Aa
To Treat or not. BAD CRYO/Neuro Issues. plz Help
Hello all. New & Confused! HCV Trial interview Fri. & I just do not know what to do! BTHW a person does NOT need to be End Stage to have CRYOGLOBULENEMIA! So, my question and need of feedback is this...should I treat my HCV 1st or my Cryoglobulenemia? Would only HCV all orals kill the cryo too? I am not just Positive for the Cryo but I've been given several special tests including a Quantative (mine is low but it IS there). I know from reading, INF & Riba do great at destroying both the HCV and the Cryo...but I am INF INTOLERANT so that is a closed subject. Looking at triasl cause although new meds are being approved now (ya hoooo) but, for geno 1 (me), it is ONLY WITH the INF.
I have very bad full body Neuropathy, not only in feet and hands but also full torso and face. I also have tremors and muscle weakness...the Cryo is scary bad (as IS this awful HCV)! ! Told symptoms most likely from the Cryo and am on pain meds & anti seizure but it would be great to rid myself of these horrible, horrible diseases. Any and all feedback, comments, finger pointing, and head shaking is all gladly needed. Bless you all. Peace, Health and Blessings, Renee
I have very bad full body Neuropathy, not only in feet and hands but also full torso and face. I also have tremors and muscle weakness...the Cryo is scary bad (as IS this awful HCV)! ! Told symptoms most likely from the Cryo and am on pain meds & anti seizure but it would be great to rid myself of these horrible, horrible diseases. Any and all feedback, comments, finger pointing, and head shaking is all gladly needed. Bless you all. Peace, Health and Blessings, Renee
I've had Cryo flareups in the past along with just about every other joint pain and condition that is known. All of it just goes with the territory of hcv. Luckily the Cryo never got out of control for me. Cryo seemed to be worsen in cold dry winters though. Hcv can really make a person filled with anxiety, all the conditions that run the course you begin to feel like a leaky boat just floating along waiting for the next new thing to come along. I have been trying to get in to a study for the same reason GT 1a (trying to avoid interferon) and it has not been easy, it seems there are long wait lists and the best you can do is to get an interview if you can find one, and get on the wait list. One doctor told me he would put me on the list and gave me good advice "do not refuse any good hcv study that is offered, and do not wait or say I'll get back to you". It seems the three studies I inquired about aren't starting until sometime in January. Neurological pain sounds so familiar, it just gets worse if you can imagine. I'm cryo free but replaced with neuropathy in a few toes and lots of other ailments. I've found several wholeistic remedies to take for now. One is Calms Magnesium with Calcium powder. You just add to 4 ounces hot water and it fizzes up. I take it 2 to 3 times a day and just before bedtime, it put's me right out, sleep the whole night. If something wakes me and I start to feel insomnia, I just have another fizzy drink and back to sleep. It's been giving me pain relief too.
Good luck Renne, don't worry about what to do -just get out there and get on a wait list. The study coordinators know all about hcv and all the chronic conditions that we all have.
Good luck Renne, don't worry about what to do -just get out there and get on a wait list. The study coordinators know all about hcv and all the chronic conditions that we all have.
You should be able to copy all of this. If I am going to copy anything, I just copy and paste it into a Word document. You should be able to copy this entire thread by copying it and pasting it.
Can we not cc This. Just tried to copy your last response and I cd not. Ideas?
Blessings. Renee
Blessings. Renee
I agree about disclosing everything. Another person who had both cryo and is now showing UD for HCV is the one that said not to say anything. As far as my Heptologist ... He is good. Very good. Except that he does not really go out of his way to help find trials AND I don't really think he does a lot Heck, I dona't know how to say this but I really do not think he is concerned about the cryo.
Dr. Gish, an awesome doc who is on Sabatical sent me some info to take to my Rheumatologist. Think I mentioned it but even though all docs are very good, they do not seem to go out of thir area of expertise. Dr. Gish on the other hand is also trying to help but he is not someone I can just pick up the phone and call.
Also...thanx for the info about Phase 3 vs 2. I think again I agree. I do not want a repeat of another bad experience. I am copying the considerations you have listed like the arms etc. I am just not that we'll informed. My Neuropathy has put me in a bad place where it is hard to research.
Bless you for your help.
Dr. Gish, an awesome doc who is on Sabatical sent me some info to take to my Rheumatologist. Think I mentioned it but even though all docs are very good, they do not seem to go out of thir area of expertise. Dr. Gish on the other hand is also trying to help but he is not someone I can just pick up the phone and call.
Also...thanx for the info about Phase 3 vs 2. I think again I agree. I do not want a repeat of another bad experience. I am copying the considerations you have listed like the arms etc. I am just not that we'll informed. My Neuropathy has put me in a bad place where it is hard to research.
Bless you for your help.
That is what I read as well. My thinking is if I can get into a trial (which my hepatologist does not have avail to him) then I can begin getting better.
Would you tell them about the Cryo?
Blessings and Peace. Renee
Would you tell them about the Cryo?
Blessings and Peace. Renee
Thank you so much for the info. My hubby (fast reader) is going through it now.
Should I go for the trial tomorrow? This site has 3 different trials so I don't even know which one. All I know is they are Phase 2. I know, should have gotten the info but I think I was too excited :).
Should I tell them I have the Cryo?
Again, Thank you and Blessings. Renee a/k/a peaceful gal
Should I go for the trial tomorrow? This site has 3 different trials so I don't even know which one. All I know is they are Phase 2. I know, should have gotten the info but I think I was too excited :).
Should I tell them I have the Cryo?
Again, Thank you and Blessings. Renee a/k/a peaceful gal
Often treating the underlying cause of the Cryo , which very often is the HCV will resolve it..
Best of luck..
Will
Best of luck..
Will
Here is a link to another excellent article about HCV and Cryoglobulinemia. It discusses both diseases as well as treatment.
http://www.hindawi.com/journals/cdi/2012/502156/
http://www.hindawi.com/journals/cdi/2012/502156/
Part 4
Whether rituximab should be administered to patients with cryoglobulinemic vasculitis as first- or second-line therapy remains to be determined. On the basis of clinical evidence from uncontrolled and nonrandomized studies, the combination of peginterferon alfa and ribavirin as first-line therapy is recommended for patients with mild-to-moderate disease activity,75,76 although peginterferon alfa may exacerbate some of the clinical features of cryoglobulinemic vasculitis, such as skin ulcers and peripheral neuropathy.16 However, for patients with active disease that is resistant to the antiviral agents, as well as for patients with life-threatening cryoglobulinemic vasculitis, the addition of rituximab or other B-cell–depleting monoclonal antibodies26 can restrain the clonal expansion of a rheumatoid factor–producing B-cell subset.75 This form of triple therapy should be accompanied by plasmapheresis and immunosuppressive therapy. Thus, as a general rule, the choice of the most suitable treatment for a given patient is based strictly on the level of disease activity and the extent and severity of organ involvement16 (Figure 4Figure 4Proposed Therapeutic Algorithm for HCV-Related Cryoglobulinemic Vasculitis (CV), According to Arbitrarily Assessed Disease Activity.).
