Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Sulphasalazine in the management of psoriatic arthritis. The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years. Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study. Which is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study. Two exercise interventions for the management of patients with ankylosing spondylitis: a randomized controlled trial. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Sulfasalazine in early rheumatoid arthritis. A 48-week double-blind, prospective, placebo-controlled study. Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis. [Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind placebo-controlled study and comparison with other controlled studies]. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study.
To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy.
                Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments.
                While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints.
                SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients. There are few 'second-line' drugs available for the treatment of PSA and their use is often limited by toxicity. Thirty-nine patients with active PSA recruited from two rheumatology units were randomly allocated to either enteric-coated sulphasalazine (SASP) or placebo and followed for 24 wk. Six patients in the SASP group and 11 on placebo discontinued therapy before 24 wk. Evaluation of effect of treatment revealed significant improvements in articular index in both groups at 12 wk. By 24 wk the articular index in placebo group was still showing benefit. In addition to articular index the SASP group improved significantly in terms of visual analogue scale, duration of morning stiffness and ESR. SASP is effective in PSA but the partial clinical response to placebo indicates the importance of placebo-controlled studies in this variable disease. 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. A prospective double-blind, placebo-controlled, randomized study of 24 weeks duration was carried out comparing the efficacy and tolerability of sulphasalazine (SSZ) versus placebo in patients with psoriatic arthritis. A total of 120 patients were included in nine centres. All patients had active disease and fulfilled the criteria of definite psoriatic arthritis of at least 3 months duration. They received either SSZ (2.0 g/day) or placebo. Efficacy variables included pain, patient's overall assessment of joint and skin improvement, morning stiffness, Ritchie articular index, ESR and CRP. An intention-to-treat (ITT) analysis was performed for the 117 patients who qualified (three patients did not qualify due to missing data after baseline). A per-protocol analysis was performed for the 81 patients who completed the 6 months study period (SSZ = 38, placebo = 43). Major reasons for withdrawal were inadequate response (SSZ = 4, placebo = 7) and adverse events (SSZ = 8, placebo = 12). Pain was the only statistically significantly different primary outcome variable at end point in favour of SSZ in the ITT analysis. No significant differences were present in other clinical or biological variables, although there was a trend in favour of SSZ for some variables. SSZ, at a dose of 2.0 g/day, appeared to be a safe treatment in patients with psoriatic arthritis. At this dosage, its efficacy was only demonstrated for the pain variable. To compare the efficacy of sulfasalazine (SSZ) with its two moieties, 5-aminosalicylic acid (ASA) and sulfapyridine (SP), in patients with active ankylosing spondylitis (AS).
                A 26-week randomized, observer-blinded, 2-center, controlled study of treatment with either SSZ, ASA, or SP was conducted in 90 patients with active AS. Patients were evaluated at baseline and at monthly intervals, using several clinical and laboratory measures of disease activity. A global assessment of treatment efficacy was made by both patients and observers at the end of the study period.
                There were no significant changes in any of the parameters of disease activity in the ASA treatment group. Levels of serum IgG, IgA, and IgM fell significantly during treatment with SP, but none of the other changes reached statistical significance. Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ, as did nocturnal spinal pain and overall spinal pain. Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment.
                SP appears to be the active moiety in AS, although there was a trend suggesting a better outcome in the SSZ group compared with the SP group, perhaps suggesting the importance of a common sulfonamide structure for efficacy. The purpose of this clinical trial was to evaluate the impact of a 4-month comprehensive protocol of strengthening and flexibility exercises developed by our research group versus conventional exercises for patients with Ankylosing Spondylitis (AS) on functional and mobility outcomes.
