Now that it looks like Rheumatoid Arthritis could be infection driven, the benefits in a study of Clavulin (amoxicilin + clavulanic acid) needs revisiting. It has been know for a long time that certain antibiotics have “anti-inflammatory properties”. Now it might be interpreted that they control bacteria that could augment inflammation. A study of plain amoxicillin did not work.
Does that mean that Clavulin controls this inflammation by having wider antibiotic spectrum and should it engender new respect? Could certain antibiotics work like they do in rheumatoid arthritis and reduce inflammation?
Anti-inflammatories “NSAID’s” work poorly in ankylosing spondylitis. Methotrexate does not seem to help.
Prednisone helps but high dose is needed to get any initial response and cannot be used long-term by self especially related to osteoporosis.
Pamidronate is a game changer in chronic back pains particularly where inflammation is missed. Mixing with prednisone/steroid is possible.
Albert, Hanne B., et al. “Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy.” European Spine Journal 22.4 (2013): 697-707
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631045/
their results were:
Study with just plain amoxicillin 750 mg tid showed NO benefit:
Bråten, Lars Christian Haugli, et al.
Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial.
bmj 367 (2019).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812614/
Antibiotics for Rheumatoid arthritis was discussed here:
Bacteria at Heart of Rheumatoid Arthritis?
Results of three antibiotics are here:
The results look very similar.
A growing quandary has been over the poorly recognized issue of Axial Spondyloarthritis (SpA):
Deodhar, Atul, et al.
Improvement of signs and symptoms of nonradiographic axial spondyloarthritis in patients treated with secukinumab: primary results of a randomized, placebo‐controlled phase III study.”
Arthritis & Rheumatology 73.1 (2021): 110-120.
https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.41477
” Patients with nonradiographic axial SpA do not exhibit definitive radiographic sacroiliitis but have a disease burden comparable to that of patients with AS, including”
Inflammatory back pain (IBP):
- chronic = over 3 months
- insidious onset
- maybe peaking at night or in the morning
- age onset under 40
- predominantly in the pelvis and lower back
- morning stiffness
- nocturnal awakening
- fatigue
- reduced spinal mobility side bending and extension included
- maybe alternating buttock pains
- maybe improved with exercise and worse with rest
- Benefit from NSAID’s/anti-inflammatories
Comment here – response to anti-inflamatories has been used as a golden rule for diagnosis of Ankylosing Spondyliltis but that is a joke because the improvement (change in pain scores) seen doesn’t even reach the 5% needed for statistical significant improvement except with Naproxen which was still only 11.8%
So subjects who say they can’t have inflammatory back pain because arthritis pills did not work are misguided…
———————
Prevalence of nonradiographic axial SpA ~0.1–0.4% – more prevalent in women, and ~16–37% in patients with IBP
Nonradiographic axial SpA has, a slow progression, with diagnostic delays of of 6–8 years.
Radiographic features appear in 10% to 40% of patients over 2–10 years, “with a lifetime risk of progression of ~50%”
Chronic Back pain is associated with elevations of Tumor Necrosis Factor and
Interleukin 6:
Teodorczyk-Injeyan, Julita A., John J. Triano, and H. Stephen Injeyan.
Nonspecific low back pain: inflammatory profiles of patients with acute and chronic pain.
The Clinical journal of pain 35.10 (2019): 818.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735949/
Osteoporosis has recently been found to be a symptom as well in inflammatory Back pain:
Lim, Mie Jin, and Kwi Young Kang.
A contemporary view of the diagnosis of osteoporosis in patients with axial spondyloarthritis.
Frontiers in Medicine 7 (2020): 569449.
https://www.frontiersin.org/articles/10.3389/fmed.2020.569449/full
Could Some cases of chronic low back pain be a version of above inflammatory disease and this is why antibiotics work?
This causes a reconsideration of treatment options:
1) In chronic back pain a trial of antibiotics could be used but in the RA experience it took 3 months to get a drop of two where it would definitely be noticed – so 3 month trial
2) I could not get patients to tolerate clavulin without diarrhea though I had not routinely used loperamide antidiarrheal 2 in AM which might have helped. The antibiotics found useful in RA could be used though obviously amoxicillin is too dumbed-down an antibiotic to be of use ( why do dentists still use it???). Clarithromycin looks promising as well as minocycline.
