The Role of NSAIDs in Managing Inflammatory Conditions

body with joints highlighted

The Role of NSAIDs in Managing Inflammatory Conditions

Viral Patel
Viral Patel

Galt Pharmaceuticals Medical Affairs Fellow, 2024-2025

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medication used to treat various inflammatory conditions due to their analgesic, antipyretic, and anti-inflammatory properties. NSAIDs main mechanism of action is the inhibition of the enzyme cyclooxygenase (COX). This enzyme is crucial for the synthesis of prostaglandins which are involved in various inflammatory processes.1

Key inflammatory conditions treated with NSAIDs include:

  1. Rheumatoid Arthritis (RA)
    1. Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. It is a chronic inflammatory disorder caused in many cases by the interaction between genes and environmental factors.2
    2. NSAIDs are commonly used to manage pain and inflammation in RA. They provide symptomatic relief but do not alter the disease course.3
  1. Osteoarthritis (OA)
    1. Osteoarthritis is the most common form of arthritis in the world. OA is degenerative joint disease characterized by the breakdown of cartilage and the underlying bone, causing pain, stiffness, and limited movement.4
    2. NSAIDs are effective in reducing pain and improving function in patients with OA.
  1. Acute gout
    1. Gout is one of the most common causes of chronic inflammatory arthritis in the United States. Gout is characterized by monohydrate crystals deposited in tissue.5
    2. NSAIDs are first-line treatment for acute gout flares, providing significant pain relief and reduction in inflammation in affected joints.6
  1. Ankylosing Spondylitis (AS)
    1. Ankylosing spondylitis is a chronic, inflammatory disease of the axial spine. Chronic back pain and progressive spinal stiffness are the most common features of this disease.7
    2. NSAIDs are recommended as first-line therapy for reducing pain and stiffness in AS. Continuous NSAID treatment is often advised for persistently active disease per the American College of Rheumatology.8
  1. Primary dysmenorrhea
    1. Primary dysmenorrhea is defined as cramping pain in the lower abdomen occurring just before or during menstruation, in the absence of other diseases.9
    2. NSAIDs have been shown to be effective agents in managing pain associated with primary dysmenorrhea.10

The dosage and duration of NSAID therapy should be tailored to the individual patient’s needs, balancing efficacy with the risk of adverse effects, particularly gastrointestinal, renal and cardiovascular complications.

References

  1. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547742/
  2. Chauhan K, Jandu JS, Brent LH, et al. Rheumatoid Arthritis. [Updated 2023 May 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441999/
  3. Braun J, Baraliakos X, Westhoff T. Nonsteroidal anti-inflammatory drugs and cardiovascular risk – a matter of indication. Semin Arthritis Rheum. 2020;50(2):285-288. doi:10.1016/j.semarthrit.2019.07.012
  4. Sen R, Hurley JA. Osteoarthritis. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482326/
  5. Fenando A, Rednam M, Gujarathi R, et al. Gout. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546606/
  6. van Durme CM, Wechalekar MD, Landewé RB, et al. Non-steroidal anti-inflammatory drugs for acute gout. Cochrane Database Syst Rev. 2021;12(12):CD010120. Published 2021 Dec 9. doi:10.1002/14651858.CD010120.pub3
  7. Wenker KJ, Quint JM. Ankylosing Spondylitis. [Updated 2023 Jun 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470173/
  8. Poddubnyy D, van der Heijde D. Therapeutic controversies in spondyloarthritis: nonsteroidal anti-inflammatory drugs. Rheum Dis Clin North Am. 2012;38(3):601-611. doi:10.1016/j.rdc.2012.08.005
  9. Coco AS. Primary dysmenorrhea. Am Fam Physician. 1999;60(2):489-496.
  10. Itani R, Soubra L, Karout S, Rahme D, Karout L, Khojah HMJ. Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates. Korean J Fam Med. 2022;43(2):101-108. doi:10.4082/kjfm.21.0103

The information provided is for general informational and educational purposes only. It is not intended to serve as medical advice, diagnosis, or treatment. The content is written by a licensed pharmacist and reflects general knowledge and expertise in the healthcare field, but it is not a substitute for professional medical advice from a qualified healthcare provider.

Always consult your physician, pharmacist, or other qualified healthcare professional before starting, stopping, or modifying any medication, treatment, or health regimen. Individual health conditions and needs vary, and only a healthcare professional can provide personalized advice tailored to your specific situation.

