Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis

A preventive strategy

Theodore Pincus, James Robert O'Dell, Joel M. Kremer

Research output: Contribution to journalReview article

124 Citations (Scopus)

Abstract

The traditional 'pyramid' or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti- inflammatory drug for months to years while seeking to avoid use of second- line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a 'preventive' strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used 'anchor drug' in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.

Original languageEnglish (US)
Pages (from-to)768-774
Number of pages7
JournalAnnals of internal medicine
Volume131
Issue number10
DOIs
StatePublished - Nov 16 1999

Fingerprint

Antirheumatic Agents
Rheumatoid Arthritis
Joints
leflunomide
Methotrexate
Hydroxychloroquine
Inflammation
Sulfasalazine
Premature Mortality
Drug Combinations
Therapeutics
Combination Drug Therapy
Cyclosporine
Observational Studies
Patient Care
Anti-Inflammatory Agents
Randomized Controlled Trials
Economics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis : A preventive strategy. / Pincus, Theodore; O'Dell, James Robert; Kremer, Joel M.

In: Annals of internal medicine, Vol. 131, No. 10, 16.11.1999, p. 768-774.

Research output: Contribution to journalReview article

@article{c1ee900a8b394c9fb29f56192c7b92c2,
title = "Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: A preventive strategy",
abstract = "The traditional 'pyramid' or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti- inflammatory drug for months to years while seeking to avoid use of second- line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a 'preventive' strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used 'anchor drug' in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.",
author = "Theodore Pincus and O'Dell, {James Robert} and Kremer, {Joel M.}",
year = "1999",
month = "11",
day = "16",
doi = "10.7326/0003-4819-131-10-199911160-00009",
language = "English (US)",
volume = "131",
pages = "768--774",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "10",

}

TY - JOUR

T1 - Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis

T2 - A preventive strategy

AU - Pincus, Theodore

AU - O'Dell, James Robert

AU - Kremer, Joel M.

PY - 1999/11/16

Y1 - 1999/11/16

N2 - The traditional 'pyramid' or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti- inflammatory drug for months to years while seeking to avoid use of second- line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a 'preventive' strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used 'anchor drug' in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.

AB - The traditional 'pyramid' or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti- inflammatory drug for months to years while seeking to avoid use of second- line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a 'preventive' strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used 'anchor drug' in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.

UR - http://www.scopus.com/inward/record.url?scp=0032760136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032760136&partnerID=8YFLogxK

U2 - 10.7326/0003-4819-131-10-199911160-00009

DO - 10.7326/0003-4819-131-10-199911160-00009

M3 - Review article

VL - 131

SP - 768

EP - 774

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 10

ER -