Sulfasalazine In Patients Research Articles

Comparison of the effects of <i>Tripterygii totorum</i> and sulfasalazine on rheumatoid arthritis: A retrospective cohort study

Purpose: To compare, in a retrospective study, the effects and safety profiles of Tripterygii totorum and sulfasalazine in patients with rheumatoid arthritis (RA) following 24 weeks of treatment.
 Methods: RA patients (n = 164) who were treated with Tripterygii totorum or sulfasalazine from August 2012 to February 2016 were included in this study. The major end-point was ≥ 20 % improvement as per American College of Rheumatology (ACR) criterion (ACR 20 response) after 24 weeks. Moreover, ACR 50 and ACR 70 responses were studied. The safety parameters investigated comprised of adverse events, vital signs, as well as hematological and biochemical indices (blood counts, electrolyte levels, and kidney and liver function).
 Results: At 24 weeks, ACR 20 response was 57.32 % in patients on Tripterygii totorum, while the corresponding value in patients on sulfasalazine was 39.02 % (p = 0.02). In the Tripterygii totorum group, ACR 50 response was 41.46 %, while ACR 70 response was 29.27 %. In sulfasalazine group, ACR 50 response was identified in 26.83 % of the patients, while ACR 70 response was seen in 21.95 % of patients. Adverse events were greater in the Tripterygii totorum group than in sulfasalazine group.
 Conclusion: These results suggest that Tripterygii Totorum significantly mitigates RA, with a tolerable safety profile. However, there is need for long-term or controlled trials to ascertain the therapeutic potential of Tripterygii totorum in RA.
 Keywords: Traditional Chinese medicine, Tripterygii totorum, Sulfasalazine, Rheumatoid arthritis

Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents.

Background and aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases—within 100 days in 35 of these cases (83%). Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective.

Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2weeks as one cycle. Tumor biopsies were obtained before and after 14days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12g/day. Safety was confirmed up to a dosage of 12g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia.

Despite the demonstrated efficacy of etanercept for the treatment of ankylosing spondylitis (AS), sulfasalazine is often prescribed, especially in countries with limited access to biologic agents. The objective of this subset analysis of the ASCEND trial was to compare the efficacy of etanercept and sulfasalazine in treating patients with AS from Asia, Eastern/Central Europe, and Latin America. A total of 287 patients, 190 receiving etanercept 50 mg once weekly and 97 receiving sulfasalazine 3 g daily, from eight countries were included in this subset analysis. Differences in disease activity and patient-reported outcomes assessing health-related quality-of-life (HRQoL) parameters in response to treatment were analyzed using the Cochran-Mantel-Haenszel test for categorical efficacy endpoints and analysis of covariance model for continuous variables. At week 16, a significantly greater proportion of patients receiving etanercept achieved ASAS20 (79.0 %) compared with patients receiving sulfasalazine (61.9 %; p = 0.002). At week 16, treatment with etanercept also resulted in significantly better responses than sulfasalazine for ASAS40 (64.7 vs. 35.1 %; p < 0.001), ASAS5/6 (48.1 vs. 26.3 %; p < 0.001), proportion of patients achieving 50 % response in Bath AS Disease Activity Index (65.8 vs. 42.3 %; p < 0.001), partial remission (35.3 vs. 17.5 %; p = 0.002), and all HRQoL parameters. Both treatments were well tolerated. Etanercept was significantly more effective than sulfasalazine in the treatment of patients with AS from Asia, Central/Eastern Europe, and Latin America.

Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.

Efficacy and safety of sulfasalazine in patients with chronic idiopathic urticaria

BackgroundThere are limited data regarding alternative treatments for antihistamine refractory chronic idiopathic urticaria (CIU). Patients with recalcitrant skin disease often cannot gain satisfactory symptom control with standard therapies and may require prolonged courses of oral corticosteroids. There is a lack of information describing the degree and duration of sulfasalazine's efficacy, the frequency and nature of adverse reactions, and the appropriate safety monitoring parameters. ObjectiveTo present a case series detailing the efficacy and safety of sulfasalazine therapy in patients with CIU. MethodsA retrospective chart review was conducted of 39 patients with sulfasalazine-treated CIU evaluated at Johns Hopkins Asthma and Allergy Center from October 2007 to March 2012. Eight patients were excluded from the final analysis. ResultsTwenty-six patients (83.9%) showed an improvement in symptoms within the first 3 months, with 51.6% of patients (n = 16) becoming asymptomatic within the first 6 months of starting sulfasalazine. Eleven patients (35.4%) achieved complete relief of symptoms after tapering off sulfasalazine therapy. Five of the 31 patients (16.1%) failed treatment, defined as worsening symptoms and pursuit of an alternative therapy. Six of 31 patients (19.4%) had a modified course of sulfasalazine therapy owing to abnormal hematologic parameters. Serious adverse events leading to drug discontinuation occurred in 6.5% of patients (n = 2) and included a patient with drug-induced leukopenia and one with rhabdomyolysis. ConclusionSulfasalazine is a highly effective treatment for patients with antihistamine resistant CIU. The frequency of adverse events leading to an alteration of sulfasalazine treatment supports the need for close monitoring of these patients.