3) Use of 3 months should be able to see if going to respond but 6 months might be a better length of treatment. Here is the expanded view of individual responses to clavulin and it is clear that significant rebound occurs after the 100 day use:
I had one patient with severe pain from axial spondyloarthritis that was ignored by a rheumatologist. Opioids were only some help and pulses of prednisone had to be used. What I found worked worked well, at least temporarily. was a pamidronate.
Pamidronate has been used in a variety of pain conditions:
I wrote a review about it here:
Pamidronate and Clodronate – hope for Reflex Sympathetic Dystrophy (aka CRPS) and Back Pain
http://painmuse.org/?p=54
It has been found useful in chronic back pain:
Chronic Back Pain May Be a Pamidronate Infusion Treatable Disease – And Why Did It take 10 Years to Replicate That?
http://painmuse.org/?p=3002
Pamidronate 90 mg diluted in 250 mls saline and given over 4 hours – initially and in 4 weeks
and even spinal stenosis:
Pamidronate Works Again in the Back – This Time For the Worst – Spinal Stenosis http://painmuse.org/?p=7723
Ankylosing Spondylitis Use
Most importantly it was found beneficial in ankylosing spondylitis resistant to treatment “refractory”
Maksymowych, W. P., et al. “An open study of pamidronate in the treatment of refractory ankylosing spondylitis.” The Journal of Rheumatology 25.4 (1998): 714-717.
https://europepmc.org/article/med/9558174
60 mg dose once a month for 3 months – at end noted response in 37%
Also helpful in Spinal stenosis:
Feld, Joy, et al.
An open study of pamidronate in the treatment of refractory degenerative lumbar spinal stenosis.
Clinical rheumatology 28.6 (2009): 715-717
https://d1wqtxts1xzle7.cloudfront.net/42278586/An_open_study_of_pamidronate_in_the_trea20160207-29568-1xzpe6w-libre.pdf?1454840832=&response-content-disposition=inline%3B+filename%3DAn_open_study_of_pamidronate_in_the_trea.pdf&Expires=1668384321&Signature=ejnel5vD3Mfzj9QhbHN-TkwbGYerZLY6OEnKxecBg-h2N-lwbmIE7TY66doD68F6dV9neiCDAY~0TTjCU5Hl17jKTM~YApOrTgiTyVyo~RuMx9LkQ6S2lFv1gpjARPjXDQHcWSDyNGIAYkMq5gcoYRBzlZ7wSgSXyC9IQUL7lMG-R6VXNPbfYdUfnf0cNBPe~i4w2HA1FzS1GnqJeeuowMaWQRyQ28Ii6vLxs-N~Di6o-B27sSL9Sjwfx8DnDz3QMKgY69HgHyA6DPZwQAcAUu2TLErl3KSXqz-eRGUWDyFce08TNtVjTU34MREN4PzHL7kyE8qbkZS4fdca3hZFfQ__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
monthly intravenous pamidronate, 60 mg in 500 cc normal saline, over 4 hours
It would allow the use of prednisone as it can build bone even in the presence of this steroid:
Boutsen, Yves, et al.
Primary prevention of glucocorticoid-induced osteoporosis with intermittent intravenous pamidronate: a randomized trial.
Calcified tissue international 61.4 (1997): 266-271.
https://link.springer.com/article/10.1007/s002239900334
- daily doses of prednisone 10 mg
- “30 mg pamidronate, intravenously, every 3 months, for as long as steroid therapy was continued”
- “Over 1 year, the pamidronate group showed a significant BMD (bone density) increase in the lumbar spine (3.6%), and at all sites of the hip (2.2% at the femoral neck).
A another article on Pamidronate showed it helped pain but not inflammatory markers:
Mok, Chi Chiu, et al. “AB0656 Golimumab versus Pamidronate for the Treatment of Axial Spondyloarthropathy (SPA): A 48-Week Randomized Controlled Trial.” Annals of the Rheumatic Diseases 73.Suppl 2 (2014): 1022-1022.
https://ard.bmj.com/content/73/Suppl_2/1022.1.abstract
- PAM (60mg intravenously monthly)
- “patient reported outcomes such as pain score and SF36 improved significantly in both treatment groups.”
Comment :
I am promoting the use of prednisone/pamidronate in axial arthritis back pain though you need good teeth to use latter. If successful, more modern treatments could be used
Severer back pain cases with Modic type 1 could undergo a trial of antibiotics but I think a 3 month trial is necessary to see results and 6 months treatment altogether if response is seen.
This will be an evolving issue and doctors will be slow to pick these up.