This is an important question. We have one patient with a similar coexistence of the two diseases and treat him with Rituximab every 6 months. he is doing OK with this. Evidence is low for RTX in AS and results from the literature pretty disappointing but I agree that it is difficult to start him on TNF a blockers. Maybe IL17 blockade might be an option, since I am not aware of any neurologic side effects but that's clearly too early to tell. 

Another option might as well be SSZ. It mostly helps for peripheral disease manifestation but there are occasional patients who might benefit for their axial manifestation. Would be worth trying for three months in my view, because you would need to talk to his insurance to cover the costs for rituximab first I guess. 

Hope this helps, Peter

I would advise against using rituximab (I introduced the use of rituximab in RA). There is no theoretical justification for using rituximab in AS because there is no evidence of disturbed B cell function. My understanding is that small trials have confirmed that there is no major efficacy in AS. Similarly there is none in psoriatic disease and there have been reports of both psoriasis and inflammatory bowel disease worsening. Rituximab is not without major adverse reactions - pneumonitis in particular which could be a big problem if there is pulmonary compromise in AS.

All in all I would advise very strongly against.

It happen to have personal interest in such a case.

For AS my approach is based on the work of Alan Ebringer MD:

http://www.springer.com/gp/book/9781447142997

I have get very good results with his starch-free diet, even if it is really difficult for the patients to keep it. Yet, with the benefits that get in most cases about 10-20 days on the diet, than there is strong motivation. For an overview on this approach you can check also this summarizing study:

http://www.hindawi.com/journals/jir/2013/872632/

For MS, I have try a similar approach to support physical rehabilitation in patients under natalizumab treatment, no adverse reaction was observed but I can't say for benefits since the rehabilitation program was quit complex.

Hope you can consider such a strange approach also,

Stergios

I agree with Jonathan, but rituximab has been shown to have some effect on T-cell function as well. But it is true that in the small trials presented, there was no benefit of rituximab in AS. I simply don't know if it might be beneficial for the MS. 

My first try would be SSZ as stated above or IL17 like secukinumab after careful discussion with this young patient. I figure he can't be managed with NSAIDS? How many different NSAIDS has he had as of yet? 

 Dear Dr Peter Korsten,

Rituximab availability is not a problem and can be managed. We don't have Secukinumab in India yet but it is likely to be available in the next few months. The patient has already tried 3 different NSAIDs and is on his third one.

Yes, I will surely try SSZ and wait for IL17 antagonists to come here.

Dear Dr Johnathan Edwards,

Thanks for the cautionary note. I do agree that role of B cell is not clearly delineated in AS. However we are having recent reports on various new antibodies like anti Noggin antibodies, sclerostin-immune complexes, anti CD 74 and anti CLIP antibody having some role in pathogenesis of AS.

This fact combined with being pushed against the wall in this situation and a small ray of hope in the form of the small study in arhritis rheumatism (2010)  that showed a modest response in TNF naive patients (like ours) did make Rituximab look quite attractive.

I will try the approach as mentioned above and wait for some time.

Dear Stergios Tsiormpatzis,

Let me read what you suggest as I have not heard about this and would like to understand the scientific veracity of such an approach before giving it due consideration.

regards

Dear Peter,

I don't think rituximab has been shown to have any relevant effect on T cell function. This is an idea put about by people who work on T cells and like to get grants on T cells but have little or no practical experience with B cell depletion in my experience. It has been going on ever since we developed B cell depletion but never supported by any evidence - the kinetics are wrong, too. I would be interested in any evidence to the contrary - I have not come across it in the last 17 years!!

Rituximab does appear to have a major biological effect in MS in terms of reducing the rate of new lesions. The problem has been with translating that into convincing clinical benefit in trials . There have also been commercial issues about patents I think, so that development has moved to other agents. So far rituximab is not clearly indicated in MS so it does not look a good option on grounds of either condition in this case.

Is there any reason to think SSZ would work? I thought there was no empirical evidence for benefit in axial disease? Anti-IL-17 does seem a logical thing to try but maybe in a formal trial of pure AS before trying it on someone with another condition that might get worse? To my mind the risk here is of major unknowns like PML which would outweigh any off chance of benefit in an isolated case.

Dear Stergios,

The low starch diet idea relates to a hypothesis that I think is now dead and buried. No formal efficacy data were gathered as far as I know. I think we need to base discussion on reliable evidence.

Dear Shankar,

Odd reports about unusual antibodies in AS have been dribbling out for more than twenty five years. As far as I know they have never come to much. The pathology bears no relation to any immune complex mediated process that we know from elsewhere. I would be sceptical.

Dear Jonathan,

Thank you for the interesting comments. I agree with them and there are a lot of good reasons not to try any of the above mentioned medication. But when faced with the question posed, what would your suggestion for treatment of this apparently insufficiently controlled patient be? 

In terms of safety, SSZ seems to be least risky and we have occasional patients who report improvement of axial symptoms with SSZ (and NSAIDs and physical therapy , couse). Clearly, there are no formal reports of improvement in axial manifestations of AS with SSZ.

