Background/Purpose:

Previously
it was shown that non-steroidal antiinflammatory drugs
(NSAIDs) given continuously reduce radiographic progression compared to an on
demand therapy over 2 years in patient with ankylosing
spondylitis (AS). A similar effect was found in an
analysis from a prospective AS cohort (GESPIC). In the current study we tested
whether such an effect of NSAIDs could be confirmed in another prospective
randomized trial.

Methods:

AS patients
were randomized to be treated with either continuous (at least 50% per day of
the maximum dose of 150 mg) or on demand diclofenac for 2 years. Switching to
another NSAID was possible in case of side effects or inefficacy. Eligible patients
had active disease that justified the start or continuation of an NSAID and had
no contraindications for an NSAID therapy. TNF-blockers were not allowed during
the whole study period. Primary outcome was the difference in the increase of
radiographic progression in the spine measured by the mSASSS,
scored by two readers blinded to treatment arm and time point. 

Results:

62 of 85 patients enrolled in the continuous arm (mean age 42 years,
BASDAI 4.2, CRP 8.4 mg/l, disease duration 12.2 y, 74% male, mSASSS 11.3, HLA-B27 positivity 83.5%) and 60 of 82 enrolled
in the on demand arm (mean age 44 years, BASDAI 4.5, CRP 12.9 mg/l, disease
duration 15.2 y, 68% male, mSASSS 14.0, HLA-B27 84%) completed
the study. Surprisingly,
the mSASSS progression was numerically higher in the
continuous group compared to the on demand group (1.28; 95%CI 0.68-1.92 vs 0.79;
95%CI 0.17-1.38 in the completer population), although
this difference was not statistically significant (figure). When only patients were analysed who
were CRP positive at baseline (54% cont., 58% demand) or had syndesmophytes at baseline (55% cont., 57% on demand), both
known risk factors for radiographic progression, again there was numerically a
higher radiographic progression in the continuous vs the on demand group: 1.68
vs 0.83 and 2.1 vs 0.89, respectively. We used the ASAS NSAIDs index (0-100) [3] to quantify NSAIDs intake over the 2 years,
which was 75 (mean) for the continuous and 44 (mean) for the on demand group. At
the end of year 2, 73% of the patients were still on diclofenac and had not switched
to another NSAID.  There were no
differences between the 2 treatment groups regarding
side effects: 19 serious adverse event occurred in the continuous group vs 19
in the on demand group.

Conclusion:

In our
study continuous vs on demand treatment with diclofenac over 2 years did not
prevent radiographic progression in AS. It is highly unlikely that the results
would have been different with a higher number of patients because we found
even a trend for less progression in the on demand group. Since 73% of patients
were still on diclofenac at the end of the study we do
not know whether other NSAIDs such as Celecoxib would
have had a different effect on radiographic progression in our patients.