| Medications for Scleroderma, Arthritis,
Autoimmune and Rheumatic Diseases |
| This page was written by Janey Willis and has not yet been medically edited. See Disclaimer. |
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| Immunosuppresants |
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| Overview of Immunosuppressants |
| Immunosuppressants are medications that suppress or prevent the immune response. Immunosuppressants are used to prevent rejection of a transplanted organ and to treat autoimmune diseases such as scleroderma, psoriasis, rheumatoid arthritis, and Crohn's disease. They are also referred to as immunodepressants. |
| Some immunosuppressants are chemotherapy drugs, but used at higher dosages than when used to treat autoimmune disease. |
| Immunosuppressants fall under a category of drugs referred to as DMARDs (Disease-Modifying Anti-Rheumatic Drugs). Immunosuppressants commonly used for scleroderma and rheumatic diseases include methotrexate, azathioprine (Imuran), cyclosporine, mycophenolate mofetil (Cellcept), and cyclophosphamide (Cytoxan). As with any drugs, immunosuppressants can have serious side effects and risks. |
| Immunosuppressants - clinical applications. There are now over 80 autoimmune diseases and several common allergic conditions in which immunosuppressants could play a role although they may not be life-saving. Australian Prescriber. |
| High frequency of corticosteroid and immunosuppressive therapy in patients with systemic sclerosis despite limited evidence for efficacy. Despite limited evidence for the effectiveness of corticosteroids and immunosuppressive agents in systemic sclerosis, these potentially harmful drugs are frequently prescribed to patients with all forms of systemic sclerosis. Therefore, this study indicates the need to develop and communicate adequate treatment recommendations. N. Hunzelmann Arthritis Research & Therapy, 11:R30. 4 March 2009. (Also see: Steroids) |
| Epstein Barr Virus (EBV)-Associated Primary CNS Lymphomas (PCNSLs) in Elderly Patients on Immunosuppressive Medications. These cases serve as a diagnostic alert for neuropathologists and suggest that increased testing of PCNSLs for EBV by immunohistochemistry or in situ hybridization may be warranted in any patient on any immunosuppressive medication, but particularly the elderly. Kleinschmidt-DeMasters, B.K. MD. Journal of Neuropathology & Experimental Neurology. November 2008. (Also see: Causes of Scleroderma) |
| The Effects of Medications on Bone. Corticosteroids and cancer chemotherapeutic agents generally affect bone adversely and increase fracture. J Am Acad Orthop Surg, Vol 15, No 8, August 2007, 450-460. |
| Advances in immunosuppressive therapy. This represents the first evidence that immunosuppressive drugs are efficacious in rheumatic disease-associated interstitial fibrosis and provides a rationale for developing therapeutic regimens that optimize efficacy and safety. PubMed. Semin Respir Crit Care Med. 2007 Aug;28(4):398-417. (Also see: Pulmonary Fibrosis) |
| Immune Status and Risk for Infection in Patients Receiving Chronic Immunosuppressive Therapy. Patients receiving chronic immunosuppressive therapy can develop severe lymphopenia that involves all subsets. Monitoring T-helper cell counts may be useful to estimate the risk for subsequent infections in such patients. J Rheumatol. 2005 August;32:1473-80. |
| Scleroderma Treatments and Clinical Trials ISN. |
| Azathioprine (Imuran) |
| Azathioprine (Imuran). Patient Education. American College of Rheumatology. |
| Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy. This study suggests a role of AZA in maintaining the improvement induced by low dose pulse CYC in early dcSSc, making it possible a short duration of treatment at a low cumulative dose of the drug. These results, however, await confirmation in controlled studies. PubMed. Clin Exp Rheumatol. 2007 Jul-Aug;25(4):613-6. |
| A randomized unblinded trial of cyclophosphamide CYC) versus azathioprine (AZ) in the treatment of systemic sclerosis. After treatment there was a statistically significant improvement in the modified Rodnan skin score, attack frequency of Raynaud's phenomenon, and erythrocyte sedimentation rate (ESR) in the CYC-group, but not in the AZ-group. PubMed. Clin Rheumatol. 2006 Mar;25(2):205-12. Epub 2005 Oct 14. |
| Cyclophosphamide (Cytoxan) |
| Cyclophosphamide Clinical Trials. ISN. |
| Cyclophosphmide (Cytoxan). Patient Education. drugs.com |