While we strive to ensure the accuracy and currency of the information presented, medical knowledge is constantly evolving, and errors or omissions may occur. The blog’s content does not cover all possible uses, precautions, side effects, or interactions of medications or treatments. Reliance on any information provided is solely at your own risk.

Links to external websites or resources are provided for convenience and do not imply endorsement or responsibility for their content.

Managing Breakthrough Pain in Rheumatoid Arthritis

Managing Breakthrough Pain in Rheumatoid Arthritis

Scott Chappell
Scott Chappell

Galt Pharmaceuticals Director of Medical Affairs

Adjusting current DMARD (Disease Modifying Antirheumatic Drugs) therapy, utilizing non-pharmacologic therapies and employing NSAIDs play significant roles in managing breakthrough symptoms for rheumatoid arthritis (RA) management.

Managing Breakthrough Pain with Current DMARD Therapy

Managing of breakthrough symptoms with current DMARD therapy, the treatment options are guided by the 2021 American College of Rheumatology (ACR) guidelines.[1]

  1. Optimization of Current DMARD Therapy: If a patient is experiencing breakthrough symptoms, the first step is to optimize the current disease-modifying antirheumatic drug (DMARD) regimen. This may involve increasing the dose of the current DMARD or adding another conventional synthetic DMARD (csDMARD) such as methotrexate, hydroxychloroquine, sulfasalazine, or leflunomide.[1]

  2. Switching or Adding Biologic DMARDs (bDMARDs): If optimization of csDMARDs is insufficient, the next step is to consider biologic DMARDs. Options include TNF inhibitors (e.g., etanercept, adalimumab, infliximab), IL-6 receptor inhibitors (e.g., tocilizumab, sarilumab), T cell costimulatory inhibitors (e.g., abatacept), and B cell depleting agents (e.g., rituximab). [1-2]

  3. Targeted Synthetic DMARDs (tsDMARDs): For patients who do not respond adequately to bDMARDs, targeted synthetic DMARDs such as Janus kinase (JAK) inhibitors (e.g., tofacitinib, baricitinib, Upadacitinib) can be considered.[1]

  4. Switching Mechanisms of Action: If a patient fails to respond to one class of bDMARDs, switching to a different mechanism of action (e.g., from a TNF inhibitor to an IL-6 receptor inhibitor or a JAK inhibitor) is recommended. [3-4]

  5. Combination Therapy: Combining csDMARDs with bDMARDs or tsDMARDs can be effective in managing breakthrough symptoms and achieving better disease control. [1-2]

  6. Glucocorticoids: Short-term use of glucocorticoids can be considered for rapid symptom relief, but long-term use is generally discouraged due to potential adverse effects.[1][5]

These strategies should be tailored to the individual patient, considering factors such as disease severity, comorbidities, and previous treatment responses. Regular monitoring and a treat-to-target approach are essential to optimize outcomes.[1][6]

Non-Pharmacologic Interventions for Breakthrough Pain

The 2022 American College of Rheumatology (ACR) guidelines recommend several non-pharmacologic interventions for RA management. [7] 

  1. Exercise Therapy: Regular aerobic and strength exercises improve physical function and reduce pain.

  2. Therapeutic Patient Education: Educating patients on self-management strategies, including joint protection and energy conservation, is beneficial.

  3. Physical and Occupational Therapy: Tailored exercise programs, assistive devices, and ergonomic advice help maintain joint function and reduce pain.

  4. Orthoses and Assistive Devices: Devices like wrist splints and foot orthoses provide joint support and pain relief.

  5. Dietary Interventions: Diets such as the Mediterranean diet, which emphasizes vegetables, fruits, whole grains, and healthy fats, may have anti-inflammatory effects.

  6. Cognitive Behavioral Therapy (CBT): CBT helps manage the psychological impact of RA, improving overall quality of life.

  7. Balneotherapy: Mineral baths can provide symptomatic relief.

  8. Mind-Body Approaches: Techniques like mindfulness, meditation, and biofeedback can help manage pain and stress.

NSAIDs for Breakthrough Pain

NSAIDs are effective for managing breakthrough pain in RA by reducing inflammation and pain. However, NSAIDs should be used at the lowest effective dose for the shortest duration to minimize risks such as gastrointestinal complications and cardiovascular events.[3]

In summary, adjusting DMARD therapy, utilizing non-pharmacologic therapies, and employing NSAIDs for the proper patient can effectively manage breakthrough symptoms in RA, enhancing patient outcomes and quality of life.

