What are the recent advancements in rheumatology?

Recent Advancements in Rheumatology

The development of biologics and small oral molecules has revolutionized the pharmacologic treatment of systemic rheumatic diseases by targeting specific molecular or cellular pathways directly involved in disease pathogenesis. 1

New Therapeutic Agents and Approaches

Biological Agents

• TNF inhibitors remain cornerstone biologics, including adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab, with proven efficacy in reducing clinical signs of inflammation in patients who have failed conventional DMARDs 1, 2
• Newer biological agents with alternative mechanisms of action have expanded treatment options:
  • IL-6 pathway inhibitors (tocilizumab and sarilumab) have shown effectiveness as both monotherapy and in combination with methotrexate 1, 3
  • T-cell costimulation modulator (abatacept) and anti-CD20 antibody (rituximab) provide options for patients with inadequate response to TNF inhibitors 1, 3
  • IL-17 inhibitors (secukinumab and ixekizumab) have been approved for psoriatic arthritis and axial spondyloarthritis 1
  • IL-12/23 inhibitor (ustekinumab) has shown promise in psoriatic arthritis 1

Small Molecule Inhibitors

• JAK inhibitors represent a major advancement as oral targeted synthetic DMARDs (tsDMARDs) 1
  • Tofacitinib, baricitinib, filgotinib, and upadacitinib have demonstrated efficacy in rheumatoid arthritis 1, 4
  • These agents offer the convenience of oral administration compared to injectable biologics 5
  • Clinical trials have shown JAK inhibitors to be effective in patients with inadequate response to conventional DMARDs or TNF inhibitors 4

Updated Treatment Guidelines and Strategies

Rheumatoid Arthritis

• The 2019 EULAR recommendations emphasize a treat-to-target approach aiming for remission or low disease activity 1
• Initial therapy recommendations include methotrexate (rapidly escalated to 25 mg/week) plus short-term glucocorticoids 1, 6
• For inadequate response to initial therapy within 3-6 months, treatment should be stratified according to risk factors 1
• In patients with poor prognostic factors (autoantibodies, high disease activity, early erosions, or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to csDMARDs 1
• Treatment tapering (but not discontinuation) is recommended for patients in sustained remission 1, 6

Axial Spondyloarthritis

• Updated ASAS-EULAR recommendations now incorporate the entire disease spectrum, including both radiographic and non-radiographic axial spondyloarthritis 1
• Treatment algorithm begins with NSAIDs for 2-4 weeks, followed by consideration of local therapies or biologic therapy if response is inadequate 1
• TNF inhibitors remain first-line biologics, with IL-17 inhibitors as an alternative option 1

Psoriatic Arthritis

• Treatment guidelines from GRAPPA, EULAR, and ACR/NPF have been updated to incorporate new therapies and address comorbidities 1
• Treatment algorithm includes NSAIDs and local glucocorticoid injections initially, followed by conventional DMARDs, and then biologics or small molecules for active disease 1
• Treatment selection should consider specific disease manifestations (peripheral arthritis, axial disease, enthesitis, dactylitis, skin involvement) 1

Biomarker-Guided Treatment Selection

• Presence of rheumatoid factor, anti-citrullinated protein antibodies, or elevated serum IgG may predict better response to rituximab 3
• Seronegative patients may respond better to abatacept or tocilizumab 3
• Research continues to identify reliable biomarkers for diagnosing rheumatic diseases and predicting treatment response 1

Biosimilars and Cost Considerations

• The availability of biosimilars offers the opportunity to reduce treatment costs while maintaining efficacy 1
• Economic considerations are increasingly important in treatment decisions, with recommendations that the least expensive bDMARD should be used in treatment-naïve patients 1
• Scientific societies have started developing position papers on how to use biosimilars appropriately 1

Personalized Medicine Approaches

• Despite advances, reliable biomarkers for personalizing treatment remain limited 1
• The multibiomarker disease activity panel (MBDA/VectraDA) has been approved by the FDA for assessing RA disease activity, though its clinical utility remains debated 1
• Treatment decisions increasingly consider comorbidities, with specific guidelines developed for managing RA patients with diabetes, inflammatory bowel disease, and high infection risk 1

Common Pitfalls to Avoid

• Delaying DMARD initiation after diagnosis can lead to irreversible joint damage 3, 6
• Inadequate methotrexate dosing or insufficient duration of treatment trial before concluding treatment failure 3, 6
• Long-term glucocorticoid use without appropriate monitoring for adverse effects 3, 6
• Failure to adjust therapy when treatment targets are not met within the recommended timeframes (improvement by 3 months, target by 6 months) 1, 6
• Overlooking comorbidities that may influence treatment selection, such as hepatitis, tuberculosis, or heart failure 1, 3

The field of rheumatology continues to evolve rapidly with new targeted therapies and treatment strategies focused on achieving remission or low disease activity, preventing structural damage, and improving patients' quality of life.