← Questions/TREATMENT
What if a drug stops working, or never worked?
The short answer
Roughly one in ten people with axial spondyloarthritis still have persistent symptoms after two or more biologics, but only a minority of those are truly resistant to drugs. Fibromyalgia, smoking and pain that is no longer inflammatory account for much of the rest, which changes what the next step should be. With TNF blockers, antibodies against the drug are common and measurable, and some immune-cell patterns during a failed biologic predict whether a switch will work.
7 papers behind this answer, best first
Clicking through to a study? How to read a paper is the ten-minute version.
Difficult-to- manage and treatment refractory axial Spondyloarthritis: Systematic review and meta-analysis of prevalence and determinants.
Autoimmunity reviews
Pooling 11 studies of 5,648 patients, about one in ten people with axial spondyloarthritis have difficult-to-manage disease despite two or more biologics, and the strongest links were fibromyalgia, smoking and carrying HLA-B27. Persistent symptoms often reflect something other than ongoing inflammation, which changes what the next step should be.
Prevalence and clinical factors associated with difficult-to-manage axial spondyloarthritis: a multicentre Italian cohort study with meta-analysis.
Therapeutic advances in musculoskeletal disease
In 252 Italian patients, about 6 percent met the new definition of difficult-to-manage axial spondyloarthritis, persistent disease despite proper treatment, and 3 percent were truly treatment-refractory. Most people whose disease seems stuck are not actually resistant to drugs, which points to other factors, such as pain sensitisation or comorbidity, worth checking before another switch.
What makes axial spondyloarthritis difficult to manage? A qualitative study of patient and rheumatologist perspectives
The Journal of Rheumatology
Interviews with French patients who had been through three or more biologics, and their rheumatologists, found they describe difficult-to-manage disease differently: patients talk about pain, fatigue and what they can no longer do, while doctors talk about not being able to tell inflammation from other causes. Much of what makes AS hard to manage is the conversation itself, not only the biology.
Longitudinal monitoring of adalimumab levels and anti-adalimumab antibodies in Chinese patients with ankylosing spondylitis: a prospective cohort study
Frontiers in Immunology
Tracking 140 Chinese patients on adalimumab (Humira) alone for ankylosing spondylitis, 90 percent developed antibodies against the drug within months, and those with high antibody levels had far lower drug concentrations and roughly half the response rate of those with low levels. Measuring drug and antibody levels in the blood could show early who is heading for treatment failure, and the study sets target concentrations for that.
Reduction of CXCR3+CCR6+ CD4+ T Cells and IL-17+ RORγt+ CD4+ T Cells During Secukinumab Treatment Identifies Patients With Axial Spondyloarthritis Responsive to Subsequent Biologic Therapy.
ACR open rheumatology
Among people who did not respond to secukinumab (Cosentyx), those whose IL-17-producing T cells had fallen during treatment went on to respond to either a higher dose or a switch to a TNF blocker, while those whose cells had not changed failed all three options. A blood test during the first biologic might one day predict whether switching is worth it.
Association between type 2 diabetes and short-term clinical response to TNF inhibitors in patients with ankylosing spondylitis: a propensity score-matched retrospective cohort study.
Clinical rheumatology
In a single-centre study of people with ankylosing spondylitis starting a TNF blocker, those with type 2 diabetes were far less likely to respond in the short term, 20 percent versus 75 percent in the matched comparison. The authors are careful to call it a signal rather than a proof, since blood sugar control and weight were not fully accounted for, but if you have both conditions it is a conversation worth having before judging a drug a failure.
Residual activated Th17 cells during low disease activity are associated with disease worsening in radiographic axial spondyloarthritis: A pilot study.
Joint bone spine
In 21 people with radiographic axial spondyloarthritis whose disease looked quiet, those with more activated Th17 cells still circulating were far more likely to lose control over the next six months; nearly half flared, versus none in the low-Th17 group. Feeling well and having a low score may not mean the inflammatory engine has switched off, and a blood test might one day tell the difference.
Plain-language guides on this from patient organisations
Reviewed sources written for patients. They cover the “what do I do” part that research papers can’t.
- SAA: BASDAI disease-activity calculator ↗
Spondylitis Association of America; a score to take to your rheumatologist
- NASS: Guide to advanced therapies, anti-TNF, IL-17 and JAK (PDF) ↗
National Axial Spondyloarthritis Society (UK)
- NASS: Flares, a practical guide (PDF) ↗
National Axial Spondyloarthritis Society (UK)