Dr. Ahmed Medications used to treat Rheumatoid arthritis aim to:
- Reduce pain and inflammation and hence improve mobility and quality of life
- Prevent joint damage and joint deformities and maintains normal functions
- Prevent other systems and extraarticular manifestations of Rheumatoid arthritis such as the lungs, eyes, heart, and kidneys
- Achieve remission so that the person can live a normal medication-free life.
The treatment of Rheumatoid arthritis is now patient-centered in which the patient actively makes decisions about his/her treatment options while the doctor only facilitates and gives the best treatment options.
There have been lots of recent advances in the treatment of Rheumatoid arthritis including the use of Biological DMARDS such as IL-6 inhibitors, Tyrosine-kinase inhibitors, and T-cell co-stimulation modulators.
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Here is a list of all the medications used to treat Rheumatoid Arthritis:
Medications Used to Treat Rheumatoid Arthritis | |
| DMARDs | Leflunomide |
| Sulfasalazine | |
| Hydroxychloroquine | |
| Methotrexate | |
| Azathioprine | |
| Cyclosporine | |
| Beta-cell depleting therapy | Rituximab |
| TNF Inhibitors | Infliximab |
| Etanercept | |
| Golimumab | |
| Certolizumab | |
| Adalimumab | |
| IL-1 Inhibitors | Anakinra |
| IL-6 Inhibitors | Tocilizumab |
| Sarilumab | |
| T-cell co-stimulation blockers | Abatacept |
| JAK inhibitors | Tofacitinib |
| Baricitinib | |
| Upadacitinib | |
| Antibiotics | Minocycline |
| NSAIDs (Non-steroidal anti-inflammatory drugs) | Ibuprofen |
| Naproxen | |
| Diclofenac | |
| Ketorolac | |
| Celecoxib | |
| Analgesics | Acetaminophen |
| Opioids | Tramadol |
| Topical skin analgesics | Diclofenac |
| Corticosteroids | Prednisone |
| Methylprednisolone | |
| prednisolone | |
| Chelators | Penicillamine |
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List of Conventional DMARDs used to treat Rheumatoid Arthritis
DMARDs are drugs that are used to modify the course of Rheumatoid arthritis. DMARDs or Disease Modifying anti-rheumatic drugs relieve inflammation, slow joint damage, and prevent long-term disability.
Unlike NSAIDs and corticosteroids, DMARDs work by reducing joint pain and inflammation by suppressing the immune system. In addition, it takes about two to four weeks for most DMARDs to exert their full action compared to NSAIDs and corticosteroids which act instantly.
DMARDs Used to Treat Rheumatoid Arthritis | |
| DMARDs | Leflunomide |
| Sulfasalazine | |
| Hydroxychloroquine | |
| Methotrexate | |
| Azathioprine | |
| Cyclosporine | |
Leflunomide
Leflunomide is a DMARD that is used as monotherapy or in combination with methotrexate for the treatment of Rheumatoid arthritis.
It may be used as a first-line drug in patients who are intolerant or non-responsive to other DMARDs.
| Generic Name | Leflunomide |
| Trade Name | Arava |
| Company Name | Hoechst Marion Roussel, Sanofi Aventis US, Abhai LLC, AET Pharma, Alembic Pharms LTD, Apotex INC, Lupin LTD |
| Date of Approval | September 10, 1998 [ref] |
| Mechanism of action of Leflunomide | |
| Leflunomide’s active metabolite, A771726, can inhibit the human enzyme dihydroorotate dehydrogenase (DHODH) and has antiproliferative properties. | |
| Uses of Leflunomide | |
| Leflunomide is used to treat active rheumatoid arthritis symptoms such as edema, stiffness, inflammation, and joint discomfort. | |
| Major Contraindications: | |
| |
Sulfasalazine
Sulfasalazine has long been used in the treatment of various rheumatological conditions particularly spondyloarthropathies (ankylosing spondylitis).
It may be used as monotherapy or in combination with methotrexate in the treatment of mild to moderate RA.
It can also be used in combination with IL-6 inhibitors such as Tocilizumab in the treatment of moderate to severe Rheumatoid arthritis.
Because more potent and safe alternative medicines used to treat Rheumatoid arthritis are now available, Sulfasalazine is now rarely used.
In addition, it is one of the few DMARDs that is considered safe in the treatment of Rheumatoid Arthritis in pregnancy.
| Generic Name | Sulfasalazine |
| Trade Name | Azulfidine, Azulfidine EN-tabs |
| Company Name | Pfizer Laboratories LTD. |
| Date of Approval | August 18, 2000 [ref] |
| Mechanism of action of Sulfasalazine: | |
| Sulfasalazine is a prodrug broken down into its active ingredients, sulfapyridine and 5-aminosalicylic acid (5-ASA; mesalamine); the anti-inflammatory characteristics of 5-ASA, which blocks the formation of leukotriene and lipoxygenase, are primarily responsible for the beneficial effects. | |
| Uses of Sulfasalazine: | |
| Sulfasalazine alleviates swelling (inflammation). This helps to relieve the symptoms of inflammatory disorders like rheumatoid arthritis. | |
| Major Contraindications: | |
| |
Hydroxychloroquine:
Hydroxychloroquine is an anti-malarial drug. However, it has disease-modifying anti-rheumatic properties.
It is mainly used to relieve symptoms of skin redness and rashes associated with rheumatic diseases especially malar and discoid rashes in patients with SLE.