References:

  1. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Fraenkel L, Bathon JM, England BR, et al. Arthritis Care & Research. 2021;73(7):924-939. doi:10.1002/acr.24596.
  2. Optimizing Outcomes in Rheumatoid Arthritis Patients With Inadequate Responses to Disease-Modifying Anti-Rheumatic Drugs. Pavelka K, Kavanaugh AF, Rubbert-Roth A, Ferraccioli G. Rheumatology (Oxford, England). 2012;51 Suppl 5:v12-21. doi:10.1093/rheumatology/kes111.
  3. The Management of First-Line Biologic Therapy Failures in Rheumatoid Arthritis: Current Practice and Future Perspectives. Favalli EG, Raimondo MG, Becciolini A, et al. Autoimmunity Reviews. 2017;16(12):1185-1195. doi:10.1016/j.autrev.2017.10.002.
  4. Optimizing Outcomes in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-TNF Treatment. Emery P. Rheumatology (Oxford, England). 2012;51 Suppl 5:v22-30. doi:10.1093/rheumatology/kes115.
  5. Strategies Toward Rheumatoid Arthritis Therapy; The Old and the New. Abbasi M, Mousavi MJ, Jamalzehi S, et al. Journal of Cellular Physiology. 2019;234(7):10018-10031. doi:10.1002/jcp.27860.
  6. Treating to Target in Established Rheumatoid Arthritis: Challenges and Opportunities in an Era of Novel Targeted Therapies and Biosimilars. Woodworth TG, den Broeder AA. Best Practice & Research. Clinical Rheumatology. 2015 Aug-Dec;29(4-5):543-9. doi:10.1016/j.berh.2015.10.001.
  7. 2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis. England BR, Smith BJ, Baker NA, et al. Arthritis & Rheumatology (Hoboken, N.J.). 2023;75(8):1299 1311doi:10.1002/art.42507.

The information provided is for general informational and educational purposes only. It is not intended to serve as medical advice, diagnosis, or treatment. The content is written by a licensed pharmacist and reflects general knowledge and expertise in the healthcare field, but it is not a substitute for professional medical advice from a qualified healthcare provider.

Always consult your physician, pharmacist, or other qualified healthcare professional before starting, stopping, or modifying any medication, treatment, or health regimen. Individual health conditions and needs vary, and only a healthcare professional can provide personalized advice tailored to your specific situation.

While we strive to ensure the accuracy and currency of the information presented, medical knowledge is constantly evolving, and errors or omissions may occur. The blog’s content does not cover all possible uses, precautions, side effects, or interactions of medications or treatments. Reliance on any information provided is solely at your own risk.

Links to external websites or resources are provided for convenience and do not imply endorsement or responsibility for their content.

 

 

 

 

Brief History and Proper Utilization of NSAIDs

Brief History and Proper Utilization of Nonsteroidal Anti-inflammatory Drugs

Scott Chappell
Scott Chappell

Galt Pharmaceuticals Director of Medical Affairs

Background on NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have a long and storied history, beginning with the use of salicylate-containing willow bark for pain and fever relief in ancient cultures. The active component, salicylic acid, was chemically synthesized in 1860, leading to the development of acetylsalicylic acid (aspirin) in 1897. Aspirin’s success spurred the development of other NSAIDs, which were initially organic acids but later included non-acidic compounds.

NSAIDs exert their effects primarily through the inhibition of cyclooxygenase (COX) enzymes, which are crucial for prostaglandin synthesis. There are two main isoforms: COX-1, which is involved in maintaining physiological functions such as gastrointestinal protection and platelet aggregation, and COX-2, which is induced during inflammation and mediates pain and fever. The discovery of these isoforms in the 1990s led to the development of selective COX-2 inhibitors (coxibs), designed to reduce gastrointestinal side effects associated with non-selective NSAIDs. However, the introduction of coxibs like celecoxib and rofecoxib revealed significant cardiovascular risks, leading to the withdrawal of rofecoxib from the market in 2004. This highlighted the need for a balance between efficacy and safety in NSAID therapy.

NSAIDs have widespread use and therapeutic benefits, but note that they are associated with adverse effects, including gastrointestinal ulcers, cardiovascular events, and renal toxicity. Strategies to mitigate these risks include using the lowest effective dose for the shortest duration and co-prescribing gastroprotective agents like proton-pump inhibitors for high-risk patients. The ongoing evolution of NSAIDs aims to enhance their safety while maintaining their efficacy in treating pain, inflammation, and fever.