Effets indésirables de la sulfasalazine : discussion de leur mécanisme et du rôle de la composante sulfamidée

Sulfasalazine is widely used in the treatment of chronic inflammatory bowel disease (IBD) and certain rheumatic diseases. However, its use is associated with a high rate of adverse effects (AEs) which can be cutaneous, hematological, renal, hepatic, gastrointestinal or neurological. The aim of our study was to collect all cases of AEs suspected to be associated with the use of sulfasalazine in patients hospitalized in the department of Gastroenterology from the Hospital Hedi Chaker of Sfax (Tunisia) for a period of 5 years and to search the incriminated fraction (sulfonamide or salicylate). Our study population included 69 patients who received sulfasalazine for the treatment of IBD. We collected, in 23 patients (33%), 25 AEs suspected to be related to sulfasalazine. Cutaneous and hematological reactions are the most common. The subsequent administration of mesalazine was performed in 15 patients. It was well tolerated in 14 patients. So we were suspecting probably the responsibility of sulfonamide fraction in these cases. The mechanism of sulfasalazine induced AEs may be toxic or immunoallergic with the possibility of a cross-reaction with the other antimicroacterial sulfonamides.

Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: A randomized, double-blind trial

Etanercept, a fully human tumor necrosis factor (TNF) receptor, is an effective treatment in patients with ankylosing spondylitis (AS). Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS, and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present. Until now, no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine. This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS. In this randomized, double-blind study, patients received etanercept 50 mg once weekly (n=379) or sulfasalazine titrated to a maximum of 3 gm/day (n=187) for 16 weeks. The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) at 16 weeks. Last observation carried forward was predefined for imputation of missing values. The mean age of the patients was 41 years, 74% were male, and the mean disease duration was 7.6 years. The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine (75.9% versus 52.9%; P<0.0001). As early as week 2 of treatment, etanercept was found to be more effective than sulfasalazine (P<0.0001) in ameliorating both the axial symptoms and peripheral manifestations. Serious adverse events rarely occurred, and the rate of serious adverse events did not differ between groups. In this population of patients with AS, etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints.

Azathioprine and Ulcerative Colitis: A “Second-Look” Meta-Analysis

Dear Editor, We read with interest the article by Leung et al., a systematic review and meta-analysis of the efficacy of azathioprine in maintaining clinical remission in ulcerative colitis [1]. Since its publication, this article has been cited at local and national educational conferences as a synthesized estimate of the efficacy of azathioprine in maintenance of remission in ulcerative colitis. We embarked on replicated statistical analysis, analogous to a ‘‘secondlook’’ endoscopy, in order to provide clinicians and investigators with another perspective on employing the statistical tool of meta-analysis in the study of comparative effectiveness. Our conclusion is that there is not sufficient homogeneity to warrant a conclusion in either direction. We advocate for employing meta-analysis here as a closer look at the differences in this small number of individual studies rather than as an attempt to estimate a pooled effect of azathioprine. The choice of metrics, heterogeneity of controls, small sample size, and pitfalls of quality score reporting are important ingredients in this analysis. The choice of metric in a meta-analysis is important and should address the clinical question. In this meta-analysis, the relative risk metric showed a lack of statistical significance of a difference between the effect of azathioprine and controls at the greater than 95% confidence level in the random effects model, yet not in the fixed effects model. On our reexamination of the data, the log risk ratio difference, risk difference, and arc sine difference metrics all showed a small significant advantage of azathioprine over controls in fixed effects models. The risk difference metric showed a significant advantage of azathioprine over controls in a random effects model; however, the other metrics did not (Fig. 1). Overall, the authors’ conclusion of a trend toward efficacy based on limited data is supported by these analyses. However, the significance of this trend depends on which metric and model are utilized. There was significant heterogeneity in the control groups and response rates. Whereas random effects models may be able to account for unmeasured sources of heterogeneity among studies, the comparison here of a treatment to either placebo [2–4] or an active control [5, 6] is analogous to comparing major league baseball batters to a group of minor and little league batters. The efficacy of these controls ranged from 19 to 64%, i.e. two studies ranged from 19 to 23%, one study 44%, and two studies 62–64%. Compounding these differences in control rates, the studies compare therapies in patients with different levels of severity and length of disease (steroid-dependent [5], mild-to-severe [2], severe [3, 6], and newly diagnosed/ severe [4]). An example of how these factors confound the analysis is the inclusion of the study by Sood et al. in 2003 [6] in an estimate of average effect of azathioprine where the control rate of response was 62%. This study compares azathioprine and sulfasalazine in patients with newly diagnosed ulcerative colitis who often respond to first-line high-dose 5-aminosalicylic acid therapy alone. Removing this study from the meta-analysis, the relative risk random effects models now shows a significant advantage of azathioprine over controls (Fig. 2). B. G. Levesque (&) Center for Health Policy/Primary Care and Outcomes Research and Division of Gastroenterology, Stanford University School of Medicine, 117 Encina Commons, Stanford, CA 94305, USA e-mail: bglevesq@stanford.edu

Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study

Objective:To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy.Methods:Patients were randomly assigned to etanercept (25 mg...

Spondylarthropathies et médicaments anti-TNFα

Spondylarthropathies are a heterogeneous group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondylarthropathies. These diseases are characterised by inflammation in the spine, sacroiliac joints, entheses, peripheral joints, and a strong association with HLA-B27; they may cause severe destruction and/or ankylosis in a minority of patients. Conventional treatment includes non steroidal anti-inflammatory drugs, corticosteroid injections, and DMARDs such as sulfasalazine in patients with peripheral arthritis. TNFalpha appears as an important actor in the pathogenesis of spondylarthropathies. Among the anti-TNFalpha drugs, etanercept and infliximab have proved to be effective in the symptomatic treatment of ankylosing spondylitis and psoriatic arthritis. A clinical relapse was observed within a few weeks after treatment discontinuation in a majority of patients. Potential beneficial effects on the destructive and/or ankylosing evolution remains to be confirmed. Patients with active, severe and refractory spondylarthropathies are potential candidates for treatment with anti-TNFalpha drugs. Taking into account not only the efficacy but also the side effects, with rare but potentially severe complications such as tuberculosis or other opportunistic infections, and the relatively high cost of these drugs, preliminary criteria for the initiation, monitoring and discontinuation of these drugs in the treatment of spondylarthropathies were proposed. Long-term follow-up in large populations of patients with spondylarthropathies is necessary to better define the benefit/risk/cost ratio of anti-TNFalpha drugs.

Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis

To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC). Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106 patients in 1993-1995, and 122 patients in 2000-2002, they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups. The short-term efficacy and safety of SASP 3 g per d were evaluated. Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4% and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P<0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P<0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P<0.05). Rough and granular mucosa (67.9% vs 43.4%, P<0.05) and polyps (47.2% vs 32.8%, P<0.05) were identified in 1990s group more than in 2000s group. There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%, respectively. In 79 patients with clinical remission, 58.2% and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were better than in chronic relapse type (complete remission in 3, 7.5%; partial remission in 16, 40.0%; and improvement in 15, 37.5%) and chronic persistent type (complete remission in 1, 5.9%; partial remission in 6, 35.3%; and improvement in 6, 35.3%) respectively (P<0.05). In 110 patients treated with SASP, 18 patients (16.4%) had adverse reactions. Except for two cases of urticaria and one case of WBC decrease, none of the patients had to stop the treatment because of severe adverse reactions. Patients with mildly and moderately active UC in 2000s group had a shorter disease course, milder clinical manifestations, more first episode type and higher frequency of acute mucosal lesions in colonoscopy than in 1990s group. The patients in 1990s group had higher proportion of chronic relapse type and chronic mucosal change in colonoscopy than in 2000s group. The short-term efficacy of SASP could be mainly remission of clinical manifestations. But more than half of the patients still had light inflammation in colonoscopy and histology. The overall effects of SASP in first episode type were better than those in other types. SASP was a safe and effective drug to treat mildly and moderately active UC.