Persistent or Relapsed Cryoglobulinemic Vasculitis after Successful HCV Treatment
As the duration of follow-up has increased, a new issue has emerged in the treatment of patients with HCV-related cryoglobulinemic vasculitis — namely, the persistence or relapse of cryoglobulinemic vasculitis in spite of a sustained virologic response to antiviral therapy. Levine et al.79 described four patients who had cryoglobulinemic vasculitis despite successful eradication of HCV infection with antiviral therapy. Landau et al.80 reported the clinical features, outcomes, and results of HCV RNA analyses in eight patients with HCV-related cryoglobulinemic vasculitis who had a relapse of vasculitis even though they had a sustained virologic response. Transcription-mediated amplification assays for HCV RNA remained consistently negative in both serum samples and cryoprecipitates. Tests for HCV RNA replication in peripheral-blood mononuclear cells were likewise negative. In most of the patients with relapse, the clinical manifestations of cryoglobulinemic vasculitis occurred shortly after discontinuation of antiviral treatment and mainly consisted of purpura and arthralgia, but they either were diminished in intensity or appeared only briefly; in three patients, however, the cryocrit and the clinical manifestations remained unchanged, and a B-cell lymphoma was eventually diagnosed in two of them.
In the typical circulating immune complexes isolated from HCV RNA–positive patients with cryoglobulinemic vasculitis, the virus seems to be the initial inciting agent that triggers the IgG antibody response and, subsequently, the production of a monoclonal IgM component with rheumatoid factor activity.60 However, circulating immune complexes with a different immunochemical structure also can be envisaged in patients who are still positive for anti-HCV antibodies but have become negative for HCV RNA after antiviral therapy and who continue to have clinical and immunologic features of cryoglobulinemic vasculitis. How should these patients be treated? Since they are negative for HCV RNA, there is no reason to administer antiviral therapy. An obvious alternative would be to use low or medium doses of glucocorticoids, perhaps eventually turning to cyclophosphamide, rituximab, or ofatumumab,26 a humanized CD20 monoclonal antibody that targets an epitope distinct from the one recognized by rituximab.
Additional Therapeutic Approaches to Cryoglobulinemic Vasculitis
In addition to the already established dual and triple combinations of antiviral drugs, new categories of direct-acting antiviral agents (Figure 3) are under preclinical and clinical development. Novel biologic agents are also being developed for the treatment of cryoglobulinemic vasculitis. A short description of these incomplete and rapidly changing therapeutic approaches is provided in the Supplementary Appendix.
Double-Filtration Plasmapheresis
Therapeutic apheresis, a procedure generally performed for palliative purposes, can be useful in the treatment of patients with cryoglobulinemic vasculitis who have a hyperviscosity syndrome.16 The underlying rationale is the possibility of removing both the cryoprecipitating proteins and the viral particles. Although multicenter, randomized studies comparing plasma exchange with either placebo or immunosuppressive therapy are still lacking,81 strikingly positive results have been reported.82,83 In particular, double-filtration plasmapheresis allows the selective removal of pathogenic substances from plasma while preserving other, essential components.83 In our patients with cryoglobulinemic vasculitis who have inveterate, indolent leg ulcers, double-filtration plasmapheresis has resulted in progressive scarring and eventual complete wound healing. Candidates for double-filtration plasmapheresis are patients with late, refractory-stage cryoglobulinemic vasculitis, as well as those with earlier disease stages. The procedure can be used alone or in combination with antiviral therapy.
Conclusions
Our understanding of the cause and pathophysiology of HCV-related cryoglobulinemic vasculitis has progressed considerably in the past 15 to 20 years. Although improvements in treatment have also been made, only rarely is disease resolution achieved. The introduction of new antiviral protease inhibitors, new triple-therapy or even quadruple-therapy combinations, and new B-cell–depleting or B-cell–modulating monoclonal antibodies, as well as the possibility of using interferon-free regimens, will expand the panorama of treatment options for chronic HCV infection84 and, consequently, HCV-related cryoglobulinemic vasculitis, making it possible to individualize the choice of therapy combinations according to the patient's treatment history and HCV genotype.
Whether rituximab should be administered to patients with cryoglobulinemic vasculitis as first- or second-line therapy remains to be determined. On the basis of clinical evidence from uncontrolled and nonrandomized studies, the combination of peginterferon alfa and ribavirin as first-line therapy is recommended for patients with mild-to-moderate disease activity,75,76 although peginterferon alfa may exacerbate some of the clinical features of cryoglobulinemic vasculitis, such as skin ulcers and peripheral neuropathy.16 However, for patients with active disease that is resistant to the antiviral agents, as well as for patients with life-threatening cryoglobulinemic vasculitis, the addition of rituximab or other B-cell–depleting monoclonal antibodies26 can restrain the clonal expansion of a rheumatoid factor–producing B-cell subset.75 This form of triple therapy should be accompanied by plasmapheresis and immunosuppressive therapy. Thus, as a general rule, the choice of the most suitable treatment for a given patient is based strictly on the level of disease activity and the extent and severity of organ involvement16 (Figure 4Figure 4Proposed Therapeutic Algorithm for HCV-Related Cryoglobulinemic Vasculitis (CV), According to Arbitrarily Assessed Disease Activity.).
Persistent or Relapsed Cryoglobulinemic Vasculitis after Successful HCV Treatment
As the duration of follow-up has increased, a new issue has emerged in the treatment of patients with HCV-related cryoglobulinemic vasculitis — namely, the persistence or relapse of cryoglobulinemic vasculitis in spite of a sustained virologic response to antiviral therapy. Levine et al.79 described four patients who had cryoglobulinemic vasculitis despite successful eradication of HCV infection with antiviral therapy. Landau et al.80 reported the clinical features, outcomes, and results of HCV RNA analyses in eight patients with HCV-related cryoglobulinemic vasculitis who had a relapse of vasculitis even though they had a sustained virologic response. Transcription-mediated amplification assays for HCV RNA remained consistently negative in both serum samples and cryoprecipitates. Tests for HCV RNA replication in peripheral-blood mononuclear cells were likewise negative. In most of the patients with relapse, the clinical manifestations of cryoglobulinemic vasculitis occurred shortly after discontinuation of antiviral treatment and mainly consisted of purpura and arthralgia, but they either were diminished in intensity or appeared only briefly; in three patients, however, the cryocrit and the clinical manifestations remained unchanged, and a B-cell lymphoma was eventually diagnosed in two of them.
