Is It Still Inflammation? Save

A 34 year old female has axSpA. Her CRP is 3, her MRI is quiet, and her BASDAI is 7. She has tried two biologics and is asking about a third. Before we write that prescription, #ACR26 challenges us to ask a different question: is it still inflammation?

A third is not a minority

The Oregon group combined the Fibromyalgia Survey Questionnaire (FSQ) with quantitative sensory testing in 83 patients meeting ASAS criteria [1337]. Nociplastic features were present in 32.5%. FSQ scores correlated with lower pressure pain thresholds at every site tested, from trapezius to sacroiliac joint to knee (r 0.47 to 0.60), and with ASDAS CRP (r 0.53). Female sex was strongly associated (OR 14), which matters because women with axSpA already wait longer for diagnosis and are more often labelled as having fibromyalgia instead. Interestingly, temporal summation and conditioned pain modulation did not differ between groups, so the signal lay in widespread tenderness rather than in every dynamic pain test. One in three is not a minority and is a clinical phenotype we may meet in every clinic.

A six item screen

A second study found fibromyalgia in 9.3% of 151 SpA patients [1354]. Those affected had an ASDAS CRP of 3.7 against 2.2, and markedly worse function and quality of life. The six item Fibromyalgia Rapid Screening Tool (FiRST) questionnaire had a negative predictive value of 98.4%, so a negative screen largely rules fibromyalgia out. The authors conclude to screen routinely, or there may be a risk of escalating treatment for symptoms that are not driven by inflammation. A further poster links altered brain connectivity to pain and disease burden in axSpA [1332], a reminder that this is biology, not imagination, and that the brain is part of the disease experience rather than a separate diagnosis.

Early relief tells us something

The UPSTAND study looked at pain from the other direction [0347]. Patients on upadacitinib whose back pain improved by at least 30% after one week had higher odds at one year of ASDAS low disease activity (OR 2.21) and BASDAI below 4 (OR 3.98), with better fatigue and function. A week is too short for inflammation in bone and enthesis to resolve, so part of this signal may be analgesic, and part may identify pain that is mostly inflammatory and therefore responsive. The analysis is post hoc. The early response is feasible to measure and easy to act on.

The arithmetic of composite scores

ASDAS and BASDAI both depend on what patients tell us. That is their strength, because they capture what matters to people, and their weakness, because they cannot distinguish nociceptive from nociplastic pain. A score of 7 can mean active sacroiliitis, central sensitisation, poor sleep or all three. Treating a target only works if we know what we are targeting.

The ASAS points to consider for difficult to manage axSpA, list nociplastic pain and fibromyalgia first among the mimics to exclude before declaring treatment failure [2944].

Looking beyond the score

How do these approaches change the way we assess our patients? I consider four modest steps to follow. Record a nociplastic screen such as FiRST or FSQ alongside ASDAS. Confirm inflammation with CRP or MRI before escalating. Note how pain responds in the first weeks of a new drug. And offer exercise, sleep and psychological support alongside anti-inflammatories and biologics, not after it fails.

Nociplastic pain is real pain, and it deserves treatment of its own rather than a quiet label in the letter. The aim is to match the treatment to the mechanism. For our axSpA patient, a third biologic may still be right but it should follow evidence of inflammation, not a number alone. Pain in axSpA is a mixture, and the proportions differ between patients. Stratified care begins with knowing the components of the mixture in front of us.