N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis

OBJECTIVES: 5-Aminosalicylate is metabolized in colonic mucosa by N-acetyltransferase 1 (NAT1), and sulfapyridine is metabolized in the liver by N-acetyltransferase 2 (NAT2). Common genetic polymorphisms in these enzymes result in rapid and slow acetylation. We determined the association between NAT1 genotype and response to mesalamine and sulfasalazine, as well as between NAT2 genotype and toxicity to sulfasalazine, in a population-based cohort of patients with ulcerative colitis. METHODS: DNA was obtained from 77 white patients with ulcerative colitis from Olmsted County, MN. NAT1 and NAT2 genotyping was performed using microelectronic array devices. Phenotypes were deduced from previously published genotype/phenotype correlations. Clinical response to mesalamine and sulfasalazine, and toxicity to sulfasalazine, were determined by medical record review and associated with NAT1 and NAT2 genotypes. RESULTS: The clinical response rates among 52 patients treated with mesalamine were 67% (31 of 46) for rapid acetylators and 83% (five of six) for slow acetylators (odds ratio = 0.4, 95% CI = < 0.1–3.9, p = 0.65). Similarly, the clinical response rates among 64 patients treated with sulfasalazine were 74% (43 of 58) for rapid acetylators and 67% (four of six) for slow acetylators (odds ratio = 1.4, 95% CI = 0.2–8.6, p = 0.65). The toxicity rates among the 64 patients treated with sulfasalazine were 34% (12 of 35) for slow acetylators and 45% (13 of 29) for rapid acetylators (odds ratio = 0.6, 95% CI = 0.2–1.8, p = 0.65). CONCLUSIONS: NAT1 and NAT2 genotypes did not predict response to mesalamine or sulfasalazine, or toxicity to sulfasalazine.

N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis.

5-Aminosalicylate is metabolized in colonic mucosa by N-acetyltransferase 1 (NAT1), and sulfapyridine is metabolized in the liver by N-acetyltransferase 2 (NAT2). Common genetic polymorphisms in these enzymes result in rapid and slow acetylation. We determined the association between NAT1 genotype and response to mesalamine and sulfasalazine, as well as between NAT2 genotype and toxicity to sulfasalazine, in a population-based cohort of patients with ulcerative colitis. DNA was obtained from 77 white patients with ulcerative colitis from Olmsted County, MN. NAT1 and NAT2 genotyping was performed using microelectronic array devices. Phenotypes were deduced from previously published genotype/phenotype correlations. Clinical response to mesalamine and sulfasalazine, and toxicity to sulfasalazine, were determined by medical record review and associated with NAT1 and NAT2 genotypes. The clinical response rates among 52 patients treated with mesalamine were 67% (31 of 46) for rapid acetylators and 83% (five of six) for slow acetylators (odds ratio = 0.4, 95% CI = < 0.1-3.9, p = 0.65). Similarly, the clinical response rates among 64 patients treated with sulfasalazine were 74% (43 of 58) for rapid acetylators and 67% (four of six) for slow acetylators (odds ratio = 1.4, 95% CI = 0.2-8.6, p = 0.65). The toxicity rates among the 64 patients treated with sulfasalazine were 34% (12 of 35) for slow acetylators and 45% (13 of 29) for rapid acetylators (odds ratio = 0.6, 95% CI = 0.2-1.8, p = 0.65). NAT1 and NAT2 genotypes did not predict response to mesalamine or sulfasalazine, or toxicity to sulfasalazine.

Immunomodulating drugs in the management of psoriatic arthritis.

Psoriatic arthritis is a chronic inflammatory arthropathy which can be distinguished from rheumatoid arthritis on the basis of differing patient demographics, genetic predisposition, histopathologic change, radiographic appearance, and clinical course. The cause of psoriatic arthritis remains unknown but appears to be autoimmune in nature as its pathogenesis is characterized by persistent synovial inflammation resulting in damage to the articular cartilage and osteolysis. Compared with rheumatoid arthritis, distinct lymphocyte subpopulations and pro-inflammatory cytokine levels appear to be present within the joint but the importance and therapeutic implications of these differences is uncertain. The clinical presentation of psoriatic arthritis is variable and overlapping patterns of joint involvement affecting both the appendicular and axial skeleton are seen. For patients with mild synovial disease and a favorable prognosis, the use of a nonsteroidal anti-inflammatory drug for symptomatic relief is often sufficient. However, the destructive potential of psoriatic arthritis is increasingly recognized and patients with more synovial disease and radiographic change at presentation appear to be at risk for greater morbidity and increased mortality. Immunomodulating therapy has the potential to suppress joint inflammation and preserve functional capacity but true disease modification has yet to be shown. The toxicity associated with presently available immunomodulatory agents makes careful patient selection and conscientious monitoring essential. The efficacy of methotrexate and sulfasalazine in patients with psoriatic arthritis is well defined while more anecdotal reports of benefit exist for other agents including the antimalarials, azathioprine, colchicine, cyclosporine, and the retinoids. For all treatment regimens, the magnitude of clinical improvement demonstrated to date has been rather small and quite subjective in character with few controlled studies of adequate size and duration having been reported. Emerging biologic therapies, such as those which target tumor necrosis factor, will hopefully provide future treatment options with greater efficacy and improved safety for patients with psoriatic arthritis.