Mitigating the Risks for Patients Who Need to use NSAIDs

To monitor and mitigate the risks for patients who need to use NSAIDs, especially those with a history of gastrointestinal (GI) bleeding, cardiovascular disease, or renal impairment, several strategies can be employed:

  1. Use the Lowest Effective Dose for the Shortest Duration: This is a fundamental principle to minimize adverse effects. The FDA emphasizes this approach to reduce the risk of GI bleeding, cardiovascular events, and renal toxicity.
  2. Gastrointestinal Protection: For patients with a history of GI bleeding or at high risk, co-therapy with proton-pump inhibitors (PPIs) or misoprostol is recommended. The American College of Gastroenterology advises using a COX-2 inhibitor plus a PPI or misoprostol for high-risk patients. Testing and eradicating  pyloriinfection can also reduce the risk of peptic ulcers in NSAID users.
  3. Cardiovascular Risk Management: The American Heart Association recommends avoiding NSAIDs, particularly COX-2 inhibitors, in patients with cardiovascular disease. If NSAIDs are necessary, naproxen may be preferred due to its relatively lower cardiovascular risk. Monitoring blood pressure and managing other cardiovascular risk factors are crucial.
  4. Renal Function Monitoring: Regular monitoring of renal function, fluid retention, and electrolyte levels is essential, especially in patients with preexisting renal impairment, heart failure, or those on diuretics or ACE inhibitors. The FDA and other literature recommend avoiding NSAIDs in patients with advanced renal disease and using alternative therapies when possible.
  5. Patient Education and Monitoring: Educate patients about the signs and symptoms of GI bleeding, cardiovascular events, and renal impairment. Regular follow-up and prompt evaluation of any adverse symptoms are critical.

By implementing these strategies, clinicians can better manage the risks associated with NSAIDs used in vulnerable patient populations.

Patient Groups That Should Avoid NSAIDs

Certain patient groups should avoid using nonsteroidal anti-inflammatory drugs (NSAIDs) due to their potential adverse effects, including gastrointestinal (GI) ulcers, cardiovascular events, and renal toxicity.

  • Elderly patients are at increased risk for NSAID-related adverse effects, including GI bleeding, renal impairment, and cardiovascular events. Elderly patients, especially those with comorbidities, are particularly vulnerable to these risks.
  • Patients with a history of peptic ulcer disease or gastrointestinal bleeding should avoid NSAIDs due to a significantly increased risk of GI bleeding. The FDA notes that these patients have a greater than 10-fold increased risk for developing a GI bleed when using NSAIDs.
  • Patients with cardiovascular disease or patients at high risk for cardiovascular events should avoid NSAIDs, particularly COX-2 inhibitors, due to the increased risk of myocardial infarction and stroke. The American Heart Association advises against the use of NSAIDs in patients with established cardiovascular disease.
  • Patients with renal impairment, heart failure, or chronic kidney disease (CKD) should avoid NSAIDs due to the risk of worsening renal function and potential for acute kidney injury. The National Comprehensive Cancer Network (NCCN) guidelines recommend caution in these patients to prevent renal toxicities.
  • Patients on concurrent anticoagulant or corticosteroid therapy should avoid NSAIDs due to the increased risk of GI bleeding and other complications. The NCCN guidelines also emphasize the increased bleeding risk when NSAIDs are used with anticoagulants.

List of NSAIDs Available in the United States

The following is a list of commonly available NSAIDs in the United States by generic and brand name:

Ibuprofen (Advil®, Motrin®, IBU®)

Naproxen (Aleve®, Naprosyn®, Naprelan®)

Diclofenac (Voltaren®, Cataflam®)

Celecoxib (Celebrex®)

Meloxicam (Mobic®)

Indomethacin (Indocin®)

Ketorolac (Toradol®)

Etodolac (Lodine®)

Piroxicam (Feldene®)

Sulindac (Clinoril®)

Diflunisal (Dolobid®)

Salsalate (Disalcid®)

Oxaprozin (Daypro®)

Nabumetone (Relafen®)

Flurbiprofen (Ansaid®)

Fenoprofen (Nalfon®)

Meclofenamate (Meclomen®)

Tolmetin (Tolectin®DS)

NSAIDs are commonly used to treat a range of conditions, from minor aches and pains to chronic diseases such as arthritis. As a result, NSAIDs are highly effective for conditions like headaches, menstrual cramps, sprains, and inflammatory disorders such as osteoarthritis and rheumatoid arthritis.