In the typical circulating immune complexes isolated from HCV RNA–positive patients with cryoglobulinemic vasculitis, the virus seems to be the initial inciting agent that triggers the IgG antibody response and, subsequently, the production of a monoclonal IgM component with rheumatoid factor activity.60 However, circulating immune complexes with a different immunochemical structure also can be envisaged in patients who are still positive for anti-HCV antibodies but have become negative for HCV RNA after antiviral therapy and who continue to have clinical and immunologic features of cryoglobulinemic vasculitis. How should these patients be treated? Since they are negative for HCV RNA, there is no reason to administer antiviral therapy. An obvious alternative would be to use low or medium doses of glucocorticoids, perhaps eventually turning to cyclophosphamide, rituximab, or ofatumumab,26 a humanized CD20 monoclonal antibody that targets an epitope distinct from the one recognized by rituximab.
Additional Therapeutic Approaches to Cryoglobulinemic Vasculitis
In addition to the already established dual and triple combinations of antiviral drugs, new categories of direct-acting antiviral agents (Figure 3) are under preclinical and clinical development. Novel biologic agents are also being developed for the treatment of cryoglobulinemic vasculitis. A short description of these incomplete and rapidly changing therapeutic approaches is provided in the Supplementary Appendix.
Double-Filtration Plasmapheresis
Therapeutic apheresis, a procedure generally performed for palliative purposes, can be useful in the treatment of patients with cryoglobulinemic vasculitis who have a hyperviscosity syndrome.16 The underlying rationale is the possibility of removing both the cryoprecipitating proteins and the viral particles. Although multicenter, randomized studies comparing plasma exchange with either placebo or immunosuppressive therapy are still lacking,81 strikingly positive results have been reported.82,83 In particular, double-filtration plasmapheresis allows the selective removal of pathogenic substances from plasma while preserving other, essential components.83 In our patients with cryoglobulinemic vasculitis who have inveterate, indolent leg ulcers, double-filtration plasmapheresis has resulted in progressive scarring and eventual complete wound healing. Candidates for double-filtration plasmapheresis are patients with late, refractory-stage cryoglobulinemic vasculitis, as well as those with earlier disease stages. The procedure can be used alone or in combination with antiviral therapy.
Conclusions
Our understanding of the cause and pathophysiology of HCV-related cryoglobulinemic vasculitis has progressed considerably in the past 15 to 20 years. Although improvements in treatment have also been made, only rarely is disease resolution achieved. The introduction of new antiviral protease inhibitors, new triple-therapy or even quadruple-therapy combinations, and new B-cell–depleting or B-cell–modulating monoclonal antibodies, as well as the possibility of using interferon-free regimens, will expand the panorama of treatment options for chronic HCV infection84 and, consequently, HCV-related cryoglobulinemic vasculitis, making it possible to individualize the choice of therapy combinations according to the patient's treatment history and HCV genotype.
Part 3
Antigen-Driven B-Cell Proliferation and Therapeutic Deletion of B-Cell Clonalities
Clonal expansions of IgM rheumatoid factor–producing B cells in HCV-positive patients with mixed cryoglobulinemia have been reported since 1995.56 HCV RNA genomic sequences have been detected and quantified in intrahepatic B cells isolated from patients with chronic HCV infection, some of whom have had type II mixed cryoglobulinemia.57 Intrahepatic B cells have been shown to be capable of spontaneously synthesizing rheumatoid factors that display a major cross-reactive idiotype, designated WA.58 This finding suggests a direct role for HCV in sustaining an in situ B-cell expansion59,60 that preferentially involves rheumatoid factor–producing cells.
Consequently, the deletion of B-cell clonalities may provide a rational approach to treatment. It is well known that CD20 antigen, a transmembrane protein, is selectively expressed on pre-B and mature lymphocytes and that CD20-positive cells are expanded and activated in patients with cryoglobulinemic vasculitis.61-63 Therefore, it was logical to propose the use of rituximab, a chimeric monoclonal antibody specifically directed against CD20 antigen, to treat patients with HCV-related cryoglobulinemic vasculitis that was refractory to conventional antiviral therapy or patients who have had a relapse of disease after therapy.
We evaluated a regimen of four weekly intravenous infusions of rituximab (375 mg per square meter of body-surface area) in 20 patients with HCV-related cryoglobulinemic vasculitis that was resistant to interferon alfa therapy.19 This strategy resulted in a complete response of clinical and laboratory signs — that is, a reduction in the serum cryoglobulin level and a significant decrease in rheumatoid factor and in anti-HCV antibody titers — in 80% of the patients; in 75% of these patients, the remission was sustained throughout 12 months of follow-up. In addition, a marked depletion or even disappearance of peripheral-blood B-cell clones was observed in the patients with a response. However, rituximab treatment caused a transient increase in HCV RNA levels, whereas levels of alanine aminotransferase were mostly unchanged (Fig. 1S in the Supplementary Appendix, available with the full text of this article at NEJM.org). Although the increased viral load decreased within a few months, and liver enzyme levels were not significantly affected,64 close monitoring of these measures is warranted.65
Zaja et al.20 administered the above-described rituximab treatment together with medium-to-low doses of glucocorticoids in 12 patients with HCV-related mixed cryoglobulinemia. Clinical symptoms, as well as low-grade non-Hodgkin's lymphoma (occurring in 3 of the patients), significantly improved in most of these patients, and a complete response was achieved in 1 patient with membranoproliferative glomerulonephritis. Furthermore, the serum cryoglobulin level significantly decreased, and the viral load remained stable in most of the patients.
In a randomized clinical trial involving 24 patients with HCV-associated cryoglobulinemic vasculitis who had not had a response to treatment with interferon alfa and ribavirin or who had had unacceptable side effects with this treatment, 12 patients were randomly assigned to receive rituximab at the above-mentioned dosage, and the remaining 12 continued to receive maintenance or increased immunosuppressive therapy.66 At study month 6, a total of 83% of the patients in the group receiving rituximab had a complete response, as compared with 8% in the control group. Both cryoglobulin levels and the viral load decreased significantly in the rituximab group. De Vita et al.67 conducted a long-term, randomized clinical trial involving 59 patients with cryoglobulinemic vasculitis in whom antiviral therapy had been unsuccessful or was contraindicated. In one group, patients were randomly assigned to receive two 1-g infusions (on days 0 and 14) of rituximab, with retreatment on the same schedule at relapse; the other group received conventional treatment (glucocorticoids, azathioprine or cyclophosphamide, or plasmapheresis). The proportion of patients who continued taking their assigned therapy at 12 months, which was the primary end point of the study, was significantly higher in the rituximab group (64.3%, vs. 3.5% in the conventional-treatment group); the difference remained significant at 24 months. Rituximab also decreased global disease activity. The median duration of the response to rituximab for all three target-organ manifestations (skin ulcers, active glomerulonephritis, and peripheral neuropathy) was 18 months. Changes in the HCV RNA load were not assessed. When patients in the conventional-treatment group who did not have a response were switched to the rituximab group, 61% of them had a response to treatment.