| Cyclophosphamide in systemic sclerosis: still in search of a 'real life' scenario. In systemic sclerosis (SSc), there is no proven treatment to prevent disease progression. In a recent meta-analysis of three randomised controlled trials (RCTs) and six open prospective studies on cyclophosphamide (CYC), no significant changes in lung function were observed. Further RCTs on early SSc are needed to assess the real efficacy of CYC in inducing remission and increasing survival. I. Miniati. Arthritis Research & Therapy 23 January 2009 (Also see: Pulmonary Fibrosis) |
| Cyclophosphamide treatment improves microvessel damage in systemic sclerosis. Cyclophosphamide administration was significantly associated with amelioration of nailfold videocapillaroscopic pattern. P Caramaschi. (SpringerLink) Clinical Rheumatology. December 04, 2008. (Also see: Raynaud's) |
| High dose cyclophosphamide performs better than monthly dose cyclophosphamide in quality of life measures. A randomised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide in patients with Systemic Lupus Erythematosus (SLE) who need cyclophosphamide for the first time. This study shows eventual improvements in quality-of-life with both cyclophosphamide regimens which are clinically meaningful to both patients and treating physicians. (SageJournals) KB Dussán. Lupus. November 25, 2008. (Also see: Lupus) |
| Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and a meta-analysis of randomized controlled trials and observational prospective cohort studies. Cyclophosphamide treatment in patients with systemic sclerosis related interstitial lung disease does not result in clinically significant improvement of pulmonary function. (UnBound) C. Nannini. Arthritis Res Ther 2008 Oct 20; 10(5):R124. (Also see: Clinical Trials, and Pulmonary Fibrosis) |
| Therapeutic Strategy Combining Intravenous Cyclophosphamide (CYC) Followed by Oral Azathioprine to Treat Worsening Interstitial Lung Disease Associated with Systemic Sclerosis: A Retrospective Multicenter Open-label Study. Intravenous CYC followed by oral maintenance immunosuppressive therapy for worsening ILD was well tolerated and was associated with stable or improved PFT in 70% and 51.8% of SSc patients at 6 months and 2 years, respectively. J Rheumatology First Release May 1 2008. (Also see: Pulmonary Fibrosis) |
| Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. One year of CYC improved lung function, skin scores, dyspnea, and health status/disability, effects which either persisted or increased further for several months after stopping therapy. However, except for a sustained impact on dyspnea, all of these effects waned and were no longer apparent at 24 months. PubMed. Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34. (Also see: Cytoxan and Pulmonary Involvement) |
| Cyclosporine |
| Cyclosporine (Neoral, Sandimmune, Gengraf). MedlinePlus.com |
| Licorice Reduces Cyclosporine, Raises Methotrexate Levels. An ingredient in licorice, widely used in foods and herbal medicines, blocks cyclosporine absorption, significantly reducing the drug's serum levels and duration and has the opposite effect on Methotrexate. Janis Kelly, MSK Report, March 2009. (Also see: Licorice and Methotrexate) |
| Hemolytic uremic syndrome with ischemic glomerulonephropathy and obliterative vasculopathy in a systemic sclerosis (SSc) patient treated with cyclosporine-A (CSA). Hemolytic uremic syndrome is not a commonly reported complication in post-transplantation patients treated with CSA, and is extremely rare in SSc patients treated with this drug. Wei-Sheng Chen. Rheumatology International. 21 January 2009. |
| Methotrexate |
| Methotrexate Clinical Trials. ISN. |
| Methotrexate. Patient Education. American College of Rheumatology. |
| Role and place of methotrexate in vasculitis management. Methotrexate is a folic acid analog with a favorable efficacy-to-toxicity ratio that has been used for many years to treat a variety of inflammatory arthropathies, thereby explaining the growing interest in its use for systemic vasculitides. However, it should be prescribed with caution or avoided in vasculitis patients with impaired renal function. (FutureMedicine) C. Pagnoux. International Journal of Clinical Rheumatology. December 2009. (Also see: Vasculitis) |
| Treatment of Pediatric Localized Scleroderma: Results of a Survey of North American Pediatric Rheumatologists (PR). Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease. SC Li. J Rheumatol 2009 Nov 16. (Also see: Juvenile Scleroderma and Localized Scleroderma) |
