| Scleroderma Clinical Trials (MAIN MENU) | |
|
| Scleroderma Clinical Trials: Completed, Negative Results | | | |
| Overview |
| By James R. Seibold, M.D., Chair of ISN Medical Advisory Board. 9-2-03. |
| At present, there are no treatments that are known to change the overall course of systemic types of scleroderma. |
| Recent studies with antifibrotic drugs including D-penicillamine and recombinant human relaxin failed to confirm benefits reported from uncontrolled case series. |
| Immunosuppressive therapies continue to be investigated, including cyclophosphamide, stem cell transplantation and other drugs. |
| Survival has improved dramatically in recent years and is due to the effectiveness of treatments directed at specific internal organ features. These include drugs for pulmonary hypertension (flolan, bosentan) ; renal (kidney) involvement (angiotensin converting enzyme inhibitors) ; and pulmonary (lung) inflammation (cyclophosphamide). |
| Clinical research on scleroderma therapies is currently very active. The choice of therapy is complex and depends on the type of scleroderma (diffuse versus limited) ; the stage of illness (early versus late); and the specific organ-related problems faced by the individual patient. |
| For current treatments and clinical trials, please see: Symptoms and Treatments, and Scleroderma Clinical Trials. |
| The following treatments on this page are either ineffective or unproven for the treatment of scleroderma. |
| Alpha Interferon |
| Systemic sclerosis developing in association with the use of interferon alpha therapy for chronic viral hepatitis. We speculate that the immunomodulatory effects of IFNalpha triggered the clinical manifestations of SSc in this patient. To our knowledge, this is the second case of SSc developing after therapy with IFNalpha and the first in a patient treated for chronic viral hepatitis C. PubMed. Clin Exp Rheumatol. 2004 Sep-Oct;22(5):625-8. (Also see: Causes of Scleroderma: Medications and Liver Involvement) |
| 1998: Alpha Interferon: Study done, no effect on Scleroderma. (1) |
| Anti-TGF-beta Monoclonal Antibodies (CAT 192) |
| Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed. PubMed. Arthritis Rheum. 2007 Jan;56(1):323-33. |
| Anti-TGFß1 Therapy for Diffuse Cutaneous Systemic Sclerosis: a Multicenter, Randomized, Placebo-controlled Phase I/II Trial of CAT-192. Systemic administration of CAT-192 in patients with dcSSc is safe and well tolerated. Modified Rodnan skin score improved more in the 5 or 10 mg/kg subgroups, but this may reflect longer disease duration at baseline. Christopher P. Denton. 1851. ACR 2004. |
| Cambridge Antibody Technology (CAT) has mixed trial results. The UK biotechnology company said the scleroderma treatment was safe and well tolerated, but proved no better at controlling the chronic, life-threatening scarring disorder than an inactive placebo treatment. FDA News 02/10/04. |
| Azathioprine |
| Azathioprine (Imuran ®): No good study on Scleroderma done yet. (1) |
| Chlorambucil |
| Chlorambucil/5-flourouracil - study done, no effect on Scleroderma. (1) |
| Gamma Interferon |
| FDA Public Health Advisory Interferon gamma-1b (marketed as Actimmune). The INSPIRE study of Actimmune for treating idiopathic pulmonary fibrosis (IPF) was stopped because an interim analysis showed that patients with IPF who received Actimmune did not benefit. FDA 03-05-07. |
| No good study yet for Scleroderma. (1) |
| There used to be an article in the Archives of Dermatology, entitled, "Systemic Scleroderma: Multicenter Trial of 1 Year of Treatment With Recombinant Interferon Gamma." |
| Minocycline |
| Scleroderma Clinical Trials: Completed, Negative: Minocycline (Doxicycline) Antibiotic Treatment. This has been proven to be ineffective for the treatment of systemic scleroderma by reliable scientific study. ISN. |
| Penicillamine (Depen) |
| Until very recently, Penicillamine (aka Cuprimine, Depen, or d-penicillamine was commonly used for this purpose in Systemic Scleroderma, but in 1997, a large multi-center clinical trial in the U.S. proved that there was no difference between high-dose and low-dose Penicillamine in the treatment of Scleroderma. |
| This study only tested the difference between high-dose and low-dose. It was not designed to determine if penicillamine is effective in the treatment of Scleroderma, so further studies need to be conducted. |
| Rapid Progression of Scleroderma Possibly Associated with Penicillamine Therapy "...This case raises the possibility that penicillamine may even be harmful in certain patients, and may perhaps be associated with acceleration of the decline in the course of the disease. The mechanism may involve either immune dysregulation or the generation of free radicals, directly toxic to the endothelium and leading to fibrotic tissue repair and intimal thickening." Article was on Medscape.com 1/1/98 (2) |