A lower dose of rituximab (250 mg per square meter given twice 1 week apart)68 was shown to be equally effective. In a study involving 23 HCV-positive patients with cryoglobulinemic vasculitis that was refractory to antiviral therapy, the overall response rate (79%) and side effects were similar to those observed with the higher dosage in the above-described study.19 Cryoglobulin levels were lowest at month 12 after rituximab administration in patients with a clinical response, and there was no increase in the viral load.
Additional studies69-72 have addressed the issue of whether rituximab should be used, either alone or in combination with glucocorticoids or antiviral therapy. Because of the marked heterogeneity of these investigations in terms of study design, HCV genotype, previous treatment, rituximab dose, and concomitant therapy (Table 1S in the Supplementary Appendix), the results are not directly comparable and should therefore be considered with caution. Nevertheless, taken together, the findings support the efficacy, safety, and acceptable side-effect profile of rituximab in the treatment of patients with cryoglobulinemic vasculitis that is resistant to, or that relapses after, antiviral therapy.
In a study assessing the addition of rituximab to peginterferon alfa and ribavirin in order to improve response rates, the triple-drug regimen was administered to 22 HCV-positive patients with cryoglobulinemic vasculitis for 48 weeks; 15 additional patients with the same disease received peginterferon alfa and ribavirin without rituximab.73 Follow-up proceeded for 36 months after the end of treatment. Among patients treated with the triple-drug regimen, the complete-response rate was 54.5%; among those who received peginterferon alfa plus ribavirin without rituximab, the rate was only 33.3% (P<0.05). Even more interesting were the following observations: in the large majority of patients with a response to the triple-drug regimen (83%), a conversion of B-cell populations from oligoclonal to polyclonal was identified by clonal analysis of B cells from the liver, bone marrow, and peripheral-blood compartments; in all patients who received the triple-drug regimen, the complete response was maintained throughout the follow-up period, whereas this was the case in only 40% of the patients in the control group; and no increase in the viral load was observed in patients who received the triple-drug regimen.
A similar prospective cohort study74 showed that the addition of rituximab to peginterferon alfa and ribavirin resulted in a shorter time to complete clinical remission, greater efficacy with respect to renal involvement, a higher rate of cryoglobulin disappearance, and more effective clonal B-cell suppression, as compared with peginterferon alfa and ribavirin alone.
Antigen-Driven B-Cell Proliferation and Therapeutic Deletion of B-Cell Clonalities
Clonal expansions of IgM rheumatoid factor–producing B cells in HCV-positive patients with mixed cryoglobulinemia have been reported since 1995.56 HCV RNA genomic sequences have been detected and quantified in intrahepatic B cells isolated from patients with chronic HCV infection, some of whom have had type II mixed cryoglobulinemia.57 Intrahepatic B cells have been shown to be capable of spontaneously synthesizing rheumatoid factors that display a major cross-reactive idiotype, designated WA.58 This finding suggests a direct role for HCV in sustaining an in situ B-cell expansion59,60 that preferentially involves rheumatoid factor–producing cells.
Consequently, the deletion of B-cell clonalities may provide a rational approach to treatment. It is well known that CD20 antigen, a transmembrane protein, is selectively expressed on pre-B and mature lymphocytes and that CD20-positive cells are expanded and activated in patients with cryoglobulinemic vasculitis.61-63 Therefore, it was logical to propose the use of rituximab, a chimeric monoclonal antibody specifically directed against CD20 antigen, to treat patients with HCV-related cryoglobulinemic vasculitis that was refractory to conventional antiviral therapy or patients who have had a relapse of disease after therapy.
We evaluated a regimen of four weekly intravenous infusions of rituximab (375 mg per square meter of body-surface area) in 20 patients with HCV-related cryoglobulinemic vasculitis that was resistant to interferon alfa therapy.19 This strategy resulted in a complete response of clinical and laboratory signs — that is, a reduction in the serum cryoglobulin level and a significant decrease in rheumatoid factor and in anti-HCV antibody titers — in 80% of the patients; in 75% of these patients, the remission was sustained throughout 12 months of follow-up. In addition, a marked depletion or even disappearance of peripheral-blood B-cell clones was observed in the patients with a response. However, rituximab treatment caused a transient increase in HCV RNA levels, whereas levels of alanine aminotransferase were mostly unchanged (Fig. 1S in the Supplementary Appendix, available with the full text of this article at NEJM.org). Although the increased viral load decreased within a few months, and liver enzyme levels were not significantly affected,64 close monitoring of these measures is warranted.65
Zaja et al.20 administered the above-described rituximab treatment together with medium-to-low doses of glucocorticoids in 12 patients with HCV-related mixed cryoglobulinemia. Clinical symptoms, as well as low-grade non-Hodgkin's lymphoma (occurring in 3 of the patients), significantly improved in most of these patients, and a complete response was achieved in 1 patient with membranoproliferative glomerulonephritis. Furthermore, the serum cryoglobulin level significantly decreased, and the viral load remained stable in most of the patients.
In a randomized clinical trial involving 24 patients with HCV-associated cryoglobulinemic vasculitis who had not had a response to treatment with interferon alfa and ribavirin or who had had unacceptable side effects with this treatment, 12 patients were randomly assigned to receive rituximab at the above-mentioned dosage, and the remaining 12 continued to receive maintenance or increased immunosuppressive therapy.66 At study month 6, a total of 83% of the patients in the group receiving rituximab had a complete response, as compared with 8% in the control group. Both cryoglobulin levels and the viral load decreased significantly in the rituximab group. De Vita et al.67 conducted a long-term, randomized clinical trial involving 59 patients with cryoglobulinemic vasculitis in whom antiviral therapy had been unsuccessful or was contraindicated. In one group, patients were randomly assigned to receive two 1-g infusions (on days 0 and 14) of rituximab, with retreatment on the same schedule at relapse; the other group received conventional treatment (glucocorticoids, azathioprine or cyclophosphamide, or plasmapheresis). The proportion of patients who continued taking their assigned therapy at 12 months, which was the primary end point of the study, was significantly higher in the rituximab group (64.3%, vs. 3.5% in the conventional-treatment group); the difference remained significant at 24 months. Rituximab also decreased global disease activity. The median duration of the response to rituximab for all three target-organ manifestations (skin ulcers, active glomerulonephritis, and peripheral neuropathy) was 18 months. Changes in the HCV RNA load were not assessed. When patients in the conventional-treatment group who did not have a response were switched to the rituximab group, 61% of them had a response to treatment.