In the treatment of RA, it is used in the treatment of mild to moderate RA in combination with Methotrexate or other Biological medicines used to treat Rheumatoid Arthritis.
It is one of the few medicines considered safe in the treatment of Rheumatoid Arthritis in Pregnancy.
| Generic Name | Hydroxychloroquine |
| Trade Name | Plaquenil |
| Company Name | Concordia Pharmaceuticals Inc |
| Date of Approval | 1994 [ref] |
| Mechanism of action of Hydroxychloroquine | |
| Antimalarial drugs like hydroxychloroquine have several pharmacological activities that may contribute to their therapeutic benefit in treating rheumatic disease, while the exact nature of each activity is unknown. These include interactions with sulphydryl groups, suppression of enzymes activity (such as phospholipase, NADH-cytochrome C reductase, cholinesterase, proteases, and hydrolases), DNA binding, stabilization of lysosomal membranes, inhibition of prostaglandin synthesis, inhibition of polymorphonuclear cell chemotaxis and phagocytosis, potential suppression of neutrophil superoxide release and interference with interleukin 1 synthesis from monocytes [ref] | |
| Uses of Hydroxychloroquine | |
| Plaquenil (hydroxychloroquine) is a disease-modifying anti-rheumatic medication (DMARD). It can help with arthritis pain and swelling | |
| Major Contraindications: | |
| Hypersensitivity to 4-aminoquinoline derivatives | |
Methotrexate:
Methotrexate is one of the first-line medicines used to treat Rheumatoid Arthritis. It is indicated for moderate to severe Rheumatoid Arthritis as monotherapy or in combination with Biological Medicines used to treat Rheumatoid Arthritis such as TNF inhibitors and IL-6 inhibitors (Tocilizumab).
Methotrexate relieves joint inflammation, pain, and long-term disability and joint deformities in patients with Rheumatoid arthritis.
In addition, because of its weekly oral or subcutaneous administration, it is associated with better drug compliance and tolerance.
| Generic Name | Methotrexate |
| Trade Name | Rheumatrex, Trexall, Otrexup |
| Company Name | Pfizer Laboratories LTD. |
| Date of Approval | 1988 [ref] |
| Mechanism of action of Methotrexate | |
| Inhibition of DHFR is not believed to be the primary mechanism for the treatment of rheumatoid arthritis; instead, several mechanisms seem to be involved, inhibits purine and thymidylic acid synthesis, interfering with DNA synthesis, repair, and cellular replication; cell cycle specific for S phase of the process. It may inhibit the skin’s epithelial cells from proliferating quickly. | |
| Uses of Methotrexate | |
| Methotrexate soothes your immune system, preventing it from attacking your body’s cells. This helps to lessen the inflammation that causes swollen and stiff joints in rheumatoid arthritis. Methotrexate is not a pain reliever. It is used to treat:
| |
| Major Contraindications: | |
| |
Azathioprine
Azathioprine (Imuran) is another DMARD, like Methotrexate. However, it is only used as an alternative to Methotrexate in people who can not tolerate methotrexate.
Azathioprine is mainly used in the treatment of patients with SLE and Interstitial lung diseases, or as a steroid-sparing drug in various conditions including ITP.
It is one of the few drugs considered relatively safe during pregnancy.
| Generic Name | Azathioprine |
| Trade Name | Imuran |
| Company Name | Prometheus Laboratories Inc. |
| Date of Approval | – |
| Mechanism of action of Azathioprine: | |
| Purine antimetabolite transformed to 6-MP; may limit DNA, RNA, and protein synthesis; disrupts cellular metabolism; may inhibit mitosis. | |
| Uses of Azathioprine: | |
| It is used to treat severe rheumatoid arthritis when other drugs and treatments have proven ineffective. | |
| Major Contraindications: | |
| |
Cyclosporine
Cyclosporin is another DMARD that is mainly used in the treatment of rheumatological conditions. However, in the treatment of RA, it is generally considered less effective than Methotrexate.
In addition, cyclosporin is associated with significant side effects such as hypertension, and kidney damage, and increases the risks of infections.
Cyclosporin is generally reserved as a second or third-line DMARD in people who are intolerant to or unresponsive to other DMARDs.
| Generic Name | Cyclosporine |
| Trade Name | Gengraf, Neoral |
| Company Name | Novartis Pharmaceuticals. |
| Date of Approval | January 13, 2000 [ref] |
| Mechanism of action of Cyclosporine: | |
| Cyclosporine acts as a P-glycoprotein inhibitor, a calcineurin inhibitor, and a cytochrome P450 3A4 inhibitor. Cyclosporin A (CsA) prevents the production of interleukins (IL), notably IL-2, which is necessary for the self-activation and differentiation of T lymphocytes (LT). | |
| Uses of Cyclosporine: | |
| It is used for the therapy of rheumatoid arthritis and other autoimmune and inflammatory diseases, including psoriatic arthritis and lupus. | |
| Major Contraindications: | |
| |
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Anti-CD20 antibodies for Rheumatoid Arthritis:
| Beta-cell depleting therapy | Rituximab |
Rituximab:
Rituximab is a monoclonal antibody that binds to CD-20 positive B-cells and induces apoptosis in these cells.
Rituximab is, thus, a B-cell-depleting therapy. By depleting B-cells, antibody production is inhibited.
Antibodies against the synovium of joints are inhibited resulting in a reduction in inflammation and joint damage.
