Session Information
Date: Sunday, November 8, 2015
Title: Rheumatoid Arthritis - Clinical Aspects I - Treatment Advances and Strategies
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose:
Analysis of long term continuation of biologics in rheumatoid arthritis (RA) is considered a valid surrogate for treatment effectiveness and safety. Only a small number of studies have investigated the long-term persistence with rituximab (RTX) in RA. Analysis of long term continuation of biologics in rheumatoid arthritis (RA) is considered a valid surrogate for treatment effectiveness and safety. Only a small number of studies have investigated the long-term persistence with rituximab (RTX) in RA.
Methods: This analysis included all patients enrolled with the British Society for Rheumatology Biologics Register for RA when starting RTX between 2008 and 2011. Baseline characteristics (demographic, disease and treatment-related data) were compared between bio-naive and experienced cohorts. RTX treatment discontinuation was defined at start of alternative biologic, death or 1 year following the most recent RTX infusion, whichever came first. Kaplan-Meier curves were used to study discontinuation rates over time and by reason, both as a whole cohort and stratified by past biologic treatment experience; discontinuation rates at 1, 2, 3 and 4 years following treatment initiation were ascertained. The association of baseline variables (age, gender, smoking status, presence of comorbidities, disease duration, DAS-28 score, HAQ score, steroid use, methotrexate (MTX) use, previous biologic use) with RTX discontinuation after 4 years was assessed using multivariate Cox-proportional hazards models.
Results: In total, 1629 patients were included (1371 [84.2%] bio-experienced patients and 258 [15.8%] bio-naïve). Bio-experienced patients tended to be younger, but have longer disease duration than bio-naïve patients (Table 1). Treatment persistence at 4 years was 43% (95% CI 40, 45) and was similar between bio-naïve and bio-experienced patients (Figure 1). For the whole cohort, baseline variables associated with RTX discontinuation after 4 years were low DAS28 score (HR 0.91 [95% CI 0.85, 0.98]), RhF negativity (HR 0.84 [0.72, 0.99]) and younger age (HR 0.99 [0.98, 0.99] per year). Higher number of previously used biologics was associated with RTX discontinuation for the bio-experienced cohort (HR 1.28 [CI 1.08, 1.50]) and smoking history was associated for the bio-naïve cohort only (HR 1.82 [1.06, 3.12]). Tocilizumab was the most commonly used subsequent biologic for both the naive and experienced cohorts: 12 (41.4%), 133 (56.8%), respectively.
Conclusion: Just over half of patients were no longer receiving RTX after 4 years, which was similar in both bio-naïve and experienced patients. In bio-experienced patients, those who started RTX after 2 or more past TNFi failures were more likely to discontinue treatment compared to only 1, which may be identifying a more refractory patient cohort. The role of risk factors in predicting treatment outcomes on RTX is again supported by these data.
|
Variable |
All RTX patients n = 1629 |
Biologic naïve patients n = 258 |
Biologic experienced patients n = 1371 |
p-value |
||
|
Mean age/years (SD) |
59.5 (12.1) |
62.5 (11.3) |
58.9 (12.2) |
<0.01 |
||
|
Women, n (%) |
1243 (76.3) |
174 (67.4) |
1069 (78.0) |
<0.01 |
||
|
Current smoker (%) |
226 (13.9) |
56 (21.7) |
170 (12.4) |
<0.01 |
||
|
Comorbidities, n (%) |
0 |
612 (37.6) |
102 (39.5) |
510 (37.2) |
0.53 |
|
|
1 |
518 (31.8) |
77 (29.8) |
441 (32.2) |
0.49 |
||
|
2 |
326 (10.0) |
54 (20.9) |
272 (19.8) |
0.71 |
||
|
3+ |
173 (10.6) |
25 (9.7) |
148 (10.8) |
0.66 |
||
|
ILD, n (%) |
91 (5.6) |
47 (18.2) |
44 (3.2) |
<0.01 |
||
|
Previous TB, n (%) |
64 (3.9) |
10 (3.9) |
54 (3.9) |
0.99 |
||
|
Previous cancer, n (%) |
215 (13.2) |
81 (31.4) |
134 (9.8) |
<0.01 |
||
|
Median disease duration/ years (IQR) |
12 (6, 20) |
10 (4, 20) |
13 (7, 20) |
<0.01 |
||
|
Median DAS28 (IQR) |
6.1 (5.4, 6.8) |
6.1 (5.5, 6.7) |
6.1 (5.4, 6.9) |
0.99 |
||
|
Median HAQ (IQR) |
2.0 (1.6, 2.4) |
1.9 (1.5, 2.3) |
2.1 (1.6, 2.4) |
<0.01 |
||
|
Current steroids, n (%) |
670 (41.1) |
123 (47.7) |
547 (40.0) |
0.02 |
||
|
RhF positive, n (%) |
953 (58.5) |
175 (67.8) |
778 (56.7) |
0.89 |
||
|
Concurrent MTX, n (%) |
247 (15.2) |
233 (90.3) |
1149 (83.8) |
0.01 |
||
|
Leflunomide, n (%) |
129 (7.9) |
27 (10.5) |
102 (7.4) |
0.12 |
||
|
No concurrent DMARD, n (%) |
167 (10.2) |
11 (4.3) |
156 (11.4) |
<0.01 |
||
|
Previous biologics, n (%) |
|
|
|
|
||
|
1 |
|
|
1029 (75.1) |
|
||
|
2 |
|
|
222 (16.2) |
|
||
|
3+ |
|
|
27 (2.0) |
|
||
|
KM estimate after year (95% CI) |
1 |
95 (94, 96) |
95 (93, 98) |
95 (94, 96) |
|
|
|
2 |
71 (69, 73) |
76 (71, 81) |
70 (67, 72) |
|
||
|
3 |
55 (53, 58) |
61 (55, 67) |
54 (52, 57) |
|
||
|
4 |
43 (40, 45) |
44 (38, 51) |
43 (40, 45) |
|
||
|
Median follow-up time in study/ years (IQR) |
4.5 (3.6, 5.4) |
4.5 (3.6, 5.3) |
4.5 (3.6, 5.4) |
|
||
|
Adverse events by 4 years, n (%) |
235 (14.4) |
51 (19.8) |
184 (13.4) |
|
||
|
Inefficacy by 4 years, n (%) |
270 (16.6) |
31 (12.0) |
239 (17.4) |
|
||
|
Started subsequent biologic, n (%) |
263 (16.6) |
29 (11.2) |
234 (17.1) |
|
||
|
No biologic treatment, n (%) |
249 (15.3) |
53 (20.5) |
196 (14.3) |
|
||
To cite this abstract in AMA style:
Oldroyd AGS, Symmons DPM, Kearsley-Fleet L, Watson K, Lunt M, Sergeant J, Hyrich KL. Factors Associated with Long Term Rituximab Use in Rheumatoid Arthritis – Results from the British Society of Rheumatology Biologics Register [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/factors-associated-with-long-term-rituximab-use-in-rheumatoid-arthritis-results-from-the-british-society-of-rheumatology-biologics-register/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-associated-with-long-term-rituximab-use-in-rheumatoid-arthritis-results-from-the-british-society-of-rheumatology-biologics-register/