytes was lower, in the ERT group compared with the control group. SPE treatment had no significant effect on cartilage or bone lesions of OA.

Conclusion

These results demonstrate that long‐term ERT significantly reduces the severity of OA lesions in this animal model.