Name: Bruna Costa da Mata Moura
Type: MSc dissertation
Publication date: 01/04/2019
Advisor:

Name	Role
Valéria Valim Cristo	Advisor *

Examining board:

Name	Role
Valéria Valim Cristo	Advisor *
Valquíria Garcia Dinis	External Examiner *
Vinícius Raphael de Almeida	External Examiner *

Summary: OBJECTIVE: To analyze the survival of immunobiologicals in Rheumatoid Arthritis in
the public network of Espírito Santo.
METHODS: A population-based cohort of 902 patients diagnosed with Rheumatoid
Arthritis with active processes in pharmacies in the state of Espírito Santo, using
biological therapy from January 2010 to April 2017. The Kaplan- Meier and log-rank
were applied. Discontinuation of treatment was considered when the new biological
was started.
RESULTS: At baseline, 84% RA patients were female aged 50-70 years. Anti-TNF
was the main biological agent prescribed as first-line therapy when compared to nonanti-TNF (92.3% vs. 7.5%, p <0.05) in the following proportions: adalimumab (ADA)
40% ( n = 361), infliximab (IFX) 20% (n = 180), etanercept (ETN) 19% (n = 168). The
mean survival for the first biological was 59.61 months (95% CI, 56.69-62.52). ADA
and ETN had better survival compared to IFX (61.64 vs. 60.14 vs 50.06 months, p =
0.01). In the subgroup analysis, the older subjects had a better survival (59 months, p
= 0.036). Overall survival was similar between the anti-TNF and non-anti-TNF groups
(p = 0.517). Rituximab (RTX) showed the best survival compared to non-anti-TNF (59
months, 95% CI, 42.88-75.76, p = 0.01). Twenty-seven percent made the switch to a
second drug. Of these, in 65% (n = 158) the choice was anti-TNF and in 35% (n = 86)
a non-anti-TNF (p <0.05). In this subgroup, ADA (n = 60, 25%) and ETN (n = 57, 23%)
were the main prescription options. The second immunobiologic had a mean survival
of 53.69 months and there was no difference between the groups (anti-TNF vs nonanti-TNF) and each biological therapy (p = 0.412). The non-anti-TNF group was the
most prescribed when compared to anti-TNF (68.63% vs. 31.67%, p <0.05). The most
used drugs were ABA (30%, n = 18) and TOCI (27%, n = 16). The mean survival for
the third biological was 28 months (95% CI, 23.12-33.33), and there was no difference
between the groups and each biological therapy (p> 0.05).
Tocilizumab (TOCI) had the lowest discontinuation rate as the first and second (7%
and 16%) and the lowest among non-TN (13%). The IFX had the highest
discontinuation rate in the first and second line (44% and 50%).
CONCLUSION: In the population with RA and using biological therapy in the state of
Espírito Santo, the anti-TNF group are the most prescribed medications. These
individuals use anti-TNF as the first (92.3%) and second (64%) option, but less
commonly as the third indication (34%). In the first treatment the ADA was the most
prescribed drug, reflecting its accessibility in the SUS, since only the ani-TNF group
were available before 2015. The ADA had the best survival and the IFX had the lowest
survival as first-line therapy, but we had no information on doses and reason for the
interruption. The RTX was the non-anti-TNF with better survival and the TOCI was the
one with the lowest rate of discontinuation. The non-anti-TNF group were the most
prescribed class as third-line therapy reflecting better access after 2015 and prior antiTNF failure. Twenty-seven percent of patients who start an immunobiology fail and
switch to another drug. Prospective studies are needed to compare the survival time
of drugs between biologicals aiming at better public health care planning.
Key words: Rheumatoid arthritis. immunobiologicals. Survival. Discontinuation. AntiTNF. Non anti-TNF.