Comparison of ω-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil ω-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or ω-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil ω-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 ± 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or ω-3 fatty acids (5.4 g/d) for 2 mo. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with 15N-glycine). Treatment with ω-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with ω-3 fatty acids in patients with mild to moderate active ulcerative colitis.

NAT2 genotyping and efficacy of sulfasalazine in patients with chronic discoid lupus erythematosus.

Sulfasalazine is an effective agent for chronic discoid lupus erythematosus (CDLE) but the response to treatment is considerably variable between patients and is also unpredictable. The reason for this might relate to differences in metabolism of the drug which is extensively acetylated by the polymorphic enzyme N-acetyltransferase 2 (NAT2). To test this possibility, the N-acetylation phenotype of eleven patients with CDLE and treated by standard doses of sulfasalazine was retrospectively determined by genotyping. A clear-cut difference in the outcome of treatment was observed according to whether the patients were slow acetylators (SA) or rapid acetylators (RA). Eight out of 11 patients responded to treatment with a complete or marked remission of the disease. Seven of them were RA. The three other patients who did not respond at all to the drug were SA. In addition, SA seem to be more prone to toxic events. These findings strongly suggest that the genetic polymorphism of NAT2 is responsible for differences in the response to sulfasalazine in patients with CDLE. Therefore, candidates for sulfasalazine therapy should be genotyped to identify those patients who might benefit from the drug.

The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis.

The pharmacokinetic disposition of sulfasalazine and its metabolites was studied in 8 young and 12 elderly patients with active rheumatoid arthritis. Equal numbers of slow and fast acetylators were included in each age group. Patients received enteric-coated sulfasalazine 2g daily for 21 days; specimens of serum and urine were collected for 96 h after administration on days 1 and 21. The elimination half-life of sulfasalazine was greater in the elderly patients. Many disposition parameters of sulfapyridine differed in slow and fast acetylators; of greatest significance were the increased values of steady-state serum concentration in the slow acetylators. There was no effect of age on any sulfapyridine disposition parameters. Values for the steady-state serum concentrations of N-acetyl-5-acetylsalicylic acid were greater in elderly than in young patients. The metabolism of sulfapyridine was markedly affected by acetylator phenotype and this was reflected in the composition of sulfapyridine-related material in the urine. Thus, age is a determinant of the steady-state concentrations of salicylate moieties but acetylator phenotype plays a greater role in determining the serum concentration of sulfapyridine, which has greater therapeutic implications in rheumatology.

Ankylosing spondylitis. Current drug treatment.

The administration of drugs constitutes an important component of the therapeutic programme in ankylosing spondylitis (AS). The main objective of initiating such therapy is to reduce pain, stiffness and discomfort. There are at present 3 groups of drugs available for the management of AS. The first group is represented by drugs thought to influence the disease process itself. In this group, sulfasalazine is the only drug which is controlled trials has been shown to suppress disease activity in AS. We recommend the use of sulfasalazine in patients with high disease activity, with peripheral arthritis and in those with AS of short duration. The second group of drugs includes nonsteroidal anti-inflammatory drugs (NSAIDs), which suppress inflammation without influencing the disease process. These drugs should be administered selectively during periods of high disease activity. Moreover, 1 drug should be used in appropriate dosage before it is assumed to be inefficient. High doses of NSAIDs may be prescribed before bedtime in patients suffering from severe pain and stiffness during the night. The toxicity profile of NSAIDs includes gastrointestinal and renal side effects. The third group comprises analgesics and muscle relaxants. Such drugs should be used rather frequently in patients with longstanding AS refractory to treatment with NSAIDs. Peripheral arthritis and enthesopathy are generally managed by local injections of corticosteroids, while AS complicated by psoriasis or inflammatory bowel disease is treated as primary AS. AS occurring in juveniles is best treated with aspirin and an NSAID, although careful observation is necessary for the development of Reye's syndrome (with aspirin) and gastric irritation (with NSAIDs). When patients with AS undergo surgery, the possibility of silent gastrointestinal bleeding due to the use of NSAIDs and salicylates should not be ignored. Patients treated with oral corticosteroids should receive a bolus injection of soluble corticosteroid prior to surgical intervention. NSAIDs may be administered pre- and postoperatively to relieve stiffness induced by immobility. Rapid treatment of intervening infections and use of NSAIDs is recommended in AS complicated by renal amyloidosis. During pregnancy and lactation, ibuprofen may be the preferred drug in AS.