| Long Term Outcome of 14 Patients with Severe Form of Juvenile Localized Scleroderma (JLS). There are no accurate data on the natural history and optimal management of JLS. Methotrexate appears to be effective therapy in our cohort of patients with severe form of JLS and we propose a larger, multicenter study investigating impact of treatment on the long term outcome of JLS. T. Avcin. (SAT0541) EULAR 2009. (Also see: Juvenile Scleroderma and Localized Scleroderma) |
| Characterization of the Cellular Infiltrate of Localized Scleroderma (LS) skin Lesions Before and After Methotrexate (MTX) or Prednisone Treatment. Juvenile LS active lesions are characterized by infiltration of CD8+ T cell and B cells, which seem to play an important role in the early phases of the disease. MTX treatment significantly reduces the inflammatory infiltrate, re-establish the CD4/CD8 T-cell ratio and induce the B-cell disappearance. F. Lunardi. (SAT0002) EULAR 2009. (Also see: Localized Scleroderma) |
| Licorice Reduces Cyclosporine, Raises Methotrexate Levels. An ingredient in licorice, widely used in foods and herbal medicines, blocks cyclosporine absorption, significantly reducing the drug's serum levels and duration and has the opposite effect on Methotrexate. Janis Kelly, MSK Report, March 2009. (Also see: Licorice and Cyclosporine) |
| Shifting Our Thinking About Uncommon Disease Trials: The Case of Methotrexate in Scleroderma. From the trial data, clinicians can infer that MTX has a high probability of beneficial effects on skin score and global assessment. S. R. Johnson. J Rheumatol First Release Dec 1 2008. |
| Variation of immunological response in methotrexate-induced pneumonitis (MTX-P). Our findings suggest that MTX-P can be divided into two groups: type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and has a high mortality; and type 2 MTX-P that occurs late, predominated by lymphocytes, has less lung fibrosis and low mortality. B. Chikura. Rheumatology 2008 47(11):1647-1650. (Also see: Pulmonary Involvement) |
| A Novel Predictor of Clinical Response to Methotrexate (MTX) in Patients with Rheumatoid Arthritis (RA): A Pilot Study of in Vitro T Cell Cytokine Suppression. An in vitro tumor necrosis factor-a suppression assay may help predict clinical response to MTX in RA. Nigil Haroon. J Rheumatol First Release May 1 2008. (Also see: Rheumatoid Arthritis) |
| Tolerability of methotrexate (MTX) and leflunomide (LEF) combination therapy for inflammatory arthritis in routine clinical practice: results of a four-centre study. The contrasting modes of action of MTX and LEF make them attractive candidates for use in combination with the potential to provide additive or synergistic actions, perhaps without the need for expensive biologic agents. A. Kaul. Rheumatology Advance Access. July 15, 2008. (Also see: Arthritis and DMARDs) |
| Therapy with Immunosuppressive Drugs and Biological Agents and Use of Contraception in Patients with Rheumatic Disease. The increasing use of combination therapies containing Methotrexate necessitates ensuring that advice regarding birth control is followed in order to avoid pregnancies exposed to potentially fetotoxic drugs. J Rheumatol 2007 June;34:1266-9. (Also see: Scleroderma and Pregnancy) |
| Rheumatoid arthritis could be prevented if the timing is right: Methotrexate shown to delay and prevent RA progression. Patients diagnosed with undifferentiated rheumatoid arthritis could have their disease outlook changed if treatment is given at the right time. Innovations Report. 06/22/06. (Also see: Rheumatoid Arthritis) |
| Placebo controlled trial of methotrexate in systemic sclerosis. Clinical improvement following treatment was observed in 33.33% of the patient in MTX group but none in placebo group, but this difference was not statistically significant. PubMed. Mymensingh Med J. 2005 Jan;14(1):71-4. |
| Mycophenolate mofetil (Cellcept) |
| Mycophenolate Mofetil (Cellcept). CellCept lowers your body's immune system. drugs.com |
| A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis. We observed significant improvements in skin scores, peripheral vascular involvement and patient-perceived health status. Pulmonary function studies did not worsen as expected, but instead showed a trend towards improvement. Chris T. Derk. Rheumatology. October 21, 2009. |
| Mycophenolate Mofetil (MMF or Cellcept) in Systemic Sclerosis Associated Interstitial Lung Disease (ILD). There was a significant increase in forced vital capacity (FVC) and a non-significant increase in carbon monoxide diffusing capacity (DLCO) at 12 months in patients on MMF. A. Koutroumpas. (FRI0331) EULAR 2009. (Also see: Pulmonary Fibrosis) |
