What can you take long term instead of prednisone?

October 6, 2025 •

4 min read

Studies suggest that between 12.2% and 18.1% of people who receive oral glucocorticoids like prednisone become long-term users [1.5.2]. For these individuals, the critical question becomes: what can you take long term instead of prednisone?

Quick Summary

Managing chronic inflammation often requires moving beyond prednisone. This overview details safer, long-term alternatives, including DMARDs, biologics, and other immunosuppressants.

Key Points

Why Avoid Long-Term Prednisone: Significant side effects like bone loss, weight gain, high blood sugar, and increased infection risk drive the need for alternatives [1.4.1, 1.4.4].
Conventional DMARDs as a Foundation: Medications like methotrexate are often a first-line, long-term treatment that broadly suppress the immune system to control disease [1.6.4, 1.7.4].
Biologics Offer Targeted Therapy: Newer biologic drugs (e.g., Humira, Enbrel) are engineered to block specific inflammatory proteins like TNF-alpha, offering a more precise approach [1.7.1].
JAK Inhibitors are Oral Innovations: This newer class of drugs, such as Xeljanz, works inside immune cells to block inflammation signals and are taken as pills [1.8.1, 1.8.3].
Decision is Highly Individual: The choice of a prednisone alternative depends on the specific condition, severity, and a detailed risk-benefit analysis with a doctor [1.3.1].
Never Stop Steroids Abruptly: Abruptly discontinuing prednisone can cause a steroid withdrawal syndrome and is dangerous; tapering must be medically supervised [1.3.2].
Lifestyle Plays a Supporting Role: An anti-inflammatory diet, stress management, and moderate exercise can help manage inflammation but do not replace prescribed medications [1.2.4, 1.11.4].

Prednisone is a powerful corticosteroid that can be life-saving for managing acute inflammation in a wide range of autoimmune and inflammatory conditions [1.4.1]. However, its benefits can be overshadowed by a host of serious side effects when used long term [1.4.2]. This reality pushes patients and doctors to seek more sustainable options for managing chronic disease. Fortunately, a robust field of pharmacology known as 'steroid-sparing' therapy offers many effective alternatives [1.3.1].

Why Seek Long-Term Alternatives to Prednisone?

Long-term use of oral corticosteroids is associated with a wide range of significant side effects. These risks are the primary driver for finding alternative treatments [1.4.2].

Key risks of prolonged prednisone use include:

Bone Thinning (Osteoporosis): Steroids can lead to a loss of bone density, increasing fracture risk. Some patients may lose 10-20% of their bone mass within the first six months of treatment [1.4.4, 1.4.5].
Metabolic Changes: Increased appetite, weight gain (especially in the abdomen), fluid retention, high blood pressure, and elevated blood sugar levels are common. Long-term use can even lead to diabetes [1.4.1, 1.4.2, 1.4.4].
Increased Infection Risk: Prednisone suppresses the immune system, making individuals more vulnerable to infections [1.4.2, 1.4.4].
Mood and Sleep Disturbances: Side effects can include mood swings, anxiety, depression, and insomnia [1.4.1, 1.4.3, 1.4.5].
Eye Problems: Long-term use can increase the risk of developing cataracts or glaucoma [1.4.1, 1.4.2].
Skin Changes: Thinning skin, acne, and reddish-purple stretch marks can occur [1.4.3].

Major Classes of Prednisone Alternatives (Steroid-Sparing Agents)

Steroid-sparing agents are medications that help reduce the need for corticosteroids, thereby minimizing the side effects associated with long-term steroid use [1.3.1]. They are generally grouped into several classes.

Conventional Synthetic DMARDs (csDMARDs)

These are often the first-line long-term treatments for many autoimmune conditions. They work by broadly suppressing the overactive immune system and take weeks to months to become fully effective [1.6.3, 1.6.4].

Methotrexate: Considered a cornerstone treatment for conditions like rheumatoid arthritis, it works by inhibiting enzymes essential for immune cell replication [1.6.4, 1.7.4]. It is often taken once weekly [1.3.3].
Leflunomide (Arava): This drug stops immune cells from multiplying [1.6.3].
Hydroxychloroquine (Plaquenil): Used for milder autoimmune conditions like lupus and rheumatoid arthritis, it works by inhibiting immune response and suppressing inflammation [1.2.4, 1.6.3].
Sulfasalazine: This medication helps protect tissues from the damage caused by inflammation [1.6.3].

Biologic Agents (bDMARDs)

Biologics are a newer, more advanced class of drugs derived from living cells. Unlike csDMARDs that have a broad effect, biologics are genetically engineered to target very specific parts of the immune system involved in the inflammatory process [1.6.4, 1.7.1]. They are typically administered via injection or infusion [1.2.5].

TNF-alpha Inhibitors: This is the most common class of biologics. They block a protein called Tumor Necrosis Factor-alpha (TNF-alpha), a major driver of inflammation [1.7.1, 1.7.3]. Examples include Adalimumab (Humira), Etanercept (Enbrel), and Infliximab (Remicade) [1.2.4, 1.7.1].
Interleukin (IL) Inhibitors: These drugs target various interleukin proteins (like IL-1, IL-6, IL-17, or IL-23) that signal and promote inflammation [1.7.1, 1.7.2]. Examples include Tocilizumab (Actemra) and Secukinumab (Cosentyx) [1.6.3, 1.7.2].
B-cell and T-cell Inhibitors: These agents target specific white blood cells (B-lymphocytes or T-lymphocytes) to reduce the autoimmune response [1.7.1]. Examples include Rituximab (Rituxan) and Abatacept (Orencia) [1.7.1].

