Sulfasalazine in early rheumatoid arthritis. A 48-week double-blind, prospective, placebo-controlled study. Sulfasalazine in early rheumatoid arthritis. The Australian Multicentre Clinical Trial Group. Comparison of responses to and adverse effects of graded doses of sulfasalazine in the treatment of rheumatoid arthritis. 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. Sulfasalazine in the treatment of ankylosing spondylitis. A twenty-six-week, placebo-controlled clinical trial. Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine. Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. [Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind placebo-controlled study and comparison with other controlled studies]. The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years.
To investigate the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of early rheumatoid arthritis (RA).
                Eighty patients (symptomatic disease < 12 months) were randomly assigned to treatment with SSZ or placebo for 48 weeks. Clinical, laboratory, and scintigraphic data were used to determine the effects of treatment.
                SSZ was superior to placebo in reducing the laboratory features of inflammation, the clinical parameters of disease activity, as well as the scintigraphic activity in the joints. Furthermore, fewer erosive changes developed in the joints of patients receiving active treatment, but the difference between treatment groups did not reach statistical significance.
                SSZ is effective in the treatment of RA, and its onset of action is rapid. The results support the view that SSZ retards the development of joint erosions. However, like other conventional disease-modifying antirheumatic drugs, its remission-inducing ability is insufficient. One hundred and five patients with a diagnosis of early nonerosive rheumatoid arthritis (RA) were randomized to receive enteric coated sulfasalazine as Salazopyrin En-tabs or placebo for 6 months. Sixty-five patients completed this 6 month treatment period. Patients taking sulfasalazine were significantly better than those taking placebo in terms of Ritchie articular index, number of swollen and tender joints and erythrocyte sedimentation rate. The sulfasalazine group also demonstrated a significant fall in serum hyaluronic acid, IgM rheumatoid factor and C-reactive protein concentration. Side effects leading to withdrawal from treatment occurred in 14 of the sulfasalazine group and 4 of the placebo group. The most common side effects of patients taking sulfasalazine were rashes, liver function test abnormalities and gastrointestinal upsets. Our study demonstrates the efficacy of sulfasalazine in early RA. Sulfasalazine (0, 0.5, 1, or 2 g daily in divided doses) was given to patients with definite or classical rheumatoid arthritis (RA) insufficiently controlled by a nonsteroidal antiinflammatory drug. Grip strength, Westergren sedimentation rate, and physician and patient global assessment improved in those patients given 2 g/day. Inadequate response was the primary reason for withdrawal in the groups given placebo or 0.5 g/day, while adverse reactions (mainly gastrointestinal upset or rash) accounted for most withdrawals from the groups that received 1 or 2 g/day. Although its use is limited by adverse reactions, sulfasalazine is effective in the treatment of patients with RA. To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy.
                Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO).
                Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01).
                Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine. Eighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (less than or equal to 3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS. Radiographic disease progression with leflunomide and sulfasalazine treatment was assessed in rheumatoid arthritis patients in a double-blind trial that was placebo controlled for the first 6 months. Completers at 6 months opted to continue on 12- and 24-month double-blind extensions; patients in the placebo group were switched to sulfasalazine. Changes in Larsen scores were assessed in evaluable patient cohorts at 6 (n=228), 12 (n=136), and 24 (n=65) months. Changes in Larsen scores and erosive joint counts with leflunomide and sulfasalazine at 6 months showed significantly less radiographic progression than placebo. Sustained retardation of radiographic progression was seen in the 24-month intent-to-treat cohorts (delta Larsen scores: leflunomide -0.07, sulfasalazine -0.03). Changes in erosive joint counts within the 24-month leflunomide cohort suggest halting of disease progression for patients who continued in the study for 2 years (leflunomide -0.92, sulfasalazine 0.80). Leflunomide was well tolerated with no unexpected adverse events during the 2-year period. This study demonstrates that slowing of disease progression with leflunomide, observed as early as 6 months, is maintained long term in patients who complete 2 years of treatment. Psoriatic arthritis (PsA) is often poorly responsive to 2nd line antirheumatic drug therapy. Sulfasalazine has recently gained wide acceptance in the treatment of rheumatoid arthritis, and beneficial effects have also been noted in ankylosing spondylitis and reactive arthritis. We report a double blind placebo controlled study of sulfasalazine in PsA.
                Twenty-four patients with active PsA were randomized to receive either sulfasalazine (3 g/day) (n = 10) or placebo (n = 14) for 8 weeks, in a double blind manner, followed by an 8 week open label crossover phase for nonresponding placebo patients.
                Compared with placebo controls, sulfasalazine treated patients were significantly improved at Weeks 4 and 8 with respect to physician (p < 0.01) and patient (p < 0.05) global assessments. Duration of morning stiffness was significantly decreased at Week 8 (p < 0.01). Clinical variables of disease activity returned to baseline after a 4 week drug washout period in 5 evaluable patients. Six patients in the placebo group crossed over to an 8 week open label phase and demonstrated significant improvements in joint scores, 50 ft walking time, and global patient assessment. Sulfasalazine treated patients also showed significant improvements in cutaneous involvement.
                Sulfasalazine was effective in PsA, with efficacy observed as early as the 4th week of treatment. Longterm studies are needed to determine whether such therapy can modify disease outcome. To assess the efficacy and tolerability of sulfasalazine in ankylosing spondylitis including a meta-analysis of comparable trials.
                In a prospective, randomized, double-blind, placebo-controlled trial 70 patients with established diagnosis of ankylosing spondylitis and a mean disease duration of 16.7 years were investigated in two centers for 26 weeks comparing 3 g/d sulfasalazine to placebo.
                The main outcome parameters, pain score, fingers-to-floor test, and CRP, did not improve significantly in the sulfasalazine group compared to the placebo group. Altogether sulfasalazine was significantly superior to placebo only concerning the IgA levels. The dropout rate was 47% for the sulfasalazine group and 19% for the placebo group. Due to side effects, 38% and 11%, respectively, stopped treatment. Ten other prospective, double-blind, controlled studies were analyzed. Altogether 959 patients with a mean disease duration of 13.9 years were evaluated. Most parameters did not improve significantly in the sulfasalazine groups compared to the placebo groups. Spinal motility remained nearly unchanged (0.3-3.5% improvement). Pain, morning stiffness, functional index, and global assessment were slightly influenced (1.9-11.7%). Reduction of ESR, CRP, IgA, IgG, and IgM was more distinct (12.6-20.3%). In 4 studies SSZ had greater efficacy in patients with peripheral joint involvement.
                Sulfasalazine has no clinically relevant benefit in patients with ankylosing spondylitis. The dropout-rate due to adverse effects is high with a daily dose of 3 g. Sulfasalazine may be beneficial in peripheral joint involvement. Only few data exist about patients with a disease duration of less than 10 years. A 3-year placebo-controlled trial of sulphasalazine (SASP) in 89 patients with established AS (including radiological sacroiliitis) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility. Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients, but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years. The natural history of established AS suggested two groups of patients: the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis, and a minority who tend to have recurrent extra-spinal problems.
Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.