 A word of caution regarding single-center, retrospective studies. Patients frequently improve on placebo. Patients who are improving usually attribute it to their therapy and thus stay with it. Thus uncontrolled cohorts become enriched for "responders" while failures seek other paths. This dynamic underlies virtually all therapeutic "breakthroughs" which is why large scale double-blinded clinical trials are crucial for determining valid scleroderma treatments. | A retrospective randomly selected cohort study of D-penicillamine treatment in rapidly progressive diffuse cutaneous systemic sclerosis of recent onset. In a population of patients with diffuse cutaneous systemic sclerosis, with progressive disease of recent onset, D-penicillamine treatment at a median dose of 750 mg per day caused a statistically significant reduction in skin involvement and improvement of renal, cardiac and pulmonary involvement. (PubMed) Br J Dermatol. 2008 Feb 16. (Also see: Scleroderma Treatments, and Skin Fibrosis) | |
| Pulmonary-renal syndrome (PRS) in systemic sclerosis: a report of three cases and review of the literature. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy. PubMed. Mod Rheumatol. 2007;17(1):37-44. (Also see: Renal Involvement, Pulmonary Involvement,and Medications) |
| Myasthenia gravis and scleroderma: Two cases and a review of the literature. Myasthenia gravis is uncommon in patients with scleroderma, and when diagnosed is usually associated with previous use of d-penicillamine. Clinically, both myasthenia and scleroderma may present with fatigue, weakness and bulbar symptoms, so one of diagnoses may be delayed. PubMed. Clin Neurol Neurosurg. 2007 Feb 3. (Also see: Myasthenia Gravis) |
| High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial: lessons learned. After analysis, we were not able to tell whether either dose was effective or ineffective. Even in studies that are therapeutically "negative," careful evaluation of the data can examine other hypotheses and thereby provide important insights into other aspects of trial design, outcome measures, patient function, and trial conduct. PubMed. Semin Arthritis Rheum. 2004 Feb;33(4):249-63. |
| Pulmonary involvement in systemic sclerosis due to therapy and as a complication. We report a case of a patient affected by SS, with isolated pulmonary hypertension, who developed bronchiolitis secondary to penicillamine. PubMed. Monaldi Arch Chest Dis. 2005 Jun;63(2):111-3. (Also see: Pulmonary Hypertension) |
| D-Penicillamine Use of D-penicillamine has been associated with a variety of immune-mediated complications including polymyositis, systemic lupus erythematosis, nephritis due to immune complex deposition, scleroderma, and pemphigus. Since the initial reports of penicillamine-related autoimmune MG by Bucknall et al. and Czlonkowska in 1975, over 100 such cases have been documented in the literature. Myasthenia Gravis Foundation of America. |
| Minimal changes nephrotic syndrome associated to penicillamine treatment. We describe three patients with minimal change nephrotic syndrome associated with penicillamine treatment. The drug was stopped and nephrotic syndrome disappeared in 2-4 months, suggesting a possible causal relationship between penicillamine and minimal change disease. PubMed. Nefrologia. 2004;24(2):183-7. |
| Goodpasture-like Syndrome Induced by D-Penicillamine in a Patient with Systemic Sclerosis. This unusual pulmonary-renal syndrome has been described on rare occasions in patients receiving D-penicillamine. This complication appeared to be uniformly fatal unless treated with aggressive immunotherapy. J Rheumatol NO. 7 JULY 2003;30:1616-20 (Also see: Medications) |
| Potaba |
| Study proved no effect on Scleroderma. (1) |
| Quinapril for Scleroderma in Bangor, North Wales, UK |
| Study completed. Quinapril is not effective for scleroderma. |
| Study warns against use of quinapril to treat digital ulcers in cutaneous sclerosis patients. The study concludes that based on these results, the routine use of ACE inhibition in treating upper-limb digital ulcers or other vascular manifestations in patients with systemic sclerosis is not advisable. Dermatology Times E-News. 01/03/08. (Also see: Digital Ulcers and Raynaud's) |
| Relaxin (Recombinant Human Relaxin) |
| Relaxin failed Phase III clinical trials and will not be pursued any further as a treatment for scleroderma. See Relaxin by ISN. |
| Tamoxifen > |
| Open label trial of tamoxifen in scleroderma. Previous reports have suggested that treatment with the selective estrogen antagonist tamoxifen may be effective in diminishing primary and secondary Raynaud's vasospasm, including cases occurring in the setting of scleroderma. Tamoxifen treatment has also been associated with improvement of retroperitoneal fibrosis and desmoid tumors, conditions also associated with abnormal fibroblast proliferation. Tamoxifen increases production of the immunosuppressive cytokine TGF beta which modulates fibroblast activity. The potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised questions about its utility as a therapeutic agent in scleroderma. CONCLUSION: Based on these results, we would not recommend tamoxifen for further large scale studies in scleroderma. PubMed. Clin Exp Rheumatol 2003 Jan-Feb;21(1):99-102 (Also see: Clinical Trials: Ineffective or Unproven) |
| References |
| (1) Source:1998 SF pamphlet "About Medications" |
| Footnotes |
| (2) Medscape requires (free) sign up and password. You do not need to be a medical professional to use Medscape. However this makes for slower access to the site for first-time users. |
| See Also |
| Also see related page, Scleroderma Treatments and Clinical Trials. |