NSAIDs are highly beneficial for managing pain and inflammation, but like all medications, they should be used with care, balancing their effectiveness against potential side effects.

References

  1. Vane JR, Botting RM. Mechanism of Action of Nonsteroidal Anti-Inflammatory Drugs. The American Journal of Medicine. 1998;104(3A):2S-8S; discussion 21S-22S.K. D.
  2. Rainsford, “ANTI-INFLAMMATORY DRUGS IN THE 21ST CENTURY,” Sub-Cellular Biochemistry. 2007;42:3-27
  3. Vonkeman HE, van de Laar MA. “Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention,” Seminars in Arthritis and /Rehumatism. 2010;39(4):294-312.
  4. Wehling M., Non-Steroidal Anti-Inflammatory Drug Use in Chronic Pain Conditions With Special Emphasis on the Elderly and Patients With Relevant Comorbidities: Management and Mitigation of Risks and Adverse Effects. European Journal of Clinical Pharmacology. 2014;70(10):1159-72.
  5. Antman EM, Bennett JS, Daugherty A, et al. Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association. Circulation. 2007;115(12):1634-42.
  6. Bouck Z, Mecredy GC, Ivers NM, et al. Frequency and Associations of Prescription Nonsteroidal Anti-Inflammatory Drug Use Among Patients With a Musculoskeletal Disorder and Hypertension, Heart Failure, or Chronic Kidney Disease. JAMA Internal Medicine. 2018;178(11):1516-1525. doi:10.1001/jamainternmed.2018.4273.
  7. Lanza FL, Chan FK, Quigley EM. Guidelines for Prevention of NSAID-related Ulcer Complications. The American Journal of Gastroenterology. 2009;104(3):728-38.
  8. Wilcox CM, Allison J, Benzuly K, et al. Consensus Development Conference on the Use of Nonsteroidal Anti-Inflammatory Agents, Including Cyclooxygenase-2 Enzyme Inhibitors and Aspirin. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association. 2006;4(9):1082-9.
  9. Domper Arnal MJ, Hijos-Mallada G, Lanas A. Gastrointestinal and Cardiovascular Adverse Events Associated With NSAIDs. Expert Opinion on Drug Safety. 2022;21(3):373-384.
  10. Ković SV, Vujović KS, Srebro D, Medić B, Ilic-Mostic T. Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs. Current Medicinal Chemistry. 2016;23(19):1953-64. 
  11. LaForge JM, Urso K, Day JM, et al. Non-Steroidal Anti-Inflammatory Drugs: Clinical Implications, Renal Impairment Risks, and AKI. Advances in Therapy. 2023;40(5):2082-2096.
  12. Ribeiro H, Rodrigues I, Napoleão L, et al. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Pain and Aging: Adjusting Prescription to Patient Features. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2022;150:112958.
  13. Domper Arnal MJ, Hijos-Mallada G, Lanas A. Gastrointestinal and Cardiovascular Adverse Events Associated With NSAIDs. Expert Opinion on Drug Safety. 2022;21(3):373-384.
  14. Nam YH, Brensinger CM, Bilker WB, et al. Nonsteroidal Anti-Inflammatory Drug Choice and Adverse Outcomes in Clopidogrel Users: A Retrospective Cohort Study. PloS One. 2018;13(3):e0193800. doi:10.1371/journal.pone.0193800.

The information provided is for general informational and educational purposes only. It is not intended to serve as medical advice, diagnosis, or treatment. The content is written by a licensed pharmacist and reflects general knowledge and expertise in the healthcare field, but it is not a substitute for professional medical advice from a qualified healthcare provider.

Always consult your physician, pharmacist, or other qualified healthcare professional before starting, stopping, or modifying any medication, treatment, or health regimen. Individual health conditions and needs vary, and only a healthcare professional can provide personalized advice tailored to your specific situation.

While we strive to ensure the accuracy and currency of the information presented, medical knowledge is constantly evolving, and errors or omissions may occur. The blog’s content does not cover all possible uses, precautions, side effects, or interactions of medications or treatments. Reliance on any information provided is solely at your own risk.

Links to external websites or resources are provided for convenience and do not imply endorsement or responsibility for their content.