A lower dose of rituximab (250 mg per square meter given twice 1 week apart)68 was shown to be equally effective. In a study involving 23 HCV-positive patients with cryoglobulinemic vasculitis that was refractory to antiviral therapy, the overall response rate (79%) and side effects were similar to those observed with the higher dosage in the above-described study.19 Cryoglobulin levels were lowest at month 12 after rituximab administration in patients with a clinical response, and there was no increase in the viral load.
Additional studies69-72 have addressed the issue of whether rituximab should be used, either alone or in combination with glucocorticoids or antiviral therapy. Because of the marked heterogeneity of these investigations in terms of study design, HCV genotype, previous treatment, rituximab dose, and concomitant therapy (Table 1S in the Supplementary Appendix), the results are not directly comparable and should therefore be considered with caution. Nevertheless, taken together, the findings support the efficacy, safety, and acceptable side-effect profile of rituximab in the treatment of patients with cryoglobulinemic vasculitis that is resistant to, or that relapses after, antiviral therapy.
In a study assessing the addition of rituximab to peginterferon alfa and ribavirin in order to improve response rates, the triple-drug regimen was administered to 22 HCV-positive patients with cryoglobulinemic vasculitis for 48 weeks; 15 additional patients with the same disease received peginterferon alfa and ribavirin without rituximab.73 Follow-up proceeded for 36 months after the end of treatment. Among patients treated with the triple-drug regimen, the complete-response rate was 54.5%; among those who received peginterferon alfa plus ribavirin without rituximab, the rate was only 33.3% (P<0.05). Even more interesting were the following observations: in the large majority of patients with a response to the triple-drug regimen (83%), a conversion of B-cell populations from oligoclonal to polyclonal was identified by clonal analysis of B cells from the liver, bone marrow, and peripheral-blood compartments; in all patients who received the triple-drug regimen, the complete response was maintained throughout the follow-up period, whereas this was the case in only 40% of the patients in the control group; and no increase in the viral load was observed in patients who received the triple-drug regimen.
A similar prospective cohort study74 showed that the addition of rituximab to peginterferon alfa and ribavirin resulted in a shorter time to complete clinical remission, greater efficacy with respect to renal involvement, a higher rate of cryoglobulin disappearance, and more effective clonal B-cell suppression, as compared with peginterferon alfa and ribavirin alone.
Part 2
Renal function should be evaluated in all patients before ribavirin is administered for the treatment of cryoglobulinemic vasculitis. Patients with a creatinine clearance of less than 50 ml per minute and those undergoing hemodialysis are not eligible for treatment. Patients with renal impairment should be monitored for the development of hemolytic anemia, and the daily dose of ribavirin should be adapted to the glomerular filtration rate.41 If the serum creatinine level increases to more than 2.0 mg per deciliter (177 μmol per liter), therapy with peginterferon alfa and ribavirin must be discontinued. Whether ribavirin can be replaced with one or more of the new direct-acting antiviral agents, which do not require dose adjustment in patients with chronic renal disease,42,43 has not been established.
Several host and viral factors predictive of a poor response or no response to peginterferon alfa and ribavirin have been identified — namely, obesity, hepatic steatosis, insulin resistance, alcohol consumption, drug abuse, advanced age, male sex, African-American ethnic background, high viral load, advanced liver fibrosis, and infection with HCV genotype 1 or 4. 44 Moreover, gene-expression profiling performed on liver-biopsy specimens obtained before therapy has shown the up-regulation of a specific set of interferon-stimulated genes in patients with treatment-resistant disease.44,45 In addition to the modification of factors susceptible to correction (e.g., obesity, alcohol consumption, and drug abuse), the identification of conditions associated with low response rates qualifies these patients for treatment with the combination of peginterferon alfa, ribavirin, and the new direct-acting antiviral agents, possibly preceded by a 4-week lead-in period of therapy with peginterferon alfa and ribavirin only.
At least a few of the above-mentioned host and viral factors, and probably additional ones, may also influence the response to treatment and account for the poor prognosis, including death, in some patients with cryoglobulinemic vasculitis. Infections, often exacerbated by immunosuppressive treatments, are now considered to be the most common cause of death in patients with severe and rapidly progressive cryoglobulinemic vasculitis. Conversely, the achievement of a sustained virologic response is invariably associated with marked clinical improvement and significantly reduced mortality.46
Antiviral agents that directly target specific viral functions are now available for the treatment of patients infected with HCV genotype 1.47 Telaprevir and boceprevir have already been approved by the Food and Drug Administration (FDA), and other direct-acting antiviral agents are still under evaluation in phase 1b–3 trials. Telaprevir and boceprevir act as substrates and inhibitors of the hepatic enzyme cytochrome P-450 3A and the drug transporter P-glycoprotein,48 in addition to acting as HCV NS3/4A protease inhibitors.49 Triple therapy consisting of telaprevir or boceprevir with peginterferon alfa and ribavirin has markedly increased the rates of sustained virologic response both among patients who have not previously received treatment and among patients who have not had a response to previous treatment regimens. In two phase 3 trials of these triple-therapy regimens in patients infected with HCV genotype 1 who had not previously received treatment, sustained virologic response rates were 68 to 75% — significantly higher than those obtained with peginterferon alfa and ribavirin alone.50,51 In previously treated patients, however, the extent of prior response to peginterferon alfa and ribavirin was found to strongly influence the effectiveness of triple therapy, with sustained virologic response rates ranging from approximately 30% among patients with no previous response to 85% among patients with a previous response and subsequent relapse.48,52-54
In a preliminary study, 21 patients with chronic HCV genotype 1 infection in whom treatment with peginterferon alfa and ribavirin had failed were randomly assigned to receive 60 mg of daclatasvir (an NS5A replication complex inhibitor) once daily and 600 mg of asunaprevir (an NS3 protease inhibitor) twice daily, either alone (group A) or combined with peginterferon alfa and ribavirin (group B) for 24 weeks.55 Whereas 36% of patients in group A had a sustained virologic response at 12 and 24 weeks after treatment, all patients in group B had a sustained virologic response at 12 weeks, and in 90% of them the response was maintained at 24 weeks after treatment. Thus, the administration of the long-established combination of peginterferon alfa and ribavirin together with new direct-acting antiviral agents seems essential for achieving high rates of sustained virologic response. Furthermore, treatment with interferon-sparing regimens or all-oral interferon-free regimens has also been reported to yield genotype-related high rates of sustained virologic response; after treatment completion, response in these trials was evaluated at 12 weeks, as recently approved by the FDA for HCV drug trials, rather than at 24 weeks.24,25,30
On the basis of the above-mentioned observations on the effective use of triple therapy in patients with chronic HCV infection, it was reasonable to anticipate that a similar regimen in patients with HCV-related cryoglobulinemic vasculitis would be equally effective in increasing the likelihood of a sustained virologic response. However, because patients with cryoglobulinemic vasculitis are often older than 50 years of age, anemia was expected to be an important side effect of combining peginterferon alfa and ribavirin with a direct-acting antiviral agent. This topic has been addressed in a recently published article.22 In an open-label, prospective cohort study, 23 HCV genotype 1–positive patients with cryoglobulinemic vasculitis were treated with the triple-therapy combination of peginterferon alfa and ribavirin with either telaprevir or boceprevir. At week 24, HCV RNA was undetectable in 70% of the patients, and a complete clinical response was achieved in 57% of the patients. In addition, the serum cryoglobulin concentration decreased significantly in conjunction with a significant increase in the C4 complement level. However, a high rate of hematologic side effects (mainly grade 3 and 4 pancytopenia) was recorded. Similar preliminary results have been published in an abstract23 by another group. A cohort of 35 HCV genotype 1–positive patients with cryoglobulinemic vasculitis and advanced liver disease who had not had a response to therapy with peginterferon alfa and ribavirin were treated with the triple-therapy combination of peginterferon alfa, ribavirin, and boceprevir. Patients were assessed at monthly intervals for a mean duration of 34 weeks. Serum cryoglobulin became undetectable in 79% of these patients, and clinical features markedly improved. Side effects were not specified.