Rituximab is used as monotherapy or in combination with methotrexate in patients who poorly respond to methotrexate or other DMARDs medicines to treat Rheumatoid Arthritis.
Rituximab is one of the few biological medications considered safe for the treatment of Rheumatoid Arthritis in pregnancy.
| Generic Name | Rituximab |
| Trade Name | Rituxan |
| Company Name | IDEC Pharmaceuticals |
| Date of Approval | 1997 [ref] |
| Mechanism of action of Rituximab | |
| A humanized monoclonal antibody that binds to the CD20 antigen and causes complement- or antibody-mediated cytolysis. | |
| Uses of Rituximab | |
| |
| Major Contraindications: | |
| Active Infections (Hepatitis B, Tuberculosis) | |
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IL-6 and IL-1 Inhibitors for RA:
| IL-6 Inhibitors | Tocilizumab |
| Sarilumab | |
| IL-1 Inhibitors | Anakinra |
Tocilizumab:
Tocilizumab is a Biological Medicine used to treat moderate to severe Rheumatoid Arthritis in patients who have poorly responded to other modalities of treatment including methotrexate.
It binds to IL-6 receptor-positive cells and inhibits their action. IL-6 plays a key role in the activation of cytokines and TNFs and recruits cells to the site of inflammation.
Inhibition of IL-6 prevents the signaling, activation, and recruitment of all the immune activities that are dependent on IL-6 and prevents joint damage.
Tocilizumab may be used in combination with Methotrexate or as monotherapy in patients with moderate to severe RA who have not adequately responded to methotrexate or other first-line drugs.
| Generic Name | Tocilizumab |
| Trade Name | Actemra |
| Company Name | Genentech, Inc. |
| Date of Approval | January 10, 2010 [ref] |
| Mechanism of action of Tocilizumab: | |
| Interleukin-6 receptor antagonist. T- and B-cells, lymphocytes, monocytes, and fibroblasts all release the pleiotropic proinflammatory cytokine IL-6. Numerous physiological activities, including T-cell activation, immunoglobulin secretion induction, the beginning of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation, have been linked to IL-6. Additionally, synovial and endothelial cells create IL-6, resulting in a local generation of IL-6 in joints experiencing inflammatory processes. | |
| Uses of Tocilizumab: | |
| This alleviates arthritis-related joint pain and swelling, as well as other inflammation-related symptoms. | |
| Major Contraindications: | |
| Hypersensitivity reactions | |
Sarilumab:
Sarilumab is another IL-6 inhibitor like Tocilizumab. It has a similar mechanism of action in the treatment of patients with Rheumatoid Arthritis.
Tocilizumab is available both as IV and S/C formulation while Sarilumab is only available as a subcutaneous injection.
Sarilumab is associated with an increased risk of infections such as pneumonia and cellulitis while Tocilizumab is associated with more gastrointestinal infections.
Sarilumab, like Tocilizumab, is only indicated in patients with moderate to severe RA who have not adequately responded to methotrexate or other first-line medicines.
| Generic Name | Sarilumab |
| Trade Name | Kevzara |
| Company Name | Sanofi and Regeneron Pharmaceuticals, Inc |
| Date of Approval | May 22, 2017 [ref] |
| Mechanism of action of Sarilumab | |
| Sarilumab is a human monoclonal IgG1 antibody that adheres to both types of interleukin 6 receptors (IL-6R) and blocks IL-6-mediated signaling. IL-6 is a pleiotropic cytokine that stimulates immune cells (T and B cells) as well as hepatocytes to release acute phase proteins such as CRP, serum amyloid A, and fibrinogen, which are indicators of RA activity. IL-6 is also detected in synovial fluid and plays a significant part in the pathological inflammation and joint degradation aspects of RA. Because of its potential to decrease intra-articular and systemic IL-6 signaling, it is used to treat RA. | |
| Uses of Sarilumab | |
| it helps lessen the swelling (inflammation) in rheumatoid arthritis-affected areas. | |
| Major Contraindications: | |
| Hypersensitivity to drug or inactive ingredients. Active infections. | |
Anakinra:
Anakinra is a recombinant form of human IL-1R. It binds to IL-1 Receptors and inhibits the downstream signaling pathways that are involved in the inflammation and joint destruction in patients with RA.
Anakinra may help people with RA who have elevated IL-1 levels and who are not responsive to other first-line medications like Methotrexate.
It may be preferred in patients who are intolerant to or non-responsive to the effects of TNF inhibitors.
There is little experience with the use of Anakinra compared to TNF inhibitors. In addition, it is associated with significant allergic reactions and injection-site reactions.
| Generic Name | Anakinra |
| Trade Name | Kineret |
| Company Name | Swedish Orphan Biovitrum (Sobi) / Savient Pharmaceuticals |
| Date of Approval | November 14, 2001[ref] |
| Mechanism of action of Anakinra | |
| Anakinra is an inhibitor of the Interleukin-1 receptor (recombinant E. coli-derived product). It inhibits IL-1 alpha and beta activity by competitively blocking IL-1 binding to the IL-1 type I receptor. IL-1 production is stimulated by inflammatory stimuli and promotes a variety of physiological responses, including inflammatory and immunological responses. The proteolytic maturation and production of IL-1 beta play a crucial role in systemic inflammation and NOMID symptoms. DIRA is an autosomal recessive monogenic autoinflammatory disease caused by IL1RN gene mutations that result in IL-1Ra secretion loss. | |
| Uses of Anakinra: | |
| Anakinra reduces the signs and symptoms of moderate to severe active rheumatoid arthritis (RA) and slows the progression of damage in patients aged 18 and older when one or more other RA medications have failed. | |
| Major Contraindications: | |
| Hypersensitivity to Kineret, E. coli-derived proteins, or any other product ingredient | |
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T-cell co-stimulation modulators for RA:
| T-cell co-stimulation blockers | Abatacept |
Abatacept:
Abatacept (Orencia) has a different mechanism of action than other biological DMARDs. It is a selective T-cell co-stimulation modulator that inhibits the activation of T-cells responsible for damaging joints in RA.