| Experience of Mycophenolate Mofetil (MMF) in 10 Patients With Autoimmune-Related Interstitial Lung Disease Demonstrates Promising Effects. MMF is safe, well tolerated, and allows reduction or discontinuation of prednisone without worsening of symptoms or objective progression of disease. L. A, Saketkoo, MD American Journal of the Medical Sciences. 337(5):329-335, May 2009. (Also see: Pulmonary Fibrosis) |
| Current Therapies for Lupus Nephritis in an Ethnically Heterogeneous Cohort. After controlling for the fact that less severe nephritis is preferentially treated with mycophenolate mofetil (MMF), we found overall that response to MMF was superior to intravenous cyclophosphamide. T. Rivera. J Rheumatol. Dec 1 2008. (Also see: Lupus) |
| Effect of Mycophenolate Mofetil (MMF) on Pulmonary Function in Scleroderma-Associated Interstitial Lung Disease (SSc-ILD). These retrospective data suggest MMF improves vital capacity (VC) in patients with SSc-ILD. Gerbino AJ, Goss CH, Molitor JA.(PubMed) Chest. 2007 Dec 10. (Also see: Pulmonary Fibrosis) |
| FDA Alert for CellCept (mycophenolate mofetil). Roche and FDA notified healthcare providers that use of CellCept (mycophenolate mofetil) is associated with increased risk of first trimester pregnancy loss and increased risk of congenital malformations. In addition, CellCept reduces blood levels of the hormones in an oral contraceptive pill and could theoretically reduce its effectiveness. FDA Medwatch. October 2007. (Also see: FDA Warnings) |
| 2nd Phase III CellCept Failure Sends Aspreva Shares Down. The 370-patient, 24-week, randomized, open-label study failed to prove that CellCept was superior to intravenous cyclophosphamide (IVC), a cancer drug used off-label in lupus nephritis and widely considered to be the current standard of care. BioWorld Today. 06/28/07. (Also see: Lupus) |
| Mycophenolate Mofetil and Intravenous Dexamethasone in the Treatment of Persistent Lupus Myelitis. Subsequent therapy with mycophenolate mofetil and continuous intravenous infusions of dexamethasone resulted in reduction of the lesion's size, disappearance of magnetic resonance imaging enhancement, and a complete recovery. J Rheumatol 2007;34:588-91 (Also see: Lupus) |
| Warnings and Risks associated with Immunosuppressants |
| RA Patients Could Be Hard Hit By Swine Flu. “This is a serious infection and people with rheumatic and autoimmune diseases taking immunosuppressant agents are at high risk for infections and for the infections to be severe, so they are definitely at higher risk for swine flu [and swine flu-related mortality],” warned Eric Matteson, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota. D.M. Kleinman. Musculoskeletal Report. April 28 2009. |
| Pregnancy and rheumatic diseases. Infertility is rarely due to the disease but can be associated with cyclophosphamide therapy. Most rheumatic diseases that are well controlled prior to pregnancy do not deteriorate in pregnancy, providing that the patient continues with appropriate disease-modifying therapy. Rheumatology 2007 46(11):1634-1640. (Also see: Scleroderma and pregnancy) |
| Therapy with Immunosuppressive Drugs and Biological Agents and Use of Contraception in Patients with Rheumatic Disease. The increasing use of combination therapies containing Methotrexate necessitates ensuring that advice regarding birth control is followed in order to avoid pregnancies exposed to potentially fetotoxic drugs. J Rheumatol 2007 June;34:1266-9. (Also see: Scleroderma and Pregnancy) |
| Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. In this large cohort of RA patients, the most heightened risk of serious infections was seen with the use of glucocorticoid agents and immunosuppressive DMARDs. Rheumatology. Volume 46, Number 7 Pp. 1157-1160. (Also see: RA) |
| Immune Status and Risk for Infection in Patients Receiving Chronic Immunosuppressive Therapy. Patients receiving chronic immunosuppressive therapy can develop severe lymphopenia that involves all subsets. Monitoring T-helper cell counts may be useful to estimate the risk for subsequent infections in such patients. J Rheumatol. 2005 August;32:1473-80. |
| Chemo Brain |
| Some immunosuppressants are chemotherapy drugs, but used at higher dosages than when used to treat autoimmune disease. |
| Chemobrain: When cancer treatment disrupts your thinking and memory, Dealing with thinking and memory problems caused by cancer or cancer treatment can be frustrating. Find out more about chemobrain and how to cope. MayoClinic. |
| Scientists Find 'Chemo Brain' No Figment Of The Imagination. People with 'chemo brain' often can't focus, remember things or multitask the way they did before chemotherapy. ScienceDaily. 10/08/06. |
