Sulphasalazine in psoriatic arthritis: a double-blind placebo-controlled study. Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. Sulphasalazine in the management of psoriatic arthritis. Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy. Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study. Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial.
Sulphasalazine (SASP) is now accepted as an effective slow-acting antirheumatic drug for treating active rheumatoid arthritis (RA), but has not been previously evaluated in psoriatic arthritis. An earlier open study suggested that it was well tolerated and potentially beneficial. The present double-blind placebo-controlled trial of 30 patients has now confirmed its efficacy. Greater improvement occurred in those patients on active treatment than on placebo, with more benefit being detected in those patients with the symmetrical polyarticular but seronegative pattern of arthritis associated with a high acute-phase response. SASP was stopped in 26% because of side-effects but these were mild. No exacerbation or remission of psoriasis was observed. Further studies are in progress to determine the degree of efficacy of SASP in different clinical subgroups of psoriatic arthritis. Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP.
                A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS.
                At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy.
                In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies. Thirty-seven patients with psoriatic arthritis were entered into a 12-week prospective, controlled, double-blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5-5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate-treated patients. No patients were withdrawn from the study for adverse drug effects. 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. Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs.
                We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity.
                Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity.
                In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine. 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. To compare efficacy, toxicity, and the pharmacokinetics of the combination of sulphasalazine (SASP) and methotrexate (MTX) vs MTX alone in the treatment of SASP-resistant RA we conducted a controlled open clinical trial. Forty RA patients with active arthritis despite adequate SASP therapy, were allocated randomly to regimes of either SASP+MTX or MTX alone. The patients were evaluated openly by a single observer for 24 weeks. In the first 15 patients using the combination, pharmacokinetics of MTX without and with SASP were studied. Thirty-eight patients completed the trial. The mean decrease in the disease activity score in the group of patients receiving the combination was significantly greater than in the MTX group (-2.6 vs -1.3 respectively). The same pattern was seen concerning the other efficacy variables. There was no difference in the occurrence of toxicity. SASP had no influence on the pharmacokinetics of MTX. In conclusion in this open study the efficacy of the combination of MTX and SASP seems to be superior to MTX alone, the toxicity of both therapies was similar. This effect was not explained by the pharmacokinetics of MTX which were not altered by concomitant SASP administration. 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. Treatment of psoriatic nail is difficult.
                The aim of this study was to evaluate and compare the efficacy and safety of methotrexate and cyclosporine in psoriatic nail.
                Thirty-seven psoriatic patients with nail involvement were randomized to treatment with methotrexate (initial dose, 15 mg per week) or cyclosporine (initial dose, 5 mg per kg of bodyweight per day) for 24 weeks. The primary outcome was the Nail Psoriasis Severity Index (NAPSI). The Psoriasis Area and Severity Index (PASI), doctor and patient global score were also measured. The scores were determined by a blinded observer.
                Seventeen patients completed the study in each group. The mean percentages of reduction of the NAPSI score after methotrexate and cyclosporine treatments were 43.3% and 37.2%, respectively. No significant differences between the treatment groups was found for in the NAPSI, PASI, physician's and patient's global score at the end of the study period. The methotrexate group showed a significant improvement in nail matrix scores and the cyclosporine group in nail bed score.
                Moderate effectiveness on psoriatic nail was found in the two treatment agents and there were no significant differences in efficacy between the groups. A significant improvement was detected in methotrexate group for the nail matrix findings, and in cyclosporine group for the nail bed findings.
                © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology. To investigate the potential clinical benefit of a combination therapy.
                205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
                The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
                This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable. To compare the efficacy of sulphasalazine, methotrexate, and the combination of both in patients with early rheumatoid arthritis (RA), not treated with disease-modifying anti-rheumatic drugs previously, we conducted a double-blind, double-dummy, controlled, clinical trial. One hundred and five patients with active, early RA, rheumatoid factor and/or HLA DR1/4 positive were randomized between sulphasalazine (SSZ) 2000 (maximum 3000) mg daily, or methotrexate (MTX) 7.5 (maximum 15) mg weekly, or the combination (COMBI) of both, and were followed up by a single observer for 52 weeks. The mean change over time per patient, including all visits, in Disease Activity Score (DAS) was: SSZ: -1.6 (95% CI -2.0 to -1.2); MTX: -1.7 (-2.0 to -1.4); COMBI: -1.9 (-2.2 to -1.6); the difference week 0-week 52 (SSZ, MTX, COMBI respectively); DAS: -1.8, -2.0, -2.3, Ritchie articular index: -9.2, -9.5, -10.6, swollen joints: -9.2, -12.4, -14.3, erythrocyte sedimentation rate: -17, -21, -28. Nausea occurred significantly more in the COMBI group. The numbers of drop-outs due to toxicity were SSZ 9, MTX 2, COMBI 5. In conclusion, there were no significant differences in efficacy between combination and single therapy, only a modest trend favouring COMBI. The results of MTX and SSZ were very comparable. Nausea occurred more often in the COMBI group: the number of withdrawals due to adverse events did not differ significantly.
Parenteral high dose methotrexate and sulfasalazine are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.