It is one of the well-tolerated Biological DMARDs medicines used to treat Rheumatoid arthritis that is less likely to be associated with infections.
It is one of the preferred medicines in patients who are intolerant to or non-responsive to methotrexate and TNF inhibitors.
In addition, it is available both as intravenous and subcutaneous formulations and is considered safe for treating Rheumatoid Arthritis during pregnancy.
| Generic Name | Abatacept |
| Trade Name | Orencia |
| Company Name | Bristol-Myers Squibb Company, Princeton, NJ. |
| Date of Approval | December 23, 2005 [ref] |
| Mechanism of action of Abatacept | |
| Abatacept is a selective costimulation modulator that, has been demonstrated to decrease T-cell activation by binding to CD80 and CD86, thereby preventing interaction with CD28. This interaction has been found to hinder the delivery of the second co-stimulatory signal essential for effective T-cell activation. This inhibits autoimmune T-Cell activation, which has been implicated in the pathogenesis of rheumatoid arthritis. | |
| Uses of Abatacept: | |
| Abatacept is indicated for the treatment of moderate to severely active Rheumatoid arthritis in patients who fail to respond to TNF inhibitors or develop side effects to TNF inhibitors. | |
| Major Contraindications: | |
| None | |
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TNF Inhibitors for RA:
| TNF Inhibitors | Infliximab |
| Etanercept | |
| Golimumab | |
| Certolizumab | |
| Adalimumab |
Infliximab:
Infliximab is one of the first TNF inhibitors that was approved for the treatment of Rheumatoid Arthritis followed by Etanercept.
Both Infliximab (Remicade) and Etanercept (Enbrel) are indicated for the treatment of moderate to severe RA who have failed to respond to methotrexate.
However, infliximab is only available in intravenous formulations while Etanercept is available as a subcutaneous injection. Infliximab is only administered in hospital settings while Etanercept can be administered by the patients themselves.
Infliximab, like most other TNF inhibitors, is considered safe for treating Rheumatoid Arthritis during pregnancy.
| Generic Name | Infliximab |
| Trade Name | Remicade, Inflectra, infliximab-dyyb, Renflexis, infliximab-abda, Ixifi, infliximab-qbtx |
| Company Name | Janssen Biotech, Inc., Pfizer Laboratories LTD |
| Date of Approval | 1999 [ref] |
| Mechanism of action of Infliximab: | |
| Infliximab suppresses TNF-α activity via binding to the transmembrane and soluble forms of the protein, as well as inhibiting TNF-α from interacting with its receptor. TNF-α’s biological actions include the induction of inflammatory cytokines such as interleukin-1 (IL-1) and IL-6, the facilitation of leukocyte migration, the induction of eosinophil and neutrophil activity, and the stimulation of acute-phase reactants and tissue-degrading enzymes. | |
| Uses of Infliximab | |
| For the therapy of arthritic disorders as infliximab decreases the flow of inflammatory cells into inflamed regions of the joints, which reduces the signs and symptoms of the condition, improves physical function, reduces joint damage, and lowers the level of other inflammatory indicators | |
| Major Contraindications: | |
| |
Etanercept
Etanercept (Enbrel) is one of the most commonly used TNF inhibitors used to treat Rheumatoid arthritis.
It is indicated for the treatment of moderate to severe RA in patients who are intolerant to or non-responsive to methotrexate or other first-line medications.
Etanercept is available as a subcutaneous injection which makes it easier for patients to self-administer it at home.
In addition, it is considered safe for use during pregnancy.
| Generic Name | Etanercept |
| Trade Name | Enbrel, Erelzi, Etanercept-szzs |
| Company Name | Sandoz |
| Date of Approval | August 30, 2016 [ref] |
| Mechanism of action of Etanercept | |
| Etanercept is a biological tumor necrosis factor (TNF) inhibitor. TNF is a cytokine that is involved in inflammation and the immune response and can connect to TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2). Etanercept acts by inhibiting TNF-alpha, a pro-inflammatory cytokine that is increased in rheumatoid arthritis. | |
| Uses of Etanercept | |
| Injections of etanercept are used to lessen the signs and symptoms of psoriatic, rheumatoid, and active arthritis, such as joint pain, edema, fatigue, and the length of morning stiffness. This medication may also reduce the progression of harm to the body caused by active arthritis or rheumatoid arthritis. | |
| Major Contraindications: | |
| |
Golimumab
Golimumab is a TNF inhibitor that is indicated for the treatment of moderate to severely active Rheumatoid Arthritis in combination with other drugs like methotrexate or as monotherapy.