Renal function should be evaluated in all patients before ribavirin is administered for the treatment of cryoglobulinemic vasculitis. Patients with a creatinine clearance of less than 50 ml per minute and those undergoing hemodialysis are not eligible for treatment. Patients with renal impairment should be monitored for the development of hemolytic anemia, and the daily dose of ribavirin should be adapted to the glomerular filtration rate.41 If the serum creatinine level increases to more than 2.0 mg per deciliter (177 μmol per liter), therapy with peginterferon alfa and ribavirin must be discontinued. Whether ribavirin can be replaced with one or more of the new direct-acting antiviral agents, which do not require dose adjustment in patients with chronic renal disease,42,43 has not been established.
Several host and viral factors predictive of a poor response or no response to peginterferon alfa and ribavirin have been identified — namely, obesity, hepatic steatosis, insulin resistance, alcohol consumption, drug abuse, advanced age, male sex, African-American ethnic background, high viral load, advanced liver fibrosis, and infection with HCV genotype 1 or 4. 44 Moreover, gene-expression profiling performed on liver-biopsy specimens obtained before therapy has shown the up-regulation of a specific set of interferon-stimulated genes in patients with treatment-resistant disease.44,45 In addition to the modification of factors susceptible to correction (e.g., obesity, alcohol consumption, and drug abuse), the identification of conditions associated with low response rates qualifies these patients for treatment with the combination of peginterferon alfa, ribavirin, and the new direct-acting antiviral agents, possibly preceded by a 4-week lead-in period of therapy with peginterferon alfa and ribavirin only.
At least a few of the above-mentioned host and viral factors, and probably additional ones, may also influence the response to treatment and account for the poor prognosis, including death, in some patients with cryoglobulinemic vasculitis. Infections, often exacerbated by immunosuppressive treatments, are now considered to be the most common cause of death in patients with severe and rapidly progressive cryoglobulinemic vasculitis. Conversely, the achievement of a sustained virologic response is invariably associated with marked clinical improvement and significantly reduced mortality.46
Antiviral agents that directly target specific viral functions are now available for the treatment of patients infected with HCV genotype 1.47 Telaprevir and boceprevir have already been approved by the Food and Drug Administration (FDA), and other direct-acting antiviral agents are still under evaluation in phase 1b–3 trials. Telaprevir and boceprevir act as substrates and inhibitors of the hepatic enzyme cytochrome P-450 3A and the drug transporter P-glycoprotein,48 in addition to acting as HCV NS3/4A protease inhibitors.49 Triple therapy consisting of telaprevir or boceprevir with peginterferon alfa and ribavirin has markedly increased the rates of sustained virologic response both among patients who have not previously received treatment and among patients who have not had a response to previous treatment regimens. In two phase 3 trials of these triple-therapy regimens in patients infected with HCV genotype 1 who had not previously received treatment, sustained virologic response rates were 68 to 75% — significantly higher than those obtained with peginterferon alfa and ribavirin alone.50,51 In previously treated patients, however, the extent of prior response to peginterferon alfa and ribavirin was found to strongly influence the effectiveness of triple therapy, with sustained virologic response rates ranging from approximately 30% among patients with no previous response to 85% among patients with a previous response and subsequent relapse.48,52-54
In a preliminary study, 21 patients with chronic HCV genotype 1 infection in whom treatment with peginterferon alfa and ribavirin had failed were randomly assigned to receive 60 mg of daclatasvir (an NS5A replication complex inhibitor) once daily and 600 mg of asunaprevir (an NS3 protease inhibitor) twice daily, either alone (group A) or combined with peginterferon alfa and ribavirin (group B) for 24 weeks.55 Whereas 36% of patients in group A had a sustained virologic response at 12 and 24 weeks after treatment, all patients in group B had a sustained virologic response at 12 weeks, and in 90% of them the response was maintained at 24 weeks after treatment. Thus, the administration of the long-established combination of peginterferon alfa and ribavirin together with new direct-acting antiviral agents seems essential for achieving high rates of sustained virologic response. Furthermore, treatment with interferon-sparing regimens or all-oral interferon-free regimens has also been reported to yield genotype-related high rates of sustained virologic response; after treatment completion, response in these trials was evaluated at 12 weeks, as recently approved by the FDA for HCV drug trials, rather than at 24 weeks.24,25,30
On the basis of the above-mentioned observations on the effective use of triple therapy in patients with chronic HCV infection, it was reasonable to anticipate that a similar regimen in patients with HCV-related cryoglobulinemic vasculitis would be equally effective in increasing the likelihood of a sustained virologic response. However, because patients with cryoglobulinemic vasculitis are often older than 50 years of age, anemia was expected to be an important side effect of combining peginterferon alfa and ribavirin with a direct-acting antiviral agent. This topic has been addressed in a recently published article.22 In an open-label, prospective cohort study, 23 HCV genotype 1–positive patients with cryoglobulinemic vasculitis were treated with the triple-therapy combination of peginterferon alfa and ribavirin with either telaprevir or boceprevir. At week 24, HCV RNA was undetectable in 70% of the patients, and a complete clinical response was achieved in 57% of the patients. In addition, the serum cryoglobulin concentration decreased significantly in conjunction with a significant increase in the C4 complement level. However, a high rate of hematologic side effects (mainly grade 3 and 4 pancytopenia) was recorded. Similar preliminary results have been published in an abstract23 by another group. A cohort of 35 HCV genotype 1–positive patients with cryoglobulinemic vasculitis and advanced liver disease who had not had a response to therapy with peginterferon alfa and ribavirin were treated with the triple-therapy combination of peginterferon alfa, ribavirin, and boceprevir. Patients were assessed at monthly intervals for a mean duration of 34 weeks. Serum cryoglobulin became undetectable in 79% of these patients, and clinical features markedly improved. Side effects were not specified.
Sorry, that link is not bringing up the full article. I will try to post it here.
Part 1
Therapy for Hepatitis C Virus–Related Cryoglobulinemic Vasculitis
Franco Dammacco, M.D., and Domenico Sansonno, M.D.
N Engl J Med 2013; 369:1035-1045September 12, 2013
Cryoglobulins are immunoglobulins characterized by their insolubility at low temperatures and their dissolution after rewarming.1,2 On the basis of their immunochemical composition, cryoglobulins are classified as either single (type I), consisting of a monoclonal immunoglobulin, or mixed, comprising two or more immunoglobulin isotypes, with (type II) or without (type III) a monoclonal component.3 For many years, mixed cryoglobulinemia was referred to as “essential” because of its undefined cause. In the early 1990s, it became evident that more than 90% of patients with mixed cryoglobulinemia were infected with hepatitis C virus (HCV).4-7 The pathophysiology of mixed cryoglobulinemia, as it is currently understood, is depicted in Figure 1
Cryoglobulins can be detected in 25 to 30% of HCV-positive patients, but in asymptomatic cases, treatment is unnecessary. Cryoglobulin-related illness, known as cryoglobulinemic vasculitis, appears in a minority (10 to 15%) of patients and includes a spectrum of symptoms (Figure 2Figure 2Spectrum of Clinical Features in Patients with HCV-Related Cryoglobulinemic Vasculitis.), ranging in severity from mild (sporadic purpura) to life-threatening.1,2 Consequently, not all patients should be treated to the same extent.16 This review covers both established treatments for HCV-related cryoglobulinemic vasculitis and emerging therapeutic perspectives (Figure 3Figure 3Drugs for the Treatment of HCV-Related Cryoglobulinemic Vasculitis, According to the Therapeutic Target.).
The effectiveness of interferon alfa in the treatment of patients with mixed cryoglobulinemia was observed empirically in 198735; these observations were confirmed and extended in 1991.36 After it was demonstrated that the large majority of patients with cryoglobulinemic vasculitis are HCV-positive,4-7 treatment with interferon alfa became a rational therapeutic strategy, yielding clinical, biochemical, and virologic response in 40 to 60% of cases.37,38 However, this favorable outcome was usually followed by relapse within 6 months after completion of therapy.38
The addition of glucocorticoids to interferon alfa therapy did not significantly increase the percentage of patients with a treatment response,39 although low-to-intermediate doses of glucocorticoids (0.1 to 0.5 mg of prednisone per kilogram of body weight per day), given for weeks or a few months, are believed to mitigate vasculitic flares and to provide symptomatic relief. However, long-term administration of low-dose glucocorticoids (0.1 mg of prednisone per kilogram per day) should be avoided because of their questionable effectiveness and long-term side effects. High doses or pulsed doses of glucocorticoids (1 to 10 mg of prednisone per kilogram) may help to manage severe vasculitic features, including renal and neurologic involvement, and may prevent permanent organ damage.16
The introduction of once-weekly peginterferon alfa combined with the nucleoside antimetabolite ribavirin as therapy for chronic HCV infection resulted in a higher number of sustained virologic responses. This combination is now considered one of the standards of care for the management of HCV infection.40 As expected, the same therapeutic approach was shown to be effective in patients with HCV-related cryoglobulinemic vasculitis. In a preliminary open-label study, treatment with peginterferon alfa and ribavirin resulted in a complete clinical response and sustained virologic response in 7 of 9 patients (78%).17 In another open-label study, 86 patients with cryoglobulinemic vasculitis were treated with peginterferon alfa and ribavirin for 6 or 12 months, depending on the HCV genotype.18 All patients infected with HCV genotype 1 or 4 were given the drug combination for 12 months; only 36% had a sustained virologic response. Of the patients infected with HCV genotype 2 or 3, who underwent 6 months of therapy, 64% had a sustained virologic response. A complete and lasting disappearance of clinical symptoms was recorded in 88% of the patients with a response. Treatment of longer duration (up to 48 weeks for patients infected with HCV genotype 2 or 3 and 72 weeks for patients infected with HCV genotype 1 or 4) has been proposed when improvements in clinical and laboratory measures, but not a complete virologic response, are achieved.16
Next: Part 2
Part 1
Therapy for Hepatitis C Virus–Related Cryoglobulinemic Vasculitis
Franco Dammacco, M.D., and Domenico Sansonno, M.D.
N Engl J Med 2013; 369:1035-1045September 12, 2013
Cryoglobulins are immunoglobulins characterized by their insolubility at low temperatures and their dissolution after rewarming.1,2 On the basis of their immunochemical composition, cryoglobulins are classified as either single (type I), consisting of a monoclonal immunoglobulin, or mixed, comprising two or more immunoglobulin isotypes, with (type II) or without (type III) a monoclonal component.3 For many years, mixed cryoglobulinemia was referred to as “essential” because of its undefined cause. In the early 1990s, it became evident that more than 90% of patients with mixed cryoglobulinemia were infected with hepatitis C virus (HCV).4-7 The pathophysiology of mixed cryoglobulinemia, as it is currently understood, is depicted in Figure 1
Cryoglobulins can be detected in 25 to 30% of HCV-positive patients, but in asymptomatic cases, treatment is unnecessary. Cryoglobulin-related illness, known as cryoglobulinemic vasculitis, appears in a minority (10 to 15%) of patients and includes a spectrum of symptoms (Figure 2Figure 2Spectrum of Clinical Features in Patients with HCV-Related Cryoglobulinemic Vasculitis.), ranging in severity from mild (sporadic purpura) to life-threatening.1,2 Consequently, not all patients should be treated to the same extent.16 This review covers both established treatments for HCV-related cryoglobulinemic vasculitis and emerging therapeutic perspectives (Figure 3Figure 3Drugs for the Treatment of HCV-Related Cryoglobulinemic Vasculitis, According to the Therapeutic Target.).
The effectiveness of interferon alfa in the treatment of patients with mixed cryoglobulinemia was observed empirically in 198735; these observations were confirmed and extended in 1991.36 After it was demonstrated that the large majority of patients with cryoglobulinemic vasculitis are HCV-positive,4-7 treatment with interferon alfa became a rational therapeutic strategy, yielding clinical, biochemical, and virologic response in 40 to 60% of cases.37,38 However, this favorable outcome was usually followed by relapse within 6 months after completion of therapy.38
The addition of glucocorticoids to interferon alfa therapy did not significantly increase the percentage of patients with a treatment response,39 although low-to-intermediate doses of glucocorticoids (0.1 to 0.5 mg of prednisone per kilogram of body weight per day), given for weeks or a few months, are believed to mitigate vasculitic flares and to provide symptomatic relief. However, long-term administration of low-dose glucocorticoids (0.1 mg of prednisone per kilogram per day) should be avoided because of their questionable effectiveness and long-term side effects. High doses or pulsed doses of glucocorticoids (1 to 10 mg of prednisone per kilogram) may help to manage severe vasculitic features, including renal and neurologic involvement, and may prevent permanent organ damage.16
The introduction of once-weekly peginterferon alfa combined with the nucleoside antimetabolite ribavirin as therapy for chronic HCV infection resulted in a higher number of sustained virologic responses. This combination is now considered one of the standards of care for the management of HCV infection.40 As expected, the same therapeutic approach was shown to be effective in patients with HCV-related cryoglobulinemic vasculitis. In a preliminary open-label study, treatment with peginterferon alfa and ribavirin resulted in a complete clinical response and sustained virologic response in 7 of 9 patients (78%).17 In another open-label study, 86 patients with cryoglobulinemic vasculitis were treated with peginterferon alfa and ribavirin for 6 or 12 months, depending on the HCV genotype.18 All patients infected with HCV genotype 1 or 4 were given the drug combination for 12 months; only 36% had a sustained virologic response. Of the patients infected with HCV genotype 2 or 3, who underwent 6 months of therapy, 64% had a sustained virologic response. A complete and lasting disappearance of clinical symptoms was recorded in 88% of the patients with a response. Treatment of longer duration (up to 48 weeks for patients infected with HCV genotype 2 or 3 and 72 weeks for patients infected with HCV genotype 1 or 4) has been proposed when improvements in clinical and laboratory measures, but not a complete virologic response, are achieved.16
Next: Part 2
I am sorry you are having all of these problems. Having HCV is bad enough, but having Cryoblobulinemia adds to the medical problems.
If your Cryglobulinemia was caused by HCV, then you eventually need to eradicate the HCV. I know you said you cannot take Interferon. However, there are new drugs in the pipeline and new drug regimens in the pipeline that would be Interferon free. Unfortunately, it is not clear exactly when these new Interferon free drug regiments will be available. Hopefully some of them will be available by 2015.
However, one can treat the Cryoglobulinemia even if one is not treating the HCV.
Are you seeing a knowledgeable and experienced Rheumatologist as well as a knowledgeable and experienced Hepatologist? Finding knowledgeable and experienced specialists (Rheumatologist and Hepatologist) would be the first step. If it was me, I would try to find these specialists at a University affiliated medical center.clinic. They should be up to date on the most current recommended treatment for your medical situation.
Here is a link to an article in the New England Journal of Medicine. It discusses the treatment of Cryoglobulinemia in HCV positive patients. I know that it discusses the use of Interferon, but keep reading because it eventually gets to a discussion about treating Cryoglobulinemia even when the person is not being treated with Interferon.
A competent Rheumatologist should know how to treat your Cryoglobulinemia even if you cannot take Interferon. Then, when the new Interferon free regimens are approved (or if you can get into a study with the new meds), you will be able to treat the HCV and hopefully eradicate both problems. (Be sure to research any study very well as you really do not want to get into a placebo arm, especially with all of the Cryoglobulinemia related problems you are having.)
http://www.nejm.org/doi/full/10.1056/NEJMra1208642
When you get to the list of selections, pick the following selection, which is at the top of the page:
Therapy for Hepatitis C Virus–Related Cryoglobulinemic Vasculitis ...
www.nejm.org/doi/full/10.1056/NEJMra1208642
by EW Campion - 2013
Wishing you the best. Please stay on the forum and ask questions. This is a good forum and there are many knowledgeable and helpful people on the forum.
If your Cryglobulinemia was caused by HCV, then you eventually need to eradicate the HCV. I know you said you cannot take Interferon. However, there are new drugs in the pipeline and new drug regimens in the pipeline that would be Interferon free. Unfortunately, it is not clear exactly when these new Interferon free drug regiments will be available. Hopefully some of them will be available by 2015.
However, one can treat the Cryoglobulinemia even if one is not treating the HCV.
Are you seeing a knowledgeable and experienced Rheumatologist as well as a knowledgeable and experienced Hepatologist? Finding knowledgeable and experienced specialists (Rheumatologist and Hepatologist) would be the first step. If it was me, I would try to find these specialists at a University affiliated medical center.clinic. They should be up to date on the most current recommended treatment for your medical situation.
Here is a link to an article in the New England Journal of Medicine. It discusses the treatment of Cryoglobulinemia in HCV positive patients. I know that it discusses the use of Interferon, but keep reading because it eventually gets to a discussion about treating Cryoglobulinemia even when the person is not being treated with Interferon.
A competent Rheumatologist should know how to treat your Cryoglobulinemia even if you cannot take Interferon. Then, when the new Interferon free regimens are approved (or if you can get into a study with the new meds), you will be able to treat the HCV and hopefully eradicate both problems. (Be sure to research any study very well as you really do not want to get into a placebo arm, especially with all of the Cryoglobulinemia related problems you are having.)
http://www.nejm.org/doi/full/10.1056/NEJMra1208642
When you get to the list of selections, pick the following selection, which is at the top of the page:
Therapy for Hepatitis C Virus–Related Cryoglobulinemic Vasculitis ...
www.nejm.org/doi/full/10.1056/NEJMra1208642
by EW Campion - 2013
Wishing you the best. Please stay on the forum and ask questions. This is a good forum and there are many knowledgeable and helpful people on the forum.
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Have you discussed all of this with your Hepatologist. He/She knows your condition and should have some insight into what would be best for you.
You definitely need to tell them (the study people) that you have Cryo and anything else that is wrong with you. They need to know as much as possible about you and your health.
As the articles I posted state, the best thing is to get rid of the HCV because then you will probably get rid of the Cryo. However, the articles also state that you can treat the Cryo even if you have not yet gotten rid of the HCV.