Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial

BACKGROUND: 5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer but it often causes diarrhoea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth. AIM: To determine if oral glutamine prevents changes in intestinal absorption (IA) and permeability (IP) induced by FU/FA. METHODS: Seventy chemotherapy naive patients with colorectal cancer were randomly assigned to oral glutamine (18 g/day) or placebo before the first cycle of FU (450 mg/m(2)) and FA (100 mg/m(2)) administered intravenously for five days. Treatment was continued for 15 days, starting five days before the beginning of chemotherapy. IA (D-xylose urinary excretion) and IP (cellobiose-mannitol test) were assessed at baseline and four and five days after the end of the first cycle of chemotherapy, respectively. Patients kept a daily record of diarrhoea, scored using the classification system of the National Cancer Institute (Bethesda, Maryland, USA). Duration of diarrhoea was recorded and the area under the curve (AUC) was calculated for each patient. RESULTS: Baseline patient characteristics and basal values of IP and IA tests were similar in the two arms. After one cycle of chemotherapy, the reduction in IA (D-xylose absorption) was more marked in the placebo arm (7.1% v 3. 8%; p=0.02); reduction of IP to mannitol was higher in the placebo arm (9.2% v 4.5%; p=0.02); and urinary recovery of cellobiose was not different between the study arms (p=0.60). Accordingly, the cellobiose-mannitol ratio increased more in the placebo arm (0.037 v 0.012; p=0.04). Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm. CONCLUSIONS: Glutamine reduces changes in IA and IP induced by FU and may have a protective effect on FU induced diarrhoea.     

Penicillamine in ankylosing spondylitis: a double blind placebo controlled trial

A double blind placebo controlled trial was carried out over a 6-month period on 17 patients with ankylosing spondylitis (AS) to assess the effect of the second line antirheumatic drug, D-penicillamine. The patients included 13 with peripheral joint involvement. No significant improvement over placebo was detected in a variety of clinical and laboratory indices in the patients receiving active treatment. This controlled trial would not support a use for penicillamine in AS.     

Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial

OBJECTIVE: To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS). METHODS: This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity. RESULTS: Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups. CONCLUSION: MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit.     

Budesonide treatment of collagenous colitis: a randomised,double blind,placebo controlled trial with morphometric analysis

BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. AIMS: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. PATIENTS: Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.     

英利昔单抗联合甲氨蝶呤治疗类风湿关节炎的随机双盲临床研究

目的评价英利昔单抗与甲氨蝶呤(MTX)联合使用与单独使用MTX,在治疗类风湿关节炎(RA)中的疗效与安全性。方法本研究为随机、双盲、平行对照的临床试验。49例接受过至少3个月稳定剂量MTX治疗的活动性RA患者随机分为试验组(24例)和对照组(25例)。两组受试者在第0、2、6、14周分别接受3mg/kg的英利昔单抗或安慰剂静脉滴注,同时每周按固定剂量继续服MTX。并于试验的第0、2、6、14、18周随访,评价疗效和不良反应。以美国风湿病学会(ACR)疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、晨僵时间、关节肿胀数、关节肿胀指数、关节压痛数、关节压痛指数；次要疗效指标为疼痛目视模拟测量表(VAS)评分、疲乏VAS评分、疾病总体状况的医生评价VAS评分、疾病总体状况的病人评价VAS评分、健康评价问卷(HAQ)评分。结果治疗后第2周时,英利昔单抗联合MTX组ACR20有效率为62．5%,对照组仅为8．0%(P=0．002)；晨僵时间、关节压痛数、关节压痛指数、关节肿胀数、关节肿胀指数、疼痛VAS、疲乏VAS、医生总体评价VAS、病人总体评价VAS、HAQ和血沉等较对照组也均有显著的改善(P＜0．05或P＜0．01)。第18周时,英利昔单抗联合MTX组ACR20有效率为79．2%,对照组只有48．0%(P=0．024)。两组之间不良事件发生率差异无统计学意义。结论英利昔单抗联合MTX治疗RA的疗效明显优于单用MTX的疗效,能迅速改善与RA有关的各项症状、体征和实验室炎性活动指标,具有良好的安全性。     

Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: a double blind, placebo controlled, randomised trial

BACKGROUND: The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H pylori eradication leads to worsened control of reflux disease. METHODS: Consecutive patients with weekly reflux symptoms were prospectively recruited for endoscopy and symptom evaluation. Patients were enrolled if they had H pylori infection and required long term acid suppressants. Eligible patients were randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given for eight weeks for healing of oesophagitis and symptom relief. This was followed by a maintenance dose of 10 mg daily for up to 12 months. The primary study end point was the probability of treatment failure within 12 months, which was defined as either incomplete resolution of symptoms or oesophagitis at the initial treatment phase, or relapse of symptoms and oesophagitis during the maintenance phase. Predictors of treatment failure were determined by Cox's proportional hazards model. RESULTS: A total of 236 GORD patients were screened and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group). Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15 patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had treatment failure. The 12 month probability of treatment failure was 43.2% (95% confidence interval (CI) 29.9-56.5%) in the HpE group and 21.1% (95% CI 9.9-32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional hazards model, after adjustment for the covariates age, sex, erosive oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at baseline, H pylori eradication was the only predictor of treatment failure (adjusted hazard ratio 2.47 (95% CI 1.05-5.85)). CONCLUSION: H pylori eradication leads to more resilient GORD.     