The efficacy of Golimumab has been comparable to Etanercept in the treatment of RA. However, some studies found Golimumab more effective than Etanercept.
| Generic Name | Golimumab |
| Trade Name | Simponi, Simponi Aria |
| Company Name | Janssen Biotech, Inc. |
| Date of Approval | April 2009 [ref] |
| Mechanism of action of Golimumab: | |
| Human anti-TNF-alpha monoclonal antibody binds to both soluble and transmembrane bioactive forms of human TNFα; blocks TNF-alpha binding to its receptors, hence inhibiting TNF biological activity (a cytokine protein). | |
| Uses of Golimumab: | |
| Golimumab is a TNF inhibitor that is used to treat the symptoms of several active inflammatory illnesses, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis | |
| Major Contraindications: | |
| None | |
Certolizumab:
Certolizumab (Cimzia) is another TNF inhibitor that prevents joint destruction and disability in patients with moderate to severely active Rheumatoid arthritis.
It is one of the safe medications used to treat Rheumatoid arthritis in pregnancy as it does not cross the placental barrier.
In addition, it is considered equally effective in the treatment of RA compared to Etanercept. Rather some studies have found it more effective than Etanercept.
| Generic Name | Certolizumab |
| Trade Name | Cimzia |
| Company Name | UCB Group of Companies |
| Date of Approval | April 22, 2008 [ref] |
| Mechanism of action of Certolizumab | |
| Certolizumab pegol binds to both soluble and membrane-bound TNF-α, reducing the cytokine’s proinflammatory activities. In contrast to other TNFi, it is unable to fix complement or bind to Fc receptors because it lacks the Fc component | |
| Uses of Certolizumab | |
| Certolizumab is used in the treatment of Ankylosing spondylitis and psoriatic arthritis apart from Rheumatoid arthritis. | |
| Major Contraindications: | |
| |
Adalimumab:
Adalimumab (Humira) is one of the most studied drugs in the treatment of RA. It is more effective than conventional DMARDs for RA treatment.
Adalimumab is administered once every two weeks as a subcutaneous injection. It is also considered safe for use in pregnancy.
| Generic Name | Adalimumab |
| Trade Name | Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz |
| Company Name | AbbVie Inc. |
| Date of Approval | December 31, 2002 [ref] |
| Mechanism of action of Adalimumab | |
| Adalimumab is a Recombinant human anti-TNF-α IgG1 monoclonal antibody; blocks TNF-α’s ability to cause inflammation; it binds to TNF-α selectivity and prevents it from interacting with the p55 and p75 cell surface TNF receptors; lyses surface TNF-expressing cells in vitro; and modifies the biological processes that control leukocyte migration. | |
| Uses of Adalimumab | |
| This is recommended for adult patients with moderately to severely active rheumatoid arthritis to lessen signs and symptoms, induce a significant clinical response, stop the progression of structural damage, and enhance physical function. HUMIRA can be taken alone or in conjunction with methotrexate or other nonbiologic disease-modifying anti-rheumatic medications (DMARDs). It is also used to treat psoriatic arthritis and ankylosing spondylitis, Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), and Hidradenitis suppurativa. | |
| Major Contraindications: | |
| None | |
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JAK Inhibitors for RA:
| JAK inhibitors | Tofacitinib |
| Baricitinib | |
| Upadacitinib |
Tofacitinib:
Tofacitinib is an oral medication, unlike most other biological medications used to treat Rheumatoid Arthritis which are administered as either intravenous or subcutaneous injections.
Tofacitinib belongs to a novel class of medicines called JAK-STAT inhibitors. It is recommended for the treatment of patients with moderate to severe Rheumatoid arthritis who have failed to respond to conventional DMARDs such as methotrexate.
It may be used as monotherapy or in combination with methotrexate for the treatment of RA unresponsive to DMARDs alone.
Tofacitinib is not indicated for use in pregnancy. In addition, it is costly and may take time for full effect.
| Generic Name | Tofacitinib |
| Trade Name | Xeljanz, Xeljanz XR |
| Company Name | Pfizer Inc. |
| Date of Approval | 2012 [ref] |
| Mechanism of action of Tofacitinib: | |
| Tofacitinib is a partial and reversible JAK inhibitor that prevents the body from reacting to cytokine signals. Tofacitinib suppresses the phosphorylation and activation of STATs by inhibiting JAKs. The JAK-STAT signaling pathway is involved in the transcription of cells engaged in hematopoiesis and immune cell activity. Tofacitinib reduces inflammation by blocking the JAK-STAT pathway. | |
| Uses of Tofacitinib: | |
| To reduce inflammation in the joints caused by rheumatoid arthritis tofacitinib is the most frequently used jak inhibitor. In addition, it is used to treat:
| |
| Major Contraindications: | |
| None | |
Baricitinib:
Baricitinib is an oral JAK-STAT inhibitor like Tofacitinib. It is taken in a dose of 2 mg orally once daily with or without food.
Baricitinib is approved by the FDA for the treatment of moderate to severely active Rheumatoid Arthritis and atopic dermatitis.
Baricitinib is not indicated in patients with severe hepatic impairment and those on concomitant strong CYP3A4 inhibitors.
| Generic Name | Baricitinib |
| Trade Name | Olumiant |
| Company Name | Eli Lilly and Incyte Corporation |
| Date of Approval | May 2018 [ref] |
| Mechanism of action of Baricitinib | |
| Baricitinib is a reversible and selective Janus Kinase inhibitor that is taken orally (JAKs). Janus Kinase is an intracellular enzyme that belongs to the tyrosine-protein kinase family that controls signals from cytokines and growth factor receptors involved in immune cell activity. These JAK dimers phosphorylate transcription factors (STATs) and activate intracellular activity, including gene transcription, of inflammatory mediators, resulting in an autoimmune response. Baricitinib has a greater affinity for JAK1 and JAK2. It inhibits JAK proteins, prevents STAT phosphorylation and activation, and regulates the signaling pathways of different interleukins, interferons, and growth factors. Baricitinib also reduces the proliferation of JAK1/JAK2 expression in mutant cells and produces cell death. | |
| Uses of Baricitinib | |
| Olumiant is a Janus kinase (JAK) inhibitor approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have not responded adequately to one or more TNF blockers. | |
| Major Contraindications: | |
| None | |
Upadacitinib:
Upadacitinib (Rinvoq) is one of the latest approved medications used to treat Rheumatoid arthritis. Compared to other DMARDs and biological medicines, it has a favorable side effects profile and has the fastest onset of action.
It is indicated for the treatment of moderately to severely active Rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
| Generic Name | Upadacitinib |
| Trade Name | Rinvoq |
| Company Name | AbbVie Ltd. |
| Date of Approval | 2019 [ref] |
| Mechanism of action of Upadacitinib: | |
| Upadacitinib is a JAK1 inhibitor. JAK1 is required for specific cytokines to elicit signals from various interleukins, neurotrophins, interferons, and cardiotrophins. These signals are critical in the maintenance of the inflammatory condition in rheumatoid arthritis (RA); inhibiting JAK reduces the synthesis of and modifies proinflammatory cytokines that are key to RA. | |
| Uses of Upadacitinib: | |
| Upadacitinib is intended for the treatment of persons with moderately to severely active rheumatoid arthritis who have had an insufficient response or intolerance to one or more TNF blockers. It is also indicated for the treatment of psoriatic arthritis and ankylosing spondylitis. | |
| Major Contraindications: | |
| Hypersensitivity to Upadacitinib and its excipient. | |
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Antibiotics DMARDs for RA:
| Antibiotics | Minocycline |
Minocycline
Minocycline is a tetracycline antibiotic that is indicated for treating various bacterial infections such as acne and other infections.
It has been proven to have anti-inflammatory properties and improves joint function, however, it is not approved for treating Rheumatoid arthritis.
| Generic Name | Minocycline |
| Trade Name | Dynacin, Minocin |
| Company Name | Par Pharmaceutical, Inc |
| Date of Approval | May 31, 2002 [ref] |
| Mechanism of action of Minocycline: | |
| The mechanism of action of minocycline in cases of rheumatoid arthritis is not fully known; it may have immunomodulatory, anti-inflammatory, or chondroprotective properties. It is thought to be a powerful inhibitor of metalloproteinases, which are involved in the degradation of joints in rheumatoid arthritis. | |
| Uses of Minocycline: | |
| This drug is used either alone or in combination with other medications to treat rheumatoid arthritis. | |
| Major Contraindications: | |
| Hypersensitivity | |
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NSAIDs for RA:
| NSAIDs (Non-steroidal anti-inflammatory drugs) | Ibuprofen |
| Naproxen | |
| Diclofenac | |
| Ketorolac | |
| Celecoxib |
Ibuprofen:
Ibuprofen is a non-selective non-steroidal anti-inflammatory drug. It is available as an OTC medicine and used for pain relief in patients with Rheumatoid arthritis.
It has a faster onset of action but because of its shorter half-life, it is administered more frequently.
| Generic Name | Ibuprofen |
| Trade Name | Advil, Motrin |
| Company Name | Pfizer Inc., Wyeth Pharmaceuticals Company |
| Date of Approval | – |
| Mechanism of action of Ibuprofen: | |
| Inhibits prostaglandin formation in bodily tissues by inhibiting at least two cyclo-oxygenases (COX) isoenzymes, COX-1 and COX-2. May block chemotaxis, modify lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory efficacy. | |
| Uses of Ibuprofen: | |
| Ibuprofen is a nonsteroidal anti-inflammatory medicine (NSAID) used to treat mild to moderate pain. It also aids in reducing inflammation, edema, stiffness, and joint discomfort that are signs of arthritis (osteoarthritis, rheumatoid arthritis, or juvenile arthritis). | |
| Major Contraindications: | |
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Naproxen:
Naproxen is another non-selective NSAID. It is more potent than Ibuprofen and has the advantage of twice or thrice daily dosing.
Naproxen has a comparably safer GI side effects profile but Ibuprofen is safer in patients with kidney disease and hypertension.
| Generic Name | Naproxen |
| Trade Name | Naprosyn, Aleve, Anaprox DS, Naprelan |
| Company Name | Bayer HealthCare, Banner Pharmacaps Inc. |
| Date of Approval | April 30, 2010 [ref] |
| Mechanism of action of Naproxen: | |
| Inhibits prostaglandin formation in bodily tissues by inhibiting at least two cyclooxygenases (COX) isoenzymes, COX-1 and COX-2. These effects may contribute to anti-inflammatory efficacy by inhibiting chemotaxis, altering lymphocyte function, decreasing proinflammatory cytokine activity, and inhibiting neutrophil aggregation. | |
| Uses of Naproxen: | |
| It is used in the therapy of rheumatoid arthritis, osteoarthritis, or juvenile arthritis. | |
| Major Contraindications: | |
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Diclofenac:
Diclofenac, like Naproxen, is a longer-acting drug and can be administered twice or thrice daily. However, it has more GI side effects and may not be suitable for patients with cardiovascular diseases compared to Naproxen.