                Randomized controlled trial. Forty-five patients diagnosed with AS according to the modified criteria of New York were allocated to control or experimental groups using a random numbers table. The control group was treated with a conventional protocol of physical therapy in AS, whereas the experimental group was treated with the protocol suggested by our research group. The conventional intervention consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the shortened muscles; and chest expansion exercises. The experimental protocol is based on the postural affectation of the AS and the treatment of the shortened muscle chains in these patients according to the Global Posture Reeducation (GPR) method. This intervention employs specific strengthening and flexibility exercises in which the shortened muscle chains are stretched and strengthened. The study lasted 4 mos. During this period, patients received a weekly group session managed by an experienced physiotherapist. Each session lasted an hour, and there were 15 total sessions. Changes in activity, mobility, and functional capacity were evaluated by an assessor blinded to the intervention, using the following previously validated scores from the Bath group: BASMI (tragus to wall distance, modified Schober test, cervical rotation, lumbar side flexion, and intermalleolar distance), BASDAI (The Bath Ankylosing Spondylitis Disease Activity Index), and BASFI (The Bath Ankylosing Spondylitis Functional Index).
                Both groups showed an improvement (prepost scores) in all the outcome measures, mobility measures of the BASMI index, as well as in BASFI and BASDAI indexes. In the control group, the improvement in tragus to wall distance (P=0.009) and in lumbar side flexion (P=0.02) was statistically significant. Although the rest of the outcomes also improved, they did not reach a significant level (P>0.05). In the experimental group, the improvement in all the clinical measures of the BASMI index (P<0.01) and in the BASFI index (P=0.003) was statistically significant. The intergroup comparison between the improvement (prepost scores) in both groups showed that the experimental group obtained a greater improvement than the control group in all the clinical measures of the BASMI index, except in tragus to wall distance, as well as in the BASFI index.
                The experimental protocol developed by our research group, based on the GPR method and specific strengthening and flexibility exercises of the muscle chains, offers promising results in the management of patients suffering from AS. Further trials on this topic are required. To assess the efficacy of a cannabis-based medicine (CBM) in the treatment of pain due to rheumatoid arthritis (RA).
                We compared a CBM (Sativex) with placebo in a randomized, double-blind, parallel group study in 58 patients over 5 weeks of treatment. The CBM was administered by oromucosal spray in the evening and assessments were made the following morning. Efficacy outcomes assessed were pain on movement, pain at rest, morning stiffness and sleep quality measured by a numerical rating scale, the Short-Form McGill Pain Questionnaire (SF-MPQ) and the DAS28 measure of disease activity.
                Seventy-five patients were screened and 58 met the eligibility criteria. Thirty-one were randomized to the CBM and 27 to placebo. Mean (S.D.) daily dose achieved in the final treatment week was 5.4 (0.84) actuations for the CBM and 5.3 (1.18) for placebo. In comparison with placebo, the CBM produced statistically significant improvements in pain on movement, pain at rest, quality of sleep, DAS28 and the SF-MPQ pain at present component. There was no effect on morning stiffness but baseline scores were low. The large majority of adverse effects were mild or moderate, and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group.
                In the first ever controlled trial of a CBM in RA, a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment. Whilst the differences are small and variable across the population, they represent benefits of clinical relevance and show the need for more detailed investigation in this indication. 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. We investigated the effects of home-based daily exercise on joint mobility, functional capacity, pain, and depression in patients with ankylosing spondylitis (AS). The patients were randomly assigned to a wait-list control group or to an exercise-therapy group. The exercise-therapy group performed a 20-min exercise program once per day for 8 consecutive weeks. After 8 weeks, compared with the control group, the exercise group showed improvements in joint mobility (cervical flexion, extension, shoulder flexion, abduction, hip abduction, and knee flexion), finger-floor distance, and functional capacity. Pain and depression scores were significantly lower after the exercise program in the exercise group than in the control group. These findings indicate that exercise therapy increases joint mobility and functional capacity, and decreases pain and depression in patients with AS. Home-based exercise, which is easily accessible to patients, might be an effective intervention for AS. 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. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy.
                Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments.
                Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea.
                SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.
Across all AS patients, SSZ demonstrated some benefit in reducing ESR and easing morning stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, patient and physician global assessment. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ.