Kickas.org Forums Treatments, Drugs and Alternatives Anti TNF and other biological medications Anti-Tnf Medication question

Hallo Patrick,
My bloodwork is all normal. But it was normal before I started enbrel. I was loaded on prednisone before the enbrel days, hence no inflammation detected.
And ya, you're right. Biologics are in their own little fancy category.
Enjoy your nearly pain free days!

gday again Amy,

I hope someone is watching who can put this more clearly.. lol.

BRM = anti-TNF & DMARDS - ie. Biological Response Mofifiers.

Both are used for the same conditions just at different stages.

As i said, the need for the DMARD with TNF drugs has been deemed unnecessary in some cases, hence you skipping them i imagine - i was on sulfasalazine & methotrexate prior to Enbrel because the "hoops" you have to jump through down here, to get TNF's requires that they be tried first.

Both are immunosuppressants therefore undermine the immune system leaving us susceptible to infection and other complications but are definitely not the same thing.

Hope this doesnt muddy the waters any further... lol

Patrick

No anything anyone has to offer is always good to know....I have tried to stay off meds, but the last year has kind of rendered me useless without them, so I am having to educate myself on these things.

Nice to hear from you!

Amy:)

Hi Amy,... Here are my thoughts that hopefully won't just muddy things further.

Both Sulfasalasine and Methotrexate are commonly called DMARDS (disease-modifying anti-rheumatic drugs) even though their ability to actually 'modify' the disease progression in AS seems questionable at best. They can help with symptom relief in AS, but symptom relief doesn't mean our spines won't fuse in the end. So, although they're called DMARDS they aren't really modifying the course of progression. DCARTS is probably the better term tho no-one seems to use it as much... (disease controlling anti-rheumatic therapy)... which means they help 'control' symptoms rather that 'modify' the course. Both of these meds work (at least in part) by suppressing the immune system (to keep it from attacking us where it shouldn't.)

(Note to Evelyn , please jump in to correct anything I might've messed up. I'm going on my untrustable memory here. Thanks! )

When you think about it, it's pretty hard with a disease like AS to PROVE whether a medication is actually modifying the course of AS since fusion often takes yearsss++++ to progress. I've been on SSZ for 15 yrs or so, but whether it has modified my disease is anyone's guess. I do have fusion but perhaps I'd have a lot more by now (I'm 44 y/o) if I hadn't taken SSZ. (In my case, I think it's helped.)

To add to the confusion, different countries have different requirements before an AS patient might be given the expensive biologics such as Enbrel, Remicade, or Humira. Some countries require SSZ or MTX to have been tried first (and failed), or to be taken in conjunction with anti-TNF's. In Canada, our Rheumies don't feel there exists enough evidence that either of these meds help enough in treating AS to be worth exposing a patient to the *combined* risk of both. They let patients who are already on these meds continue if starting a biologic, but you aren't required to be on one in the first place.

Biologics are predicted to be *true* DMARDS that will successfully be able to slow progression or perhaps even prevent fusion over the long term. Not sure if they have actually proven this yet or not (as it takes yrs and yrs to prove) but if they haven't yet, they are certainly working on it and believe the potential is promising and exciting! Biologics also act to lower part of the immune system but in a more targeted way than SSZ and MTX (if I understand correctly.)

The bottom line is that our docs here in T.O. generally feel that the biologics are far superior in managing AS, have a better safety profile(!!), and have the best chance to slow or modify the actual course of AS.


As far as cancer risks go regarding the use of biologic meds ~ from what I understand, the risks are microscopically low IN TREATING AS... BUT the jury is still out; they need huge patient populations over longer periods of time, to be sure. So far, the data showing up (in countries that track every single patient) do see a slight notable increase in cancer with Rheumatoid Arthitis patients taking biologics. Apparently, RA patients have a known predisposition for cancer. However, to date this trend is NOT appearing in the AS patient population, according to one Rheumy/researcher I've talked to about this.

I mentioned to her how many of our members here seem concerned about cancer risks re:biologics and she said something I thought was particularly worth repeating, so I really hope I have it right. She said that lowering one's immune system creates, theoretically, an increased risk of cancer since cancer is one thing our immune system works to guard against. BUT she also said what most people don't seem to be aware of to consider is that really high levels of chronic inflammation ALSO increase our risk for getting cancer. So that is something. In the same discussion she explained that anti-TNF's are attempting to lower our over-active immune systems so they are in essence generally trying to bring the system back into balance rather than sink it into the ground. A balance sure sounds nice.


Hugs,
mig

hello again, thanks for all of the info you have kinldy given. I should have maybe said I failed on methotrexate and suplhasalazine, and I have been on predniserone since February - down from 30mg a day to 5 mg a day.
I really appreciate your comments about the cancer risk- yes, it does put it into perspective if the risk is higher with inflammation anyway then surely its better to be out of pain and have lower marker levels. thanks! Jayney

Dear Mig, you described the "disease-modifying" vs. "disease-controlling" point very well, according to my understanding. I'll link directly:
Link to editorial from Journal of Rheumatology
The Concept of Disease Modification in Spondyloarthropathy by HELENA MARZO-ORTEGA, PAUL EMERY, DENNIS McGONAGLE
https://www.kickas.org/modification.shtml
same article is here:
http://www.jrheum.com/subscribers/02/08/1583.html

http://www.ncbi.nlm.nih.gov/entrez/query...t_uids=16932687
Henderson C, Davis JC.
Drug Insight: anti-tumor-necrosis-factor therapy for ankylosing spondylitis.
Nat Clin Pract Rheumatol. 2006 Apr;2(4):211-8.
PMID: 16932687
"...The proinflammatory cytokine tumor necrosis factor (TNF) is central to the pathogenesis of AS. Several anti-TNF drugs have been developed and have been shown to control symptoms effectively, and possibly to prevent both clinical and radiographic progression of disease, in patients with AS...."


http://www.ncbi.nlm.nih.gov/entrez/query...t_uids=16646033
Braun J, Landewe R, Hermann KG, Han J, Yan S, Williamson P, van der Heijde
D; ASSERT Study Group.
Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study.
Arthritis Rheum. 2006 May;54(5):1646-52.
PMID: 16646033
..."CONCLUSION: Patients with AS who received infliximab therapy showed a decrease in spinal inflammation as detected by MRI, whereas those who received placebo showed persistent inflammatory spondylitis."


as for the link between inflammation and cancer - this is a complex relationship, There is evidence for a role of inflammation (and more specifically TNF-alpha) in the development and progression of cancer in certain settings:

http://hum-molgen.org/meetings/meetings/3008.html
Mechanisms Linking Inflammation and Cancer
"...Current thinking is that activated immune cells provide both anti- and pro-tumorigenic signals, thus representing targets to be harnessed or attacked for therapeutic advantage depending upon environmental and/or cellular context..."

medscape article link - medscape requires free registration I believe:

DMARDs in RA
response by Robert I Fox, MD PhD Scripps Memorial Hospital, La Jolla, Californa
http://www.medscape.com/viewarticle/497897
"...The role played by TNF-alpha in both the treatment and pathogenesis of cancer remains less understood.[7] Mounting evidence demonstrates that pathophysiologic concentrations of endogenous TNF-alpha act to promote tumor genesis and growth.[7] Thus, it is difficult to establish a framework for understanding seemingly paradoxical effects of TNF-alpha as both an antitumor agent and a mediator of tumor growth..."

see also:

http://www.cancernetwork.com/journals/oncology/o0202d.htm

http://www.innovations-report.com/html/reports/life_sciences/report-32184.html
cites the following article:
http://medicine.ucsd.edu/Molpath/PDF/Karin_Cancer.pdf

http://www.cancer.gov/think-tanks-cancer-biology/page8

for a discussion of risks of tnf blockers with regard to cancer, with a focus on the recent JAMA article that reported increased lymphoma risk by metaanalysis:
http://arthritis.about.com/od/brms/a/cancerinfection.htm

Mig,

Thanks for the info.....I knew I had read that biologics were DMARDS. Having said that it is rather confusing.

As I said I am currently getting on the Remicade, or going in that study....the jury is still out.

The cancer thing doesn't really scare me, I mean he said no one with AS had actually gotten lymphoma from taking the Remicade....he did say RA patients do have a slightly greater risk.

Anyway, thanks again!

Amy:)

http://www.ncbi.nlm.nih.gov/entrez/query...t_uids=16889756
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G.
Inflammation and cancer: How hot is the link?
Biochem Pharmacol. 2006 Aug 2; [Epub ahead of print]
PMID: 16889756

from text of article:
"...Chronic inflammation has been linked to various steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis [2] and [3]. That inflammation is a risk factor for most type of cancers is now well recognized (Table 1; [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15] and [16])...

...Tumor necrosis factor (TNF-alpha) was first isolated as an anticancer cytokine by our group more than two decades ago [17]. Experience since then has indicated that when expressed locally by the cells of the immune system, TNF-alpha has a therapeutic role. However, when dysregulated and secreted in the circulation, TNF-alpha can mediate a wide variety of diseases, including cancer [17]. TNF-alpha has itself been shown to be one of the major mediators of inflammation [18]. Induced by a wide range of pathogenic stimuli, TNF-alpha induces other inflammatory mediators and proteases that orchestrate inflammatory responses. TNF-alpha is also produced by tumors and can act as an endogenous tumor promoter [18]. The role of TNF-alpha has been linked to all steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis... "

(cited references)


[2] A. Mantovani, Cancer: inflammation by remote control, Nature 435 ( 2005) (7043), pp. 752–753.

[3] L.M. Coussens and Z. Werb, Inflammation and cancer, Nature 420 ( 2002) (6917), pp. 860–867.

[4] C.A. Martey, S.J. Pollock, C.K. Turner, K.M. O’Reilly, C.J. Baglole and R.P. Phipps et al., Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer, Am J Physiol Lung Cell Mol Physiol 287 ( 2004) (5), pp. L981–L991.

[5] R.M. Peek Jr. and J.E. Crabtree, Helicobacter infection and gastric neoplasia, J Pathol 208 ( 2006) ( 2), pp. 233–248.

[6] P.E. Castle, S.L. Hillier, L.K. Rabe, A. Hildesheim, R. Herrero and M.C. Bratti et al., An association of cervical inflammation with high-grade cervical neoplasia in women infected with oncogenic human papillomavirus (HPV), Cancer Epidemiol Biomarkers Prev 10 ( 2001) (10), pp. 1021–1027.

[7] A.M. Di Bisceglie, Hepatitis C and hepatocellular carcinoma, Hepatology 26 (1997) (3 Suppl. 1), pp. 34S–38S.

[8] K. Kanoh, T. Shimura, S. Tsutsumi, H. Suzuki, K. Kashiwabara and T. Nakajima et al., Significance of contracted cholecystitis lesions as high risk for gallbladder carcinogenesis, Cancer Lett 169 ( 2001) (1), pp. 7–14.

[9] B.V. Offersen, M.M. Knap, N. Marcussen, M.R. Horsman, S. Hamilton-Dutoit and J. Overgaard, Intense inflammation in bladder carcinoma is associated with angiogenesis and indicates good prognosis, Br J Cancer 87 ( 2002) (12), pp. 1422–1430.

[10] G. Garcea, A.R. Dennison, W.P. Steward and D.P. Berry, Role of inflammation in pancreatic carcinogenesis and the implications for future therapy, Pancreatology 5 ( 2005) (6), pp. 514–529.

[11] S.J. Murphy, L.A. Anderson, B.T. Johnston, D.A. Fitzpatrick, P.R. Watson and P. Monaghan et al., Have patients with esophagitis got an increased risk of adenocarcinoma? Results from a population-based study, World J Gastroenterol 11 ( 2005) (46), pp. 7290–7295.

[12] B.T. Mossman, D.W. Kamp and S.A. Weitzman, Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers, Cancer Invest 14 (1996) (5), pp. 466–480.

[13] M. Okano and T.G. Gross, From Burkitt's lymphoma to chronic active Epstein-Barr virus (EBV) infection: an expanding spectrum of EBV-associated diseases, Pediatr Hematol Oncol 18 ( 2001) (7), pp. 427–442.

[14] P.A. Vagefi and W.E. Longo, Colorectal cancer in patients with inflammatory bowel disease, Clin Colorectal Cancer 4 ( 2005) (5), pp. 313–319.

[15] M. Berwick, B.K. Armstrong, L. Ben-Porat, J. Fine, A. Kricker and C. Eberle et al., Sun exposure and mortality from melanoma, J Natl Cancer Inst 97 ( 2005) (3), pp. 195–199.

[16] W.G. Nelson, A.M. De Marzo, T.L. DeWeese and W.B. Isaacs, The role of inflammation in the pathogenesis of prostate cancer, J Urol 172 ( 2004) (

[17] B.B. Aggarwal, Signalling pathways of the TNF superfamily: a double-edged sword, Nat Rev Immunol 3 ( 2003) (9), pp. 745–756.

[18] F. Balkwill, Tumor necrosis factor or tumor promoting factor?, Cytokine Growth Factor Rev 13 ( 2002) ( 2), pp. 135–141.

Hi Mig, Thanks for that. You just have a talent for explaining it all so well! Care to help me with my thesis? (The most painful part of my day, these days!)
Have a great day!

gday folks ..

well thats exactly what i said .. kinda .. sorta ..
thanks for the full explain mig & evelyn - some serious reading there.

Hope the days are good .. we're finally getting some rain.. yay

Patrick