Combination Of Disease-modifying Antirheumatic Drugs Research Articles

Disease-modifying antirheumatic drugs, including methotrexate, gold, antimalarials, and D-penicillamine.

Recent literature continues to promote the early use of disease-modifying antirheumatic drugs (DMARDs), especially the less toxic agents such as hydroxychloroquine. Reports of combination DMARD treatments have been disappointing, and careful attention must be paid to clinical trial design if the efficacy of combination therapies is to be established. Methotrexate retains its prominent role, and its mechanism of action has been the subject of many reports; its toxicity remains the most common reason for treatment termination. Guidelines for monitoring hepatic toxicity of methotrexate have been published and may help reduce the need for invasive biopsy procedures. Significant risk factors for methotrexate pulmonary toxicity remain difficult to identify. Large placebo-controlled studies of both sulfasalazine and hydroxychloroquine have been reported and have demonstrated the efficacy of these agents in the treatment of early rheumatoid arthritis. Awareness of drug-toxicity profiles is important for physicians who prescribe these agents.

Clinical Trial Design for Evaluating Combination Therapies

Because the differences in efficacy between a disease-modifying antirheumatic drug (DMARD) combination and its constituent drugs are likely to be smaller than those between placebo and the single DMARDs, it has been difficult to prove that any combination of DMARDs has either additive or synergistic benefit. The discriminatory power of the study design can be enhanced by careful attention to the details of patient selection, study design and duration, and choices of primary outcome measures and analytical methods. Use of the American College of Rheumatology (ACR) 'core set' of outcome measures and the proposed ACR 'definition of improvement' for rheumatoid arthritis (RA) clinical trials, with intent-to-treat analysis, in a balanced, prospective, double-blind randomized clinical trial of 1-2 yr duration will optimize the chances of discriminating between the clinical benefit of the combination and its components if a real difference is present.

Overview of Combination Second-Line or Disease-Modifying Antirheumatic Drug Therapy in Rheumatoid Arthritis

This article discusses the use of combinations of disease-modifying antirheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Patients with RA have a disease that can be disabling and life threatening and current therapies do not prevent these complications. The need for more aggressive therapy is apparent. The rationale for combinations of DMARDs is explored and the efficacy and safety of reported combinations is summarized. The variables to be reviewed in selecting a combination of DMARDs are examined. Newer approaches employing multiple DMARDs will be considered.

Bungee jumping and intraocular haemorrhage.

Around 1% of adults in the UK have rheumatoid arthritis (RA).1 UK national guidelines recommend that such people should receive disease-modifying anti-rheumatic drugs (DMARDs) as soon as possible after diagnosis, as earlier treatment is more effective in reducing disease progression.2^,3 Also, it has been proposed that combination DMARD therapy may reduce joint damage more than single drugs.1^,2^,4 In the light of several recently published trials on combination therapy in early RA,5–14 here we update our recommendations on such treatment. 15^,16

Protocol development for combination therapy with disease-modifying antirheumatic drugs

To date, it has been exceptionally difficult to prove that any combination of disease-modifying antirheumatic drugs is more effective than its components used one at a time. However, only a few of many possible combinations have been evaluated in clinical trials. Careful attention to the details of patient selection, study design and duration, and choice of primary outcome measures is essential. A logical strategy for protocol development emphasizes the use of multiple small pilot studies to screen series of combinations and doses to identify a few that appear to show clinical benefit. The most promising combinations can then be evaluated in large, double-blind, randomized, pivotal studies with a higher probability of success.

Therapy for rheumatoid arthritis: Combinations of disease-modifying drugs and new paradigms of treatment

The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The “step-down bridge” strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The “sawtooth” strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a “graduated-step” strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment.

Combination of disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. A survey of Alabama rheumatologists.

Combinations of disease-modifying antirheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) have been recently advocated. Efficacy and toxicity data are scant. We conducted a survey of Alabama rheumatologists to determine actual practice patterns regarding combined DMARD treatment for their patients with RA. No differences were found between academic and nonacademic rheumatologists nor between users and nonusers of combination DMARDs in demographics or practice pattern profiles. The majority did report use of combination DMARD treatment, though only in a small proportion of their patients for whom the pyramid approach had failed. The combination most often employed was gold salts and antimalarials. Users, as compared to nonusers, did favor changing the classic pyramid approach for the treatment of RA, but the differences did not reach statistical significance.

Antimalarial agents compared with or in combination with other disease-modifying antirheumatic drugs

Available published comparisons of antimalarial drugs with other disease-modifying antirheumatic drugs (DMARDs) are reviewed, as well as reports of combinations of DMARDs, in the treatment of rheumatoid arthritis and juvenile rheumatoid arthritis. These reports suggest that antimalarial drug toxicity is less than that of parenteral gold, D-penicillamine, auranofin, or dapsone. Its efficacy appears to be equal to or slightly less than that of most comparison DMARDs. Combinations of DMARDs with antimalarials are probably used by a substantial proportion of rheumatologists, but the few prospective, double-blind studies with a balanced design show little or no advantage to combination DMARD therapy. Open, nonrandomized studies and preliminary reports suggest that combination therapy may be useful, usually when another DMARD is added to one or more DMARDs to which the patients did not have a satisfactory response. A few large, prospective, double-blind, randomized studies comparing hydroxychloroquine with several other DMARDs and placebo are needed to establish more confidence in the relative efficacy and utility of hydroxychloroquine. Although the rationale for combination DMARD therapy is attractive, additional preliminary studies of the various possible combinations and doses are needed before definitive trials of promising combinations can be justified.

Seven cases of cerebromedullospinal disconnection: the "locked-in" syndrome.

Around 1% of adults in the UK have rheumatoid arthritis (RA).1 UK national guidelines recommend that such people should receive disease-modifying anti-rheumatic drugs (DMARDs) as soon as possible after diagnosis, as earlier treatment is more effective in reducing disease progression.2^,3 Also, it has been proposed that combination DMARD therapy may reduce joint damage more than single drugs.1^,2^,4 In the light of several recently published trials on combination therapy in early RA,5–14 here we update our recommendations on such treatment. 15^,16

Preretinal hemorrhages. Their mechanism of production and significance.

<h3>Objectives</h3> To assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response. <h3>Methods</h3> We enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response. <h3>Results</h3> Samples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC. <h3>Conclusions</h3> Patients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.