UVA-1 cold light treatment of SLE: a double blind, placebo controlled crossover trial

OBJECTIVE: Treatment of patients with systemic lupus erythematosus (SLE) often implies strong drugs with possibly serious side effects. Thus there is a need for new immunosuppressive treatments. Long wave ultraviolet A (UVA-1) cold light therapy is an anti-inflammatory, immunomodulatory treatment with a possible systemic effect and few side effects. In the current study low dose UVA-1 cold light treatment was tested to determine whether it reduces disease activity in SLE. METHODS: Eleven patients with SLE were treated with UVA-1 cold light treatment and a placebo light treatment in a double blind, placebo controlled, crossover study. In two consecutive 12 week periods the patients were treated in the first three weeks with UVA-1 and placebo treatment or vice versa. The primary variables were the SLE Disease Activity Index (SLEDAI) and SLE Activity Measure (SLAM). RESULTS: The mean SLAM and SLEDAI showed a significant decrease of 30.4% (p=0.0005) and 37.9% (p=0.016) respectively after three weeks of UVA-1 and a non-significant decline of 9.3% (p=0.43) and 12.2% (p=0.54) respectively after three weeks of placebo treatment. In this small trial the difference in reduction of the disease activity indices during UVA-1 compared with during placebo treatment failed to reach the conventional border of significance (p=0.07). The total score of quality of life measure RAND-36 did not improve significantly, but the subscore for vitality did improve. CONCLUSION: Low dose UVA-1 cold light treatment was strongly suggestive of lowering disease activity in this double blind placebo controlled study, and no side effects occurred.     

Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial

BACKGROUND: Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor alpha. AIM: In the first randomised placebo controlled trial of any drug for the treatment of PG, we have studied the role of infliximab in this disorder. SUBJECTS: Patients 18 years of age or older with a clinical diagnosis of PG were invited to take part. METHODS: Patients were randomised to receive an infusion of infliximab at 5 mg/kg or placebo at week 0. Patients were then assessed at week 2 and non-responders were offered open labelled infliximab. The primary end point was clinical improvement at week 2, with secondary end points being remission and improvement at week 6. RESULTS: Thirty patients were entered into the study. After randomisation, 13 patients received infliximab and 17 patients received placebo. At week 2, significantly more patients in the infliximab group had improved (46% (6/13)) compared with the placebo group (6% (1/17); p = 0.025). Overall, 29 patients received infliximab with 69% (20/29) demonstrating a beneficial clinical response. Remission rate at week 6 was 21% (6/29). There was no response in 31% (9/29) of patients. CONCLUSIONS: This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG. Open label treatment with infliximab also produced promising results. Infliximab treatment should be considered in patients with PG.     

Allele and antigen-specific treatment of rheumatoid arthritis: a double blind,placebo controlled phase 1 trial

OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.     

A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition

BACKGROUND AND AIMS: To determine whether the inclusion of 20 g free glutamine as part of the nitrogen source of parenteral feeds reduces length of hospital stay or mortality. METHODS: In a randomised, double blind, controlled trial in 168 patients clinically accepted for parenteral nutrition, standard feeds were compared with feeds in which 3.8 g of the total nitrogen was replaced with the equivalent 20 g glutamine. A minimum of 11 g nitrogen/day was used in all patients. Daily intakes of energy and nitrogen were determined using a validated computer protocol and were similar for the two groups. All feeds included trace elements, vitamins, electrolytes, and minerals. RESULTS: A total of 85 patients received a median of eight (interquartile range 5-13) daily feeds containing glutamine while 83 received a median of eight (5-15) standard feeds. No difference between groups was detected for infective complications. Twenty control patients and 14 who had received glutamine died during their hospital stay (NS). Median length of stay was 32 (23-52) days on glutamine, which was not significantly different from the control value of 35 (25-55) days. Glutamine was associated with a significant (p<0.03) reduction in length of stay in surgical patients (45 days (range 29-81) versus 30 days (range 19-54)). CONCLUSION: The benefit from glutamine supplementation of parenteral feeds as used in this trial has not been proved. Supplementation may have advantages in surgical patients and in haematological malignancy. Further trials are required.     

Campylobacter associated gastritis in patients with non-ulcer dyspepsia: a double blind placebo controlled trial with colloidal bismuth subcitrate.

Fifty consecutive patients with non-ulcer dyspepsia and a Campylobacter associated gastritis (CAG) were randomly assigned to treatment with colloidal bismuth subcitrate (CBS) 240 mg twice daily or placebo, according to a double blind study design. After the blind treatment an 'open' treatment with CBS was started in both groups. Twenty six patients treated with CBS showed a significant reduction in colonisation with Campylobacter pylori and a significant improvement in the Whitehead gastritis score. No significant changes were recorded in twenty four patients treated with placebo. After an additional course of CBS no further improvement in gastritis score was noted but there was a further reduction in Campylobacter colonisation. CBS did not greatly alter subjective complaints. Subjective complaints were improved in both treatment groups except for nausea and meteorism that improved more in the CBS treated patients. This finding again questions the clinical significance of gastritis and also casts doubt on the clinical relevance of therapeutical measures aimed at eradication of C pylori.     

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

OBJECTIVE: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. METHODS: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. RESULTS: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: -2.2 cm (95% CI, -2.6 to -1.7) and -2.0 cm (-2.5 to -1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: -2.1 (-2.6 to -1.6) and -1.6 (-2.2 to -1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). CONCLUSIONS: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability.     

Photodynamic therapy for dysplastic Barrett's oesophagus: a prospective, double blind, randomised, placebo controlled trial

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the action of light on a photosensitizing agent. We have assessed the potential use of PDT in the ablation of Barrett's oesophagus. METHODS: Thirty six patients with dysplastic Barrett's oesophagus receiving acid suppression medication with omeprazole were randomised to receive oral 5-aminolaevulinic acid (ALA) 30 mg/kg or placebo, followed four hours later by laser endoscopy. Follow up endoscopy was performed at one, six, 12, and 24 months. RESULTS: Of 18 patients in the ALA group, a response was seen in 16 (median decrease in area in the treated region 30%; range 0-60%). In the placebo group, a decrease in area of 10% was observed in two patients with no change in 16 (median 0%; range 0-10%; treatment v placebo, p<0.001). No dysplasia was seen in the columnar epithelium within the treatment area of any patient in the PDT group. However, in the placebo group, persistent low grade dysplasia was found in 12 patients (p<0.001). There were no short or long term major side effects. The effects of treatment were maintained for up to 24 months. CONCLUSIONS: This is the first randomised controlled trial of PDT for Barrett's oesophagus. It demonstrates that ALA induced PDT can provide safe and effective ablation of low grade dysplastic epithelium.     

Short term effects of ibuprofen in primary fibromyalgia syndrome: a double blind, placebo controlled trial

Therapeutic effects of ibuprofen were evaluated in 46 patients with primary fibromyalgia syndrome in a double blind, placebo controlled study for 3 weeks and in an open trial for another 3 weeks. Several features of primary fibromyalgia syndrome, including number of pain sites, fatigue, swelling feeling, and tender points significantly improved over time in both groups. However, no significant differences were found between the ibuprofen and placebo groups. Improvements in fibromyalgia features might have occurred as a result of physician or study interactions (i.e., an intervention effect). An important observation in our blinded study was that tender point sites among patients with fibromyalgia were significantly (p less than 0.001) consistent at 3 as well as 6 weeks when compared with the baseline.     

Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study

BACKGROUND: High dose growth hormone, glutamine, and a high carbohydrate diet may improve intestinal function in short bowel patients. AIMS: To investigate if growth hormone with glutamine and no change in diet improved intestinal function. PATIENTS AND METHODS: Eight short bowel patients were randomised in a double blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day) with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days. Balance studies were performed at baseline and five days after placebo and treatment were terminated. Dietary energy, carbohydrate, and fat were maintained as usual. RESULTS: Growth hormone with glutamine did not improve intestinal absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%), nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (-16%, -16%, -36%), potassium (43%, 47%, 33%), calcium (-16%, -16%, -15%) or magnesium (-3%, 4%, 2%) compared with placebo or baseline (p>0.05) five days after treatment was terminated. All patients experienced adverse effects. CONCLUSIONS: Combined high dose growth hormone and glutamine administered for four weeks did not improve intestinal absorption five days after treatment was terminated in short bowel patients on their usual diet.     

Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure. DESIGN--A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler). RESULTS--Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements. CONCLUSION--Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur.     

A double blind, multicentre, placebo controlled trial of lornoxicam in patients with osteoarthritis of the hip and knee.

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.     

Randomised, double blind, placebo controlled trial of inosine pranobex in rheumatoid arthritis.

In a randomised, placebo controlled, double blind study inosine pranobex was assessed as a possible second line drug in rheumatoid arthritis. Twenty four patients received inosine pranobex (3 g/day) and 26 patients received placebo for up to 24 weeks. Morning stiffness, articular index, grip strength, pain score, erythrocyte sedimentation rate, C reactive protein, IgG, IgM, and serum urate were assessed at weeks 0, 12, and 24. Baseline characteristics were similar except for a significantly higher C reactive protein in the placebo group. No significant improvement occurred in any variable: (a) when comparing week 0 with week 12 or week 24 for either group, (b) comparing active drug with placebo at week 12 or 24, or (c) taking all 50 patients as one group. Withdrawal from the study for lack of response or side effects was similar in both groups. Serum urate increased transiently but significantly with inosine pranobex (a recognised side effect). It is concluded that inosine pranobex has no second line activity in rheumatoid arthritis. Further, 50 patients effectively given placebo showed no spontaneous improvement in their disease activity.