Targeted Synthetic DMARDs (tsDMARDs) - JAK Inhibitors

Janus Kinase (JAK) inhibitors are a new class of small-molecule drugs taken orally. They work from inside immune cells to disrupt the signaling pathways that trigger inflammation [1.6.3, 1.8.3].

Examples include Tofacitinib (Xeljanz), Baricitinib (Olumiant), and Upadacitinib (Rinvoq) [1.8.1, 1.8.2].

Other Immunosuppressants

These drugs are also used to suppress the immune system and are often employed in organ transplantation and severe autoimmune diseases [1.10.1, 1.10.2].

Azathioprine: A purine analog that inhibits cell proliferation [1.3.2].
Mycophenolate Mofetil (Cellcept): Inhibits an enzyme crucial for the proliferation of B-cells and T-cells [1.3.2, 1.10.2].
Cyclosporine and Tacrolimus: These are calcineurin inhibitors that block T-cell activation [1.3.2].

Comparison of Common Prednisone Alternatives

Choosing an alternative involves weighing factors like the specific condition being treated, efficacy, side effect profile, cost, and method of administration.


Feature	Methotrexate (csDMARD)	Adalimumab (Humira, a bDMARD)
Mechanism	Broadly inhibits enzymes for immune cell replication [1.6.4].	Specifically blocks TNF-alpha, a key inflammation protein [1.7.1].
Administration	Oral tablet or subcutaneous injection, typically once weekly [1.3.3, 1.9.2].	Subcutaneous injection, typically every 2 weeks [1.3.3, 1.9.2].
Onset of Action	Slower; may take several weeks to months for full effect [1.6.3].	Faster; clinical response can be seen more rapidly than with methotrexate [1.9.1].
Common Side Effects	Nausea, fatigue, hair loss, mouth sores, liver enzyme elevation [1.9.2]. Requires folic acid supplementation [1.3.3].	Injection site reactions, increased risk of infections (especially upper respiratory), headache [1.9.2].
Monitoring	Regular blood tests for liver function and blood counts are essential [1.3.2].	Screening for tuberculosis is required before starting. Monitoring for signs of infection is crucial [1.3.3].

The Role of Lifestyle and Complementary Therapies

While no natural remedy can replace the potent effect of prescription medications for serious autoimmune disease, certain lifestyle choices and supplements may help manage inflammation and support overall health [1.11.4].

Anti-Inflammatory Diet: Emphasizing foods rich in omega-3 fatty acids (like salmon), antioxidants (berries, spinach), and spices like turmeric may help reduce inflammation naturally [1.2.4, 1.11.4].
Supplements: Some studies suggest potential anti-inflammatory benefits from supplements like fish oil (Omega-3s), turmeric (curcumin), and Vitamin D, though their effects are subtle and they should not replace medical treatment [1.11.2, 1.11.3].
Stress Management & Exercise: Chronic stress can worsen inflammation. Techniques like yoga and meditation, along with moderate exercise (about 20-30 minutes daily), can help lower the body's inflammatory response [1.2.4, 1.11.4].

Conclusion: Partnering with Your Doctor

Moving away from long-term prednisone use is a common goal for many patients with chronic inflammatory diseases. A wide array of steroid-sparing alternatives—from traditional DMARDs like methotrexate to highly targeted biologics and JAK inhibitors—now exists. The best choice is highly individual and depends on the specific disease, its severity, your medical history, and a thorough discussion of risks and benefits with your healthcare provider. Never attempt to stop or change your prednisone dosage without direct medical supervision, as abrupt discontinuation can be dangerous [1.3.2].

For more information on one of the most common classes of alternatives, you can visit the Arthritis Foundation's page on Biologics.

Frequently Asked Questions

There is no single 'safest' alternative for everyone. The choice depends on the specific autoimmune disease, patient's health profile, and tolerance. Options range from conventional DMARDs like hydroxychloroquine and methotrexate to biologics, each with its own safety profile that must be discussed with a doctor [1.2.4, 1.3.1].

No. Abruptly stopping prednisone can lead to steroid withdrawal syndrome, which can be dangerous. A doctor must supervise a gradual tapering of the dose to allow your body to adjust [1.3.2].

It varies by drug class. Conventional DMARDs like methotrexate can take several weeks or even months to reach their full effect [1.6.3]. Biologics and JAK inhibitors often work more quickly, sometimes showing results in a few weeks [1.9.1].

Biologics are often more targeted and can be more effective, especially for patients who don't respond to conventional DMARDs [1.9.1]. However, they are also more expensive and carry their own risks, such as an increased chance of infection, so the 'better' option is highly individualized [1.2.5, 1.7.1].

No proven natural remedies can replace prednisone for managing serious inflammatory conditions [1.2.4]. However, an anti-inflammatory diet, supplements like turmeric and fish oil, and stress management can play a supportive role in reducing overall inflammation [1.11.3, 1.11.4].

Steroid-sparing agents are medications used to reduce or eliminate the need for long-term corticosteroid (prednisone) use. This category includes DMARDs, biologics, and other immunosuppressants, which help manage the underlying disease and minimize steroid side effects [1.3.1, 1.3.2].

Common side effects of methotrexate include nausea, fatigue, and mouth sores [1.9.2]. It can also cause more serious issues like liver toxicity and bone marrow suppression, which is why regular blood monitoring is required [1.3.2, 1.9.2].

There are no direct OTC substitutes with the same strength as prednisone. NSAIDs like ibuprofen (Advil) can help with milder inflammation, and topical hydrocortisone cream is a very mild steroid for skin issues, but they are not sufficient for systemic autoimmune diseases [1.2.4, 1.2.5].