Drug resistance in rheumatological diseases

Hassan Waqar, Ammar Arshad, Muhammad Asad Raza, Mohammad Qamar Nasir, Ahmed Shams Nasir, Arshad Islam, Ifra Idrees, Sarfraz Ahmed, Khalid Muhammad, Atif Amin Baig

Research output: Chapter in Book/Report/Conference proceedingChapter


Rheumatological diseases are chronic inflammatory diseases that involve joints, skin, vessels, and other organ systems. Steroids, DMARDS, and various biological agents are used to control the disease activity by interfering at various levels of the inflammatory cascade. Long term use of the above-mentioned agents is required for treatment, which leads to resistance against these agents. Drug resistance involves various mechanisms that are not completely understood. Proposed mechanisms involve drug uptake and drug efflux transporters, e.g., P-glycoprotein, multidrug resistance protein-1, and organ anion transporters-3, Antidrug antibodies against various anti-TNF drugs, down regulation of Receptors, reprogramming of stimulatory signals, and genetic polymorphisms. Drug resistance is also complicated by non-compliance and the emergence of drug-related adverse effects. Different strategies are proposed to overcome drug resistance that includes the use of a combination of drugs that increase the intracellular concentration of drugs as well as bypass or suppress the multidrug resistance. Alternative agents with slightly different mechanisms of action but similar end targets can also be prescribed. Modification of intracellular signal transduction is also one way to overcome resistance. However, further studies are required to get more insight into the mechanisms of resistance. This will pave new ways to overcome drug resistance, helping in more effective control of disease progression. In this chapter, we will be giving an overview of major rheumatologic diseases, followed by the major drugs used to treat them, the mechanisms of action and mechanisms of resistance to these drugs, and the proposed evidence-based steps to overcome that resistance.

Original languageEnglish
Title of host publicationBiochemistry of Drug Resistance
PublisherSpringer International Publishing
Number of pages14
ISBN (Electronic)9783030763206
ISBN (Print)9783030763190
Publication statusPublished - Aug 5 2021

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Health Professions
  • General Medicine


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