| Generic Name | Diclofenac |
| Trade Name | Voltaren, Cambia |
| Company Name | GlaxoSmithKline (GSK), Kowa Pharmaceuticals America, Inc. |
| Date of Approval | |
| Mechanism of action of Diclofenac: | |
| Inhibits cyclooxygenase (COX)-1 and COX-2, consequently inhibiting prostaglandin production. It may also suppress neutrophil aggregation/activation, chemotaxis, proinflammatory cytokine levels, and alter lymphocyte activity. | |
| Uses of Diclofenac: | |
| It is used to alleviate pain associated with conditions like rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis when taken orally. | |
| Major Contraindications: | |
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Ketoprofen:
Ketoprofen is a non-selective NSAID that is used to relieve inflammation, joint pain, and swelling. Compared to ibuprofen, ketoprofen is a more strong NSAID.
It relieves pain and inflammation in the joints more effectively than ibuprofen at the cost of more severe adverse gastrointestinal side effects.
| Generic Name | Ketoprofen |
| Trade Name | Orudis, Orudis KT, Oruvail |
| Company Name | Wyeth Pharmaceuticals. |
| Date of Approval | November 25, 2009 [ref] |
| Mechanism of action of Ketoprofen: | |
| Inhibits prostaglandin synthesis in body tissues by inhibiting at least two cyclooxygenase isoenzymes, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) (COX-2). May reduce pro-inflammatory cytokine activity, inhibit neutrophil aggregation, inhibit chemotaxis, and change lymphocyte function. These properties may help to explain its anti-inflammatory efficacy. | |
| Uses of Ketoprofen: | |
| It is used in the therapy of rheumatoid arthritis. | |
| Major Contraindications: | |
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Celecoxib:
Celecoxib is a longer-acting selective COX inhibitor. It has the safest GI side effects profile. It can be easily tolerated by patients who have stomach ulcers or gastrointestinal symptoms like heartburn and GI bleeding.
Celecoxib is equally effective as Naproxen for pain relief but there are cardiovascular risks associated with it.
| Generic Name | Celecoxib |
| Trade Name | Celebrex |
| Company Name | Pfizer Inc. |
| Date of Approval | December 23, 1999 [ref] |
| Mechanism of action of Celecoxib: | |
| Inhibits cyclooxygenase (COX)-2 and does not affect COX-1 (at therapeutic dosages), thereby reducing prostaglandin production. | |
| Uses of Celecoxib: | |
| It is used for the therapy of rheumatoid arthritis, osteoarthritis, and juvenile rheumatoid arthritis. | |
| Major Contraindications: | |
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Topical NSAIDs for RA
| Topical skin analgesics | Diclofenac |
Diclofenac topical
Topical NSAIDs like Topical Diclofenac may be used when a limited number of joints are inflamed. Topical diclofenac is applied directly over the joints which are then absorbed and relieve localized pain.
It is preferred when the symptoms are mild and patients are intolerant to oral medications used to treat Rheumatoid arthritis because of gastrointestinal side effects.
| Generic Name | Diclofenac topical |
| Trade Name | Voltaren |
| Company Name | GlaxoSmithKline (GSK) |
| Date of Approval | 2007 [ref] |
| Mechanism of action of Diclofenac topical: | |
| Reduces prostaglandin synthesis by inhibiting cyclooxygenase enzymes 1 and 2; may have anti-inflammatory effects by suppressing chemotaxis, neutrophil aggregation/activation, and proinflammatory cytokine levels. | |
| Uses of Diclofenac topical: | |
| Voltaren gel, which is used topically (to the skin), is particularly effective for osteoarthritis of the knees and hands. | |
| Major Contraindications: | |
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Acetaminophen
Acetaminophen (Paracetamol) is not an anti-inflammatory drug and hence is less effective in relieving pain and inflammation.
However, it is safe in patients with kidney and cardiovascular disease and is a better option for use in the long run.
In addition, it can be combined with any NSAID, DMARD, or biological medications used to treat RA.
| Generic Name | Acetaminophen |
| Trade Name | Tylenol |
| Company Name | McNeil Consumer Healthcare |
| Date of Approval | March 19, 2002 [ref] |
| Mechanism of action of Acetaminophen: | |
| Acts on the hypothalamus to induce antipyresis. May act peripherally to reduce pain impulse production; may also inhibit prostaglandin synthesis in the CNS. | |
| Uses of Acetaminophen: | |
| It is used in the therapy of rheumatoid arthritis. | |
| Major Contraindications: | |
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Tramadol
Tramadol is an opioid analgesic with addictive properties. Like Acetaminophen, it does not possess anti-inflammatory properties and hence may not be very effective in relieving pain due to inflamed joints.
It is safe for use in patients with kidney disease and may be used as an adjunct with NSAIDs, DMARDs, or Biological medications for pain relief when other medicines have not been effective.
| Generic Name | Tramadol |
| Trade Name | Ultram |
| Company Name | Grünenthal GmbH |
| Date of Approval | September 8, 2005 [ref] |
| Mechanism of action of Tramadol: | |
| Non-opioid-derived synthetic opioid; centrally acting analgesic, but may work in part by binding to opioid mu receptors, inhibiting ascending pain pathways. | |
| Uses of Tramadol: | |
| It is used for the treatment of severe pain associated with rheumatoid arthritis. | |
| Major Contraindications: | |
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Corticosteroids for RA:
| Corticosteroids | Prednisone |
| Methylprednisolone | |
| prednisolone |
Prednisone
Prednisone is a prodrug that is converted in the body by hepatic enzymes into prednisolone. Prednisone is a corticosteroid that has strong anti-inflammatory properties.