The trial of secukinumab in AS has just been published but obviously didn't include MS patients. 

http://www.nejm.org/doi/full/10.1056/NEJMoa1505066

Dear Peter,

Thanks for the link to the secukinumab study, which is good to see. I am retired and now work in philosophy so I do not keep up with these things!

My view about patients with no licensed options changed around 1995 when it became clear that rheumatologists needed to do things properly rather than play around the individual patient's health. From then on I only used unlicensed therapies as part of prospective studies that I intended to publish. There are many people with illnesses for which we have no good answers. As doctors I do not think we should meddle with their lives trying out this and that. Now that we have powerful and potentially very toxic medicines we need to be very careful about their use. Even as the person responsible for introducing rituximab into rheumatology I am now responsible for the deaths of a significant number of people, even if a tiny minority. I take that seriously.

Dear Dr Jonathan,

All the suggestions and arguments are very valid. A simple question. What else can I offer to this patient given the current state of evidence?

Thanks

I do not know, Shankar. Perhaps optimism that anti-IL-17 may soon be an option.

Dear Dr Jonathan,

Thank you very much and a very happy new year in advance.

regards

I agree. Rituximab is a very reasonable approach. Certainly would not dream of trying an anti-TNF alpha, but a trial of anti-IL-17 would be reasonable if B-cell-focus does not work after two courses of Rituximab.

Anti-IL-17. . Monitor the Ank Spond closely with the appropriate clinical tools (all the scales available from Bath - BASDAS, BASFI, BASMI- as well as ASDAS) and carefully monitor the MS (consider repeating the MRI even if no clinical change in the clinical status of the MS) and then wait and see. Continue only if sufficient clinical improvement to stop the NSAIDs (Indocin? if not, would ramp up therapy to Indocin)

I suggest anti-IL-17 for both diseases.

This conversation worries me. The internet is a powerful force for good, but also has major dangers. Many sites have grown up where people chat about medical treatments and make suggestions to each other based on no reliable evidence. Since some of these have serious adverse effects it is likely that harm will arise. This is an academic site that ought to steer clear of that and rely on good evidence.

Why would rituximab be reasonable, Leonard? It targets B cells. We have little or no evidence that AS involves B cells and lots of circumstantial evidence for AS and similar conditions (psoriatic etc) showing no benefit or worsening. Rituximab can cause death through PML or pneumonitis. Do you have extensive experience with it - enough hundreds of cases to have encountered a representative sample of problems? Do we have reason, Hsin-Hua, to think anti-IL-17 is safe in the context of MS? Waiting until the PML starts up is not a very reversible strategy.

Are people posting to this site ready to take moral and legal responsibility for their off-hand recommendations? Should we, as responsible physicians, be making statements like this at all? There are plenty of gullible and not so critical people around who will latch on to them - I know from my role in other forums.

Maybe worth thinking about.

Best wishes for 2016.

I would not have predicted B cell-focused therapy would work in psoriatic arthritis and yet there are reports that it does work.  My personal choice would be anti-IL-17 therapy, but if the initial questioner wants to try rituximab it id not an unreasonable approach, not an approach without potential merit. My approach were I the clinician would be indomethacin followed by anti-IL-17 with close monitoring. I am not a great fan of rituximab - too irrevocable in its effect on the B cell repertoire

Dr Subramanian and all contributors,

good morning,

you are facing a real dilemma. At the Montreal Neurological Institute, home of many world leaders in MS clinical and basic research, the AS/MS association is not in their textbook.  We have never seen it in rheumatology in >200 years collective experience.  But, "never say never" as the saying says.  

As you well know by now, if RTX is likely to do little for AS, it is increasingly successfully used in MS and many other CTDs we though were mostly or essentially T cell-mediated (as opposed to B cell-mediated).

You are facing a very unique N=1 clinical context and you cannot base your decision or abstention on published classical RCT of the one-size-fits-all type of design..  Your decision will likely be easier in 10 years when precision P4 or P6 Medicine will be common place with the advent of panomics and systems biology.  

For now, if MS is significant, I would use RTX and may be killing two birds with one stone. 

If MS is not active, I would stick to the basic principle of "Do no harm".  I would collect detailed phenomics/environomics and, do some biobanking for future panomics.  I would buy some time with the usual/unusual AS treatments (excluding anti-TNF but including abatacept and anti-IL17/23).   That being said, a trial of anti-TNF may not be an absolute contraindication, if used under strict supervision and after clear informed consent.  At worse, it will not help MS but will lead into RTX use.

best wishes and thanks for the intellectual stimulation.

Henri Ménard MD, FRCP,, Emeritus Professor, of Medicine, McGill U.

Thank you Dr Menard and everyone else for their valuable inputs.

What is apparent to me is that there is no clear answer out there and I would have to use my own discretion in how best to manage this patient.

As of this month, Secukinumab is available in India. There have been small trials of secukinumab that have shown some benefit in MS. I have decided to procure this agent and give it to this patient. Shall share my experience of patient's response in this forum and possibly later as a publishable case report.

Thanks for all the suggestions

regards