However, like all other corticosteroids, prednisone is associated with multiple systemic side effects including diabetes, hypertension, osteoporosis, infections, and peptic ulcers.
Prednisone is used for rapid pain relief in patients who are markedly symptomatic and have marked restrictions in mobility due to pain.
| Generic Name | Prednisone |
| Trade Name | Rayos, Prednisone Intensol |
| Company Name | Horizon Pharma, Inc. |
| Date of Approval | July 26, 2012 [ref] |
| Mechanism of action of Prednisone: | |
| Prednisone is a Glucocorticosteroid; evokes mild mineralocorticoid activity and moderate anti-inflammatory effects; It controls or restricts inflammation by regulating protein synthesis, reversing capillary permeability, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, and stabilizing lysosomes at the cellular level; Corticosteroids are given in physiologic amounts to replace low levels of endogenous hormones, and at higher (pharmacologic) dosages, they reduce inflammation. | |
| Uses of Prednisone: | |
| Prednisone can benefit RA patients who are having a severe flare. Patients with rheumatoid arthritis who have not responded well to DMARDs or biologics may also be offered prednisone. | |
| Major Contraindications: | |
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Methylprednisolone
Methylprednisolone is another potent corticosteroid. It is considered more potent than prednisone and prednisolone.
It is available in oral, intravenous, and DEPOT IM formulations. The duration of action of depo formulations lasts for two to three weeks and may be preferred in patients who have gastrointestinal side effects due to oral prednisolone.
| Generic Name | Methylprednisolone |
| Trade Name | Depo-Medrol, Medrol, Solu-Medrol |
| Company Name | Pfizer laboratories LTD. |
| Date of Approval | |
| Mechanism of action of Methylprednisolone: | |
| A potent glucocorticoid with negligible to zero mineralocorticoid activity. Maintains fluid and electrolyte balance and modifies the metabolism of carbohydrates, proteins, and lipids. Regulates or prevents inflammation by modulating the rate of protein synthesis, preventing the migration of fibroblasts and polymorphonuclear leukocytes (PMNs), reversing capillary permeability, and stabilizing lysosomes at the cellular level. | |
| Uses of Methylprednisolone: | |
| It is used to treat acute rheumatic carditis, acute gout, ankylosing spondylitis, dermatomyositis and polymyositis, psoriatic arthritis, and rheumatoid arthritis, including juvenile rheumatoid arthritis and systemic lupus erythematosus. | |
| Major Contraindications: | |
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Prednisolone
Prednisolone is the active drug of prednisone. It has a quicker onset of action than prednisone and is considered to be more effective in reducing pain and inflammation compared to prednisone.
However, it has a shorter duration of action and may need to be given more frequently compared to prednisone.
In addition, it is only available as oral tablets and syrups and may have more gastrointestinal side effects compared to parenteral methylprednisolone.
| Generic Name | Prednisolone |
| Trade Name | Orapred ODT, Pediapred |
| Company Name | BioMarin Pharmaceutical Inc./Alliant Pharmaceuticals, Inc. |
| Date of Approval | June 2, 2006 [ref] |
| Mechanism of action of Prednisolone: | |
| Glucocorticosteroid; induces mild mineralocorticoid activity and moderate anti-inflammatory effects; It controls or restricts inflammation by regulating protein synthesis, reversing capillary permeability, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, and stabilizing lysosomes at the cellular level. | |
| Uses of Prednisolone: | |
| It is frequently used to treat a wide range of inflammatory diseases, such as redness, swelling, and pain. This medication is used to treat rheumatoid arthritis, lupus, vasculitis, and a variety of other inflammatory illnesses. | |
| Major Contraindications: | |
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Chelators for RA:
| Chelators | Penicillamine |
Penicillamine
Penicillamine is now rarely used to treat RA. It is more commonly used in patients with Wilson’s disease and copper toxicity.
Penicillamine is said to have a weak DMARD-like effect. It inhibits inflammatory cells at the site of inflamed joints.
However, it is associated with significant side effects including rash, renal failure, bone marrow failure, and drug-induced lupus.
| Generic Name | Penicillamine |
| Trade Name | Cuprimine, Depen |
| Company Name | Meda Pharmaceuticals Inc., Bausch Health Companies Inc. |
| Date of Approval | October 26, 2004 [ref] |
| Mechanism of action of Penicillamine: | |
| Penicillamine can chelate heavy metals such as lead, copper, and mercury, forming a soluble complex that is eliminated in the urine via the kidneys. It also binds to cysteine and creates disulfide bonds with it, facilitating the excretion of cysteine-penicillamine complexes rather than cysteine. It can suppress T cell activation in rheumatoid arthritis, while the specific mechanism of action is uncertain. | |
| Uses of Penicillamine: | |
| It is also used in conjunction with other medicines to treat severe rheumatoid arthritis (a disorder in which the body’s immune system attacks its joints, producing pain, swelling, and loss of function) that has not responded to conventional treatments. | |
| Major